Avelumab (MSB0010718C; anti-PD-L1) in combination with axitinib as first-line treatment for patients with advanced renal cell carcinoma
Abstract
TPS4580 Background: Targeted agents have improved outcomes in advanced renal cell carcinoma (aRCC), but patients (pts) inevitably develop resistance. Programmed death-1 receptor ligand (PD-L1) is a key therapeutic target in the reactivation of the immune response against multiple cancers, including RCC. Avelumab* is a fully human IgG1 anti-PD-L1 antibody showing clinical activity in several tumor types. Axitinib is a receptor tyrosine kinase inhibitor (TKI) indicated for treatment of aRCC after failure of one prior systemic therapy; axitinib also shows clinical activity as a first-line (1L) therapy. In recent trials, anti-PD-1/TKI combinations have shown promising clinical efficacy in aRCC, and preliminary data suggest better tolerability for the combination with axitinib. This open-label, multicenter, dose-finding study (NCT02493751) evaluates the novel combination of avelumab + axitinib as 1L therapy in pts with aRCC. Methods: The primary objective for this global phase Ib study is to assess safety and tolerability of avelumab + axitinib, defined by dose-limiting toxicities, and determine the maximum tolerated dose (MTD). Eligibility criteria include: histologically confirmed aRCC with a clear cell component, archival or fresh tumor biopsy, ECOG PS 0-1, no prior immunotherapy, and no prior systemic therapy for aRCC. Up to 55 pts will receive avelumab (10 mg/kg or 5 mg/kg as a 1h IV infusion Q2W) + axitinib (5 mg or 3 mg orally BID) in dose-finding and dose-expansion parts and treatment will be given until confirmed disease progression, unacceptable toxicity, withdrawal, or study termination. Other objectives include assessment of objective tumor response (RECIST 1.1), disease control, progression-free survival, OS, duration of response, time to response, pharmacokinetics, pharmacodynamics, immunogenicity, tumor tissue biomarkers, and safety (NCI-CTCAE v4.03). Enrollment began in Oct 2015. A phase 3 trial of avelumab + axitinib vs sunitinib monotherapy as 1L treatment of aRCC is planned. *Proposed INN. Clinical trial information: NCT02493751.
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In contrast to sunitinib, the addition of avelumab to axitinib could enhance progression-free survival in patients with advanced renal cell carcinoma.
“In contract to Sunitinib, an FDA-approved receptor tyrosine kinase inhibitor, the addition of avelumab to Axitinib could enhanced progression free survival (PFS) in these patients [67].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [67]
Avelumab in combination with axitinib is currently regarded as first-line therapy for patients with advanced renal cell carcinoma.
“Furthermore, Avelumab, in combination with Axitinib, is currently regarded as first-line therapy for patients with advanced renal cell carcinoma (RCC) [66,67].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [67]
Cited by
Sorted by citations
Immune Checkpoint Inhibitors in Cancer Therapy
Shiravand, Y., Khodadadi, F., Kashani, S. M. A., Hosseini-Fard, S. R., Hosseini, S., Sadeghirad, H., Ladwa, R., O’Byrne, K., & Kulasinghe, A. (2022) · Current Oncology · doi:10.3390/curroncol29050247 · Cited by 1,353 · see citing works
“In contract to Sunitinib, an FDA-approved receptor tyrosine kinase inhibitor, the addition of avelumab to Axitinib could enhanced progression free survival (PFS) in these patients [67].”
BackgroundInfluentialCombination therapy with immune checkpoint inhibitors (ICIs); a new frontier
Vafaei, S., Zekiy, A. O., Khanamir, R. A., Zaman, B. A., Ghayourvahdat, A., Azimizonuzi, H., & Zamani, M. (2022) · Cancer Cell International · doi:10.1186/s12935-021-02407-8 · Cited by 278 · see citing works
“Avelumab also in combination with axitinib is now described as first-line treatment for patients with advanced RCC with manageable safety profile and substantial tolerability [111, 118].”
BackgroundAvelumab: First Global Approval
Kim, E. (2017) · Drugs · doi:10.1007/s40265-017-0749-6 · Cited by 132 · see citing works
“JAVELIN Renal 100 (NCT02493751) is an open-label, multicentre, phase Ib trial that examines the use of intravenous avelumab with oral axitinib as first-line therapy in patients with advanced renal cell carcinoma [39].”
Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer
Kuusk, T., Albiges, L. K., Escudier, B. J., Grivas, N., Haanen, J. B. A. G., Powles, T. B., & Bex, A. (2017) · Angiogenesis · doi:10.1007/s10456-017-9550-0 · Cited by 69 · see citing works
“For example, axitinib was further investigated in a phase Ib study which evaluated the safety, pharmacokinetics and pharmacodynamics of axitinib (3 or 5 mg twice a day) in combination with the antiPD-L1 inhibitor avelumab (10 mg/kg every 2 weeks) in first-line advanced RCC [40].”
Jochéms, C., Hodge, J. W., Fantini, M. C., Tsang, K. Y., Vandeveer, A. J., Gulley, J. L., & Schlom, J. (2017) · International Journal of Cancer · doi:10.1002/ijc.30767 · Cited by 50 · see citing works
Prognostic impact of PD-1 and its ligands in renal cell carcinoma
Erlmeier, F., Weichert, W., Schrader, A. J., et al. (2017) · Medical Oncology · doi:10.1007/s12032-017-0961-y · Cited by 25 · see citing works
Sergio Bracarda, A., Porta, C., Sabbatini, R., & Rivoltini, L. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.07.009 · Cited by 12 · see citing works
Hurwitz, M. E., Sokhn, J., & Petrylak, D. P. (2016) · Current Opinion in Urology · doi:10.1097/mou.0000000000000345 · Cited by 10 · see citing works
“Patients who progress on arms 1 and 2 can cross over to arm 3 treatment regimen NCT02420821 Atezolizumab Randomized phase III in treatment naı̈ve mRCC with two arms: (1) sunitinib (standard of care); (2) atezolizumabþbevacizumab JAVELIN Renal 100 NCT02493751 Avelumab Phase Ib/II of avelumabþaxitinib in treatment naı̈v…”
BackgroundInfluentialMurali, R., & Gopalakrishnan, A. V. (2023) · Medical Oncology · doi:10.1007/s12032-023-02225-0 · Cited by 6 · see citing works
“Advanced RCC patients are encouraged to use Avelumab and Axitinib as their initial treatment [163, 164] (Table 1).”
BackgroundThe role of COL6A1and PD-1 expressions in renal cell carcinoma
Karabulut, Y. Y., Köse, E. Ç., Bozlu, M., et al. (2020) · Urology Research and Practice · doi:10.5152/tud.2020.20062 · Cited by 5 · see citing works
“Nivolumab and other anti-PD-1, anti-PD-L1 antibodies which are currently in clinical investigation[5-8], are thought to act by modifying the immune response.”
BackgroundSystematic Review on the Efficacy and Safety of Immune Checkpoint Inhibition in Renal Cell Carcinoma
Lyu, C., Li, W., Liu, S., Gao, S., Zhang, H., Hao, L., Yu, H., Wei, W., Song, J., Yang, Y., et al. (2018) · Future Oncology · doi:10.2217/fon-2018-0193 · Cited by 2 · see citing works
Authors, V. (2013) · Current Oncology · doi:10.3747/co.20.1906
Optimising Cancer Immunotherapy: Challenges and Opportunities
Stoddert, T. G. (2016) · European Medical Journal · doi:10.33590/emj/10314662
- Authors
- Larkin, J. M. G., Gordon, M. S., Thistlethwaite, F., Nathan, P. D., Rini, B. I., Martignoni, M., Shnaidman, M., Chiruzzi, C., Di Pietro, A., & Choueiri, T. K.
- Affiliations
- Royal Marsden NHS Foundation Trust (GB)
- HonorHealth (US)
- The Christie Hospital (GB)
- Mount Vernon Cancer Centre (GB)
- Cleveland Clinic (US)
- Pfizer (United States) (US)
- Pfizer, New York, NY;
- Dana-Farber Brigham Cancer Center (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2016-05-20
- Volume
- 34
- Issue
- 15_suppl
- Pages
- TPS4580-TPS4580
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2486936960
- Cited by
- 13
- References
- 0
- Citations by year
- 2023: 1 · 2022: 2 · 2020: 1 · 2018: 2 · 2017: 4 · 2016: 2 · 2013: 1
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- avelumab, axitinib, advanced renal cell carcinoma, PD-L1 inhibitors, first-line therapy, immune checkpoint inhibitors, combination therapy, maximum tolerated dose, dose-limiting toxicity, safety and tolerability, clear cell renal cell carcinoma, sunitinib, immune reactivation
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