Abstract 1084P
Background
Patients (pts) with advanced melanoma that progressed on immunotherapy/targeted therapy have an unmet medical need. Spartalizumab is an anti–PD-1 humanised monoclonal antibody (mAb) that may combine effectively with novel compounds to restore anti-tumour responses in PD-1–refractory disease. This is an analysis of a phase II, randomised, 2-part, multicentre, open-PLATforM (NCT03484923) study in pts with unresectable/metastatic melanoma progressing after prior anti–PD-1/L1 therapy.
Methods
The primary endpoint was overall response rate (ORR) per RECIST v1.1; secondary endpoints included duration of response and biomarker assessments. The selection phase comprised 4 Arms combining spartalizumab with ieramilimab (anti-LAG3 mAb; Arm 1), capmatinib (Arm 2), canakinumab (Arm 3) or ribociclib (Arm 4). An adaptive design during the selection phase allowed dropping arms for futility, adding new arms, and selecting arm(s) for expansion. Bayesian methodology was used for futility and efficacy assessments at each interim analysis (IA).
Results
As of 1 Feb 2021, 175 pts were randomised; 45, 43, 43, and 44 pts in Arms 1-4, respectively. Median age was 59 y, and 57% received ≥2 prior therapies. Overall, 166/175 pts discontinued treatment, primarily due to progressive disease (65%). ORRs in Arms 1-4 were 7% (n = 3/45), 5% (2/43), 5% (2/43) and 7% (3/44), respectively. All arms crossed the specific futility probability threshold and were declared futile at previous IAs. In Arm 1, 6 pts had LAG-3+ melanoma at baseline (≥5% + tumour cells by IHC), of which 2 pts had a partial response, both ongoing for ≈23 months. Overall, grade ≥3 adverse events occurred in 59% of pts (53%, 51%, 36%, 93% in Arms 1-4, respectively). There were 14 on-treatment deaths; 5/45 in Arm 1, primarily due to melanoma progression (4/45).
Conclusions
Although all tested combinations have been declared futile, Arm 1 data suggest pts with LAG-3+ melanoma may be more likely to respond to spartalizumab + ieramilimab treatment. Consequently, Arm 1A (spartalizumab + ieramilimab) was opened and is currently recruiting pts with previously treated unresectable/metastatic LAG-3+ melanoma.
Clinical trial identification
NCT03484923.
Editorial acknowledgement
Medical writing assistance was provided by Sivanjaa Manoj (ArticulateScience), and was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis.
Funding
Novartis.
Disclosure
C. Robert: Financial Interests, Personal, Advisory Role: BMS, Roche, Pierre Fabre, Novartis, Amgen, Sanofi, Merck, MSD, AZ. D. Schadendorf: Financial Interests, Institutional, Funding, Case money for conducting the study to institution: Novartis; Financial Interests, Institutional, Research Grant: Novartis, BMS and Amgen; Financial Interests, Personal, Other, Consulting fees: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Other, Honoraria: Novartis, BMS, Pierre Fabre, Sanofi-Genzyme, Merck-Serono; Financial Interests, Personal, Other, Attending meetings & travel: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Advisory Board: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Leadership Role: Dermatologic Cooperative Oncology Group (DeCOG), German Cancer Society, Hilfe-Stiftung, Deutsche Hautkrebsstiftung, NVKH eV, EuMelaReg. G.V. Long: Financial Interests, Personal, Advisory Role: Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pha; Financial Interests, Personal, Other, Lectures of own work: BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pha. P. Ascierto: Financial Interests, Personal, Research Grant: BMS, Roche Genentech, Array, Sanofi; Financial Interests, Personal, Other, Consultancy fees: BMS, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Medimmune, Sun Pharma, Sanofi, Idera, Sandoz, 4SC, Italfarmaco, Pfizer, Oncosec, Takis, Lunaphore; Financial Interests, Personal, Other, Attending meetings & travel: MSD; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Nektar, Boehringer-Ingelheim, Eisai,; Financial Interests, Personal, Leadership Role: Executive Board of SITC, Steering committee of Society of Melanoma Research, President of Melanoma Foundation, President of Campania Society of Immunotherapy of Cancer.. F. Meier: Financial Interests, Personal, Other, travel support or/and speaker’s fees or/and advisor’s honoraria: Novartis, Roche, Pierre Fabre, MSD, BMS; Financial Interests, Personal, Research Grant: Novartis, Roche. A.A.M. van der Veldt: Financial Interests, Institutional, Other, Consultancy fees: BMS, MSD, Merck, Eisai, Pfizer, Novartis, Pierre Fabre, Roche, Sanofi, Ipsen; Financial Interests, Personal, Other, Attending meetings: Bayer, Pfizer, Roche, Novartis, Ipsen . A. Ribas: Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Advisory Board: Novartis. J.S. Weber: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Personal, Advisory Board: Novartis, BMS, Genentech, GSK, Pfizer, Merck, AstraZeneca, Regeneron; Financial Interests, Personal, Other, Patent owner not used in this study: Biodesix. L. Stenson: Financial Interests, Personal, Full or part-time Employment: Novartis. N. Solovieff: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. A. Louveau: Financial Interests, Personal, Full or part-time Employment: Novartis. A.D. Boran: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. J.J. Grob: Financial Interests, Personal, Other, Consultancy fees: Roche, Novartis, BMS, MSD, Amgen, Pierre Fabre, Sanofi, Merck, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, Amgen, Pierre Fabre, Sanofi, Merck, Pfizer; Financial Interests, Personal, Other, Attending meetings & travel: Roche, Novartis, BMS, MSD, Pierre Fabre,. R. Dummer: Financial Interests, Personal, Advisory Role: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaxiVAX SA, touchIME, ; Financial Interests, Personal, Other, Honoraria: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaxiVAX SA, touchIME. All other authors have declared no conflicts of interest.