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Cited by 9Renal cell carcinoma treatmentCancer Immunotherapy and BiomarkersFerroptosis and cancer prognosis

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Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study.

Open access
Motzer, Robert J., Park, Se Hoon, McDermott, Raymond S., Porta, Camillo, Heng, Daniel Yick Chin, Burotto, Mauricio, Iacovelli, Roberto, Verzoni, Elena, Cutuli, Hernan, Haanen, John, Suárez, Cristina, de Velasco, Guillermo, Valderrama, Begoña P., Westgeest, Hans M., Yuan, Sammy, Perini, Rodolfo F., Wang, Ding, Schmidinger, Manuela·2026·Journal of Clinical Oncology
DOI 10.1200/jco.2026.44.7_suppl.lba417
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Abstract

LBA417 Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti–PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were ≥18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti–PD-(L)1 therapy or ≤6 mo of last dose of adjuvant anti–PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9–39.8) at IA1, and 29.0 mo (19.3–49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0–44.3+) with bel + lenva vs 12.3 mo (1.8+–35.9+) with cabo at IA2. Grade ≥3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti–PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2α inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231 . IA1 IA2 Bel + Lenva, N = 371 Cabo, N = 376 Bel + Lenva, N = 371 Cabo, N = 376 Median PFS (95% CI), mo 14.6 (11.1–16.6) 10.6 (9.2–11.1) 14.8 (11.2–16.6) 10.7 (9.2–11.1) HR (95% CI) 0.74 (0.61–0.89) 0.70 (0.59–0.84) P value (1-sided) .00095* .00007* Median OS (95% CI), mo NR (26.5–NR) 27.4 (23.6–31.4) 34.9 (27.5–NR) 27.6 (24.0–31.4) HR (95% CI) 0.90 (0.70–1.15) 0.85 (0.68–1.05) P value (1-sided) .19322 .06075 ORR, % (95% CI) 52.6 (47.3–57.7) 39.6 (34.6–44.8) 52.6 (47.3–57.7) 40.2 (35.2–45.3) P value (1-sided) .0002* NA NA, not applicable. *Denotes statistical significance.

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TL;DR

In the open-label phase 3 LITESPARK-011 trial, belzutifan plus lenvatinib improved progression-free survival and objective response rate compared with cabozantinib in advanced clear cell renal cell carcinoma after anti–PD-(L)1 therapy. Overall survival favored the combination but did not reach statistical significance at either reported interim analysis, with further follow-up planned.

Key findings

  • Among 747 randomized patients (belzutifan + lenvatinib, n=371; cabozantinib, n=376), median follow-up was 19.6 months at the first interim analysis and 29.0 months at the second.
  • Progression-free survival was significantly longer with belzutifan + lenvatinib: at IA1, median 14.6 vs 10.6 months, HR 0.74 (95% CI 0.61–0.89), one-sided p=.00095; at IA2, median 14.8 vs 10.7 months, HR 0.70 (95% CI 0.59–0.84), one-sided p=.00007.
  • Objective response rate was significantly higher with the combination at IA1: 52.6% vs 39.6%, one-sided p=.0002; at IA2 it was 52.6% vs 40.2%. Median duration of response at IA2 was 23.0 months with belzutifan + lenvatinib vs 12.3 months with cabozantinib.
  • Overall survival did not reach statistical significance: IA1 median not reached vs 27.4 months, HR 0.90 (95% CI 0.70–1.15), one-sided p=.19322; IA2 median 34.9 vs 27.6 months, HR 0.85 (95% CI 0.68–1.05), one-sided p=.06075. Grade ≥3 treatment-emergent adverse events occurred in 84.1% vs 82.7%; treatment-emergent adverse events led to death in 5.4% vs 3.2%, with two vs one treatment-related deaths, respectively.

Methods

  • Open-label, randomized 1:1 phase 3 study (NCT04586231) in patients aged ≥18 years with advanced clear cell renal cell carcinoma that progressed on or after first- or second-line anti–PD-(L)1 therapy, or within 6 months of the last adjuvant anti–PD-(L)1 dose.
  • Patients received belzutifan 120 mg plus lenvatinib 20 mg once daily or cabozantinib 60 mg once daily.
  • Dual primary endpoints were progression-free survival by blinded independent central review per RECIST 1.1 and overall survival. Secondary endpoints included objective response rate (key), duration of response by blinded independent central review, and safety. Results are from interim analyses with data cutoffs of June 26, 2024, and April 9, 2025.

Limitations

  • The paper states no limitations in the provided text.
  • Evident from the text: the overall survival results are from interim analyses and remain immature, with final analysis still pending; the trial is open-label, which may affect safety reporting or other non-blinded assessments; and the authors note that no globally accepted standard of care exists for this post-immunotherapy setting.

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Crossref · 10.1200/jco.2026.44.7_suppl.lba417

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  • Findingown data
    § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 |

    Grade ≥3 treatment-emergent adverse events occurred in 84.1% of patients with belzutifan plus lenvatinib and 82.7% with cabozantinib.

    “Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 |

    Belzutifan plus lenvatinib showed statistically significant improvement in objective response rate versus cabozantinib at IA1 in patients with advanced ccRCC following anti-PD-(L)1 therapy.

    “Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table).”
    • Also stated in: § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 | · boosted
      “Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy.”
    • Also stated in: § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 | · plain
      “| ORR, % (95% CI) | 52.6 (47.3 - 57.7) | 39.6 (34.6 - 44.8) | 52.6 (47.3 - 57.7) | 40.2 (35.2 - 45.3) |”
    Quote in the paperSubstantial claim
  • Findingown data
    § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 |

    In patients with advanced ccRCC progressing after anti-PD-(L)1 therapy, belzutifan plus lenvatinib showed statistically significant improvement in progression-free survival versus cabozantinib at IA1 and IA2.

    “Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table).”
    • Also stated in: § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 | · boosted
      “Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy.”
    • Also stated in: § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 | · plain
      “| Median PFS (95% CI), mo | 14.6 (11.1 - 16.6) | 10.6 (9.2 - 11.1) | 14.8 (11.2 - 16.6) | 10.7 (9.2 - 11.1) |”
    Quote in the paperSubstantial claim
  • Findingown data
    § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 |

    Treatment-emergent adverse events led to death in 5.4% of patients with belzutifan plus lenvatinib and 3.2% with cabozantinib.

    “Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 |

    Median duration of response was 23.0 months with belzutifan plus lenvatinib versus 12.3 months with cabozantinib at IA2.

    “Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2.”
    Quote in the paperNot a substantial claim
  • It may state two separate claims as one. 2
  • The quote only partly states this claim. 1

  • It may state two separate claims as one. The quote only partly states this claim.

    Findingown data
    § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 |

    Overall survival favored belzutifan plus lenvatinib but did not reach statistical significance at IA1 and IA2 in patients with advanced ccRCC following anti-PD-(L)1 therapy.

    “OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing.”
    • Also stated in: § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 | · plain
      “OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis.”
    • Also stated in: § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 | · plain
      “| Median OS | NR (26.5 - NR) | 27.4 (23.6 - 31.4) | 34.9 (27.5 - NR) | 27.6 (24.0 - 31.4) |”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data
    § Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti -PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. Robert J. Motzer, Se Hoon Park, Raymond S. McDermott, Camillo Porta, Daniel Yick Chin Heng, Mauricio Burotto, Roberto Iacovelli, Elena Verzoni, Hernan Cutuli, John Haanen, Cristina Su´ arez, Guillermo de Velasco, Bego ~ na P. Valderrama, Hans M. Westgeest, Sammy Yuan, Rodolfo F. Perini, Ding Wang, Manuela Schmidinger; Memorial Sloan Kettering Cancer Center, New York, NY; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic of; St Vincent ' s University Hospital and Cancer Trials Ireland, Dublin, Ireland; Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy and Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Arthur JE Child Comprehensive Cancer Centre, University of Calgary, Calgary, AB, Canada; Bradford Hill Clinical Research Center, Santiago, Chile; Universit` a Cattolica del Sacro Cuore, Facolt` a di Medicina e Chirurgia, Rome, Italy; Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Hospital Sirio Libanes, Buenos Aires, Argentina; Netherlands Cancer Institute (NKI) Antoni van Leeuwenhoek, Amsterdam; and Leiden University Medical Center, Leiden, Netherlands, Leiden, Netherlands; Vall d´Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain; University Hospital 12 de Octubre, Madrid, Spain; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Amphia Hospital, Breda, Netherlands; Merck & Co., Inc., Rahway, NJ; Medical University of Vienna, Vienna, Austria Background: There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy. VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy. The phase 3 LITESPARK-011 study (NCT04586231) investigates bel + lenva vs cabo in pts with advanced RCC progressing after anti -PD-(L)1 therapy in the 1L, 2L or adjuvant setting. Methods: Eligible pts were $ 18 yrs old with advanced clear cell RCC (ccRCC) that progressed on or after 1L or 2L anti -PD-(L)1 therapy or # 6 mo of last dose of adjuvant anti -PD-(L)1 therapy. Pts were randomized 1:1 to bel 120 mg + lenva 20 mg QD vs cabo 60 mg QD. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1 and overall survival (OS). Secondary endpoints included objective response rate (ORR, key) and duration of response (DOR) by BICR per RECIST 1.1, and safety. Results are reported for the first (IA1; data cutoff Jun 26, 2024) and second (IA2; data cutoff Apr 9, 2025) interim analysis. Results: 747 pts were randomized to bel + lenva (n = 371) or cabo (n = 376). Median (range) follow-up was 19.6 mo (9.9 -39.8) at IA1, and 29.0 mo (19.3 -49.2) at IA2. Bel + lenva showed statistically significant improvement in PFS (IA1, IA2) and ORR (IA1) vs cabo (Table). OS results did not reach statistical significance (Table); additional follow-up for OS is ongoing. Median (range) DOR was 23.0 mo (2.0 -44.3+) with bel + lenva vs 12.3 mo (1.8+ -35.9+) with cabo at IA2. Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively. Conclusions: Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti -PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs. LITESPARK-011 is the first phase 3 study of a HIF-2 a inhibitor combined with a VEGFR-TKI, and the first phase 3 study in RCC to show improved outcomes vs a contemporary VEGFR-TKI. Clinical trial information: NCT04586231. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. | | IA1 | IA1 | IA2 | IA2 |

    Among treatment-emergent adverse event deaths, 2 in the belzutifan plus lenvatinib arm were treatment-related (1 thrombotic microangiopathy and 1 pneumonitis) and 1 in the cabozantinib arm was treatment-related (hemoptysis).

    “Grade $ 3 TEAEs occurred in 84.1% of pts with bel + lenva and 82.7% with cabo; TEAEs led to death in 5.4% of pts (2 were treatment-related: 1 each thrombotic microangiopathy and pneumonitis) and 3.2% of pts (1 was treatment-related: hemoptysis), respectively.”
    Quote in the paperNot a substantial claim
2 of 2

  • The paper relies on this without support.

    There is no globally accepted standard of care for advanced RCC after IO therapy.

    “There is no globally accepted standard of care (SOC) for advanced RCC after IO therapy.”

  • The paper relies on this without support.

    VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy.

    “VEGFR-TKIs are often leveraged in this setting, but were primarily tested in phase 3 studies prior to PD-(L)1 inhibitors becoming SOC in earlier lines of therapy.”
2 of 2

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Metadata

Authors
Motzer, R. J., Park, S. H., McDermott, R. S., Porta, C., Heng, D. Y. C., Burotto, M., Iacovelli, R., Verzoni, E., Cutuli, H., Haanen, J., Suárez, C., de Velasco, G., Valderrama, B. P., Westgeest, H. M., Yuan, S., Perini, R. F., Wang, D., & Schmidinger, M.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Samsung Medical Center (KR)
  • St Vincent’s University Hospital and Cancer Trials Ireland, Dublin, Ireland
  • Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT)
  • University of Calgary (CA)
  • Bradford Hill Clinical Research Center, Santiago, Chile
  • Università Cattolica del Sacro Cuore (IT)
  • Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
  • Hospital Sirio Libanes, Buenos Aires, Argentina
  • Leiden University Medical Center (NL)
  • Vall d'Hebron Hospital Universitari (ES)
  • University Hospital 12 de Octubre, Madrid, Spain
  • Hospital Universitario Virgen del Rocío (ES)
  • Amphia Ziekenhuis (NL)
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
  • Medical University of Vienna (AT)
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2026-03-01
Volume
44
Issue
7_suppl
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2026.44.7_suppl.lba417
OpenAlex
W7133184542
Cited by
9
References
0
Citations by year
2026: 9
Type
conference abstract
Language
en
Open access
Locations
Journal of Clinical Oncology (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
Keywords
belzutifan, lenvatinib, cabozantinib, VEGFR inhibitors, PD-L1 blockade, second-line therapy, progression-free survival, overall survival, objective response rate, duration of response, combination therapy

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