Clinical activity of durvalumab and savolitinib in MET-driven, metastatic papillary renal cancer.
Abstract
4511 Background: Savolitinib is a potent and selective MET inhibitor with activity in MET-driven papillary renal cancer (PRC). Durvalumab is a PD-L1 inhibitor which has been tested in combination with savolitinib in metastatic PRC with response rates of 29% (12/41). Here we describe the efficacy of this combination in MET-driven metastatic PRC. Methods: This single arm phase I/II trial explored durvalumab (1500mg Q4W) and savolitinib (600mg OD) together in metastatic PRC, with a 4wk savolitinib run in. Biomarker analysis results were compared with responses to treatment as planned in the protocol. The analysis presented here focuses on those patients with MET DNA alterations (central analysis:chromosome 7 gain/MET or HGF amplification/MET kinase domain mutations). Confirmed response rate (RR) (RECIST v1.1), progression-free survival (PFS), tolerability (CTCAE v4.03) and overall survival (OS) were analysed. Results: 42 patients were enrolled in the metastatic papillary cohort, of which 41 patients received treatment. The median follow up was 26.8 months. The confirmed RR was 29% (12/41) and median PFS was 4.9 months (95% CI 2.5-10.0). 14/41 (34%) of these patients had MET-driven disease. 71% (10/14) of MET-driven patients had not previously received systemic therapy and 7% (1/14) were PD-L1 positive. IMDC good, intermediate, and poor risk disease occurred in 36% (5/14), 57% (8/14), and 7% (1/14) of MET-driven patients respectively. Confirmed RR in MET-driven patients was 57% (8/14) with duration of response at 9.4 months (95% CI 3.9-Not reached [NR]). Median PFS and OS in MET-driven patients were 10.5 months (95% CI 2.9-15.7) and 27.4 months (95% CI 7.3-NR) respectively. No new safety signals were seen. Conclusions: The combination of savolitinib and durvalumab has clinical activity in MET-driven PRC. A randomised phase III study is planned based upon these data. Clinical trial information: NCT02819596.
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In the phase 2 study NCT02819596, savolitinib plus durvalumab had clinical activity in MET-driven papillary renal cancer (confirmed RR 57%, median PFS 10.5 months, median OS 27.4 months).
“In the phase 2 study NCT02819596, savolitinib (c-MET inhibitor) plus durvalumab had clinical activity in MET-driven papillary renal cancer (Confirmed RR: 57%, median PFS: 10.5 months, median OS: 27.4 months) [242].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [242]
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BackgroundInfluentialThe role of immunotherapy in non-clear cell renal cell carcinoma
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“Although a recently reported phase-II trial also failed to show improved PFS for savolitinib or crizotinib in PRCC [75], another trial (phase-I/II) showed promising results for both durvalumab and savolitinib in METdriven metastatic papillary RCC [77].”
ResultAn Update on the Treatment of Papillary Renal Cell Carcinoma
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“Molecular analysis showed that 14 of the enrolled patients had METdriven disease, in whom the response rate was 57% [52].”
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THE PRECLINICAL JOURNEY OF MET INHIBITORS
Schadt, O., & Dai, G. (2022) · Medicinal chemistry reviews · doi:10.1021/mc-2022-vol57.ch11
- Authors
- Suarez Rodriguez, C., Larkin, J., Patel, P. M., Valderrama, B. P., Rodriguez-Vida, A., Glen, H., Thistlethwaite, F., Ralph, C., Srinivasan, G., Mendez-Vidal, M. J., Carter, A., Tyson, C., Prendergast, A., Mousa, K., & Powles, T.
- Affiliations
- Vall d' Hebron University Hospital, Barcelona, Spain;
- Royal Marsden NHS Foundation Trust (GB)
- Nottingham University Hospitals NHS Trust (GB)
- Hospital Universitario Virgen del Rocío (ES)
- Hospital del Mar, Barcelona, Spain;
- Beatson West of Scotland Cancer Centre (GB)
- University of Manchester (GB)
- University of Leeds (GB)
- Broomfield Hospital (GB)
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, Córdoba, Spain;
- Queen Mary University of London (GB)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2021-05-20
- Volume
- 39
- Issue
- 15_suppl
- Pages
- 4511-4511
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W3169461265
- Cited by
- 14
- References
- 0
- Citations by year
- 2023: 4 · 2022: 6 · 2021: 4
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
- Keywords
- savolitinib, PD-L1 inhibitors, MET inhibitors, combination immunotherapy, MET amplification, MET kinase domain mutations, chromosome 7 gain, progression-free survival, overall survival, treatment safety, biomarker analysis, IMDC risk stratification
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