1888P - 24-month follow up of durvalumab and savolitinib combination in MET-driven clear cell and non-clear cell renal cancer

Background

The CALYPSO trial (NCT02819596) showed promising response rates (RR) for the combination of durvalumab (D) (PD-L1 inhibitor) and savolitinib (S) (MET inhibitor) in MET-driven tumours in papillary renal cancer (PRC). Response data for the combination in other settings such as clear cell (ccRCC) and non-MET driven tumours was less impressive (Suárez et al, JCO, 2023 ). Here we give the updated 24-month efficacy analysis.

Methods

This study included a ccRCC and PRC cohort, both of which have been presented previously with shorter follow up. The ccRCC cohort was a randomised phase II study comparing DS combination with D alone, in previously treated ccRCC. The PRC cohort was a single arm study of DS in treatment naïve or pre-treated patients. RR (confirmed, RECIST 1.1), progression-free survival (PFS) and overall survival (OS) were the efficacy endpoints. DNA alterations were measured using Foundation One analysis.

Results

At 24 months follow-up, the RR in the ITT PRC population (n=41) was 29% (95% CI, 16-46) and 53% (95% CI, 28-77) in MET-driven patients (n=17). The median PFS was 5.8 months (95% CI, 2.9 -12.3) in the ITT population and 15.7 months (95% CI, 3.0 - 27.4) in MET-driven patients. The median OS was 14.1 months (95% CI, 7.3 - 30.7) in the ITT population and 27.4 months (95% CI, 9.3 – 34.7) in MET-driven patients. The hazard ratio (HR) for PFS in MET-driven vs non MET-driven in PRC cohort is 0.43 (95% CI, 0.20-0.93, p=0.03). In the ccRCC cohort, 39 patients received DS combination and 39 D alone. RR for DS was 13% vs 10% for D alone. The HR for PFS was 1.38 (95% CI, 0.5-1.2, p= 0.2) and HR for OS was 1.5 (95% CI, 0.9-2.6, p= 0.1). Median OS was 21.9 months (95% CI, 18.0-26.7) for all ccRCC patients and 8.2 months (3.7- 26.7) for MET-driven patients (n=17). No new safety signals were seen.

Conclusions

Durvalumab and savolitinib combination has activity in MET-driven PRC, supporting the ongoing SAMETA trial (NCT05043090). Savolitinib does not appear to improve efficacy of durvalumab in clear cell tumours.

Clinical trial identification

NCT02819596.

Editorial acknowledgement

Legal entity responsible for the study

Queen Mary University of London.

Funding

AstraZeneca.

Disclosure

C. Suarez Rodriguez: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, BMS (Inst), Ipsen, Pfizer S.L.U, Sanofi- Aventis, Hoffmann-La Roche LTD, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Astellas Pharma, BMS (Inst), Ipsen, Pfizer S.L.U, Hoffmann-La Roche LTD, Merck; Financial Interests, Institutional, Funding: Ipsen. J. Larkin: Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Roche, Pierre Fabre, AstraZeneca, Novartis, EUSA Pharma, MSD, Merck, GSK, Ipsen, Aptitude, Eisai, Calithera, Ultimovacs, Seagen, Goldman Sachs, eCancer, Inselgruppe, Agence Unik; Financial Interests, Personal, Other, Consultancy: Incyte, iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm; Financial Interests, Personal, Other, Honorarium: touchIME, touchEXPERTS, VJOncology, RGCP, Cambridge Healthcare Research, Royal College of Physicians; Financial Interests, Institutional, Funding: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo. B. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, BMS, Ipsen, EUSA Pharma, Merck, MSD, AstraZeneca, AAA; Financial Interests, Personal, Invited Speaker: BMS, Roche, Bayer, EUSA Pharma, MSD, Merck, Pfizer, Janssen, Astellas Pharma, AAA. A. Rodriguez-Vida: Financial Interests, Personal, Invited Speaker: Roche, BMS, Janssen, AstraZeneca Ipsen; Financial Interests, Personal, Advisory Board: MSD, Pfizer, Astellas, Bayer, Merck. M.J. Mendez Vidal: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Ipsen, Astellas, Pfizer, Merck, Sanofi, Eisai, Bayer; Financial Interests, Personal, Invited Speaker: BMS, Ipsen, Roche, Astellas, Merck, Bayer; Non-Financial Interests, Other, Travel expenses: Ipsen, BMS. A. Markovets, R.J. Hartmaier: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. B.E. Szabados: Financial Interests, Personal, Other, travel funding: Roche/Genentech; Financial Interests, Personal, Invited Speaker: MSD, Pfizer; Financial Interests, Personal, Advisory Board: Ellipses, Merck KGaA, Ipsen. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. All other authors have declared no conflicts of interest.