Abstract 819P
Background
Pts with high tumour burden may benefit from adding anti-PD-1 to targeted therapy.1 Although COMBI-i trial (NCT02967692) did not meet its primary endpoint for overall population, progression-free survival (PFS) was significantly longer with S (anti-PD-1) +DT vs placebo (PBO)+DT in pts with ≥3 metastatic (met) sites (hazard ratio [HR]=0.63; 95% confidence interval [CI] 0.46–0.87).2 This post hoc analysis of COMBI-i examined S+DT vs PBO+DT based on met site.
Methods
In COMBI-i part 3, eligible pts were randomised 1:1 to receive either S+DT (n=267) or PBO+DT (n=265) until progression or unacceptable toxicity.2 Post hoc analysis of PFS and overall survival (OS) was performed in pts with >2/>3 met sites and in pts with adrenal/bone/lung/liver mets at baseline. PFS and OS were summarised descriptively using Kaplan–Meier methods; HRs were estimated using cox regression models.
Results
At data cut off on 01 July 2020, median follow-up for COMBI-i part 3 was 27.2 months.2 Among 531 pts with mets at baseline, n=179 had >2 met sites, n=93 had >3 met sites. Mets at baseline were reported in lung (n=250), liver (n=157), bone (n=57) and adrenal glands (n=33). In pts with >3 met sites, S+DT showed benefit vs PBO+DT in terms of PFS (HR=0.40; 95% CI 0.25–0.65) and OS (HR=0.50; 95% CI 0.28–0.87). Pts with >3 met sites and elevated lactate dehydrogenase (LDH) had longer PFS (HR=0.43; 95% CI 0.24–0.77) and OS (HR=0.42; 95% CI 0.21–0.84) with S+DT vs PBO+DT. Similar results were seen in pts with >2 met sites. PFS was longer with S+DT vs PBO+DT in pts with adrenal (HR=0.20; 95% CI 0.07–0.57), bone (HR=0.45; 95% CI 0.24–0.84) and lung mets (HR=0.59; 95% CI 0.43–0.80); 95% CIs for HR for PFS crossed 1 in pts with liver mets (HR=0.85) or those with isolated lung mets (n=33; HR=1.27).
Conclusions
Pts with >2 or >3 met sites with or without raised LDH derived benefit from adding S to DT, as did pts with lung, bone and adrenal involvement at baseline. Number and site of mets may be a useful guide for patient selection for triplet therapy. 1. Kim et al Front Immunol;11:629722. 2. Dummer et al JCO 2022;JCO2101601.
Clinical trial identification
NCT02967692.
Editorial acknowledgement
The authors thank Olga Ucar of Novartis Pharmaceuticals UK Ltd, London, UK, for providing medical writing assistance.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
P. Nathan: Financial Interests, Personal, Advisory Board: BMS, Immunocore, Novartis, Merck, Pfizer, 4SC; Financial Interests, Institutional, Other, research support: Immunocore; Financial Interests, Personal, Invited Speaker: Novartis, 4SC; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, Ipsen, Immunocore, Merck, Pfizer. J.J. Grob: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Roche, Pierre Fabre, Novartis, Pfizer, Sanofi, Philogen, Iteos Therapeutics, Sunpharma; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Pierre Fabre, Sanofi, Novartis; Financial Interests, Institutional, Research Grant: Pierre Fabre. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaviVAX SA, touchIME, T3 Pharma, Pfizer. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. A. Ribas: Financial Interests, Personal, Advisory Board, Honoraria for consulting: Amgen, Apexigen, AstraZeneca, Merck, Novartis, Sanofi, Vedanta; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: 4C Biomed, Apricity, Arcus, Highlight, Compugen, ImaginAb, MapKure, Merus, Rgenix, Synthekine, Lutris, PACT Pharma, Tango; Financial Interests, Personal, Invited Speaker, Member of the Board of Directors: Arcus, Lutris, PACT Pharma; Financial Interests, Personal, Stocks/Shares, Stock ownership: 4C Biomed, Apricity, Arcus, Highlight, Compugen, ImaginAb, MapKure, Merus, Rgenix, Synthekine, Lutris, PACT Pharma, Tango, Advaxis, CytomX, RAPT, Isoplexis, Kite-Gilead; Financial Interests, Personal, Invited Speaker: Arsenal Bio; Financial Interests, Institutional, Funding: Agilent, Bristol Myers Squibb. C. Robert: Financial Interests, Personal, Advisory Board: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, AstraZeneca, Pfizer. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi, Merck, Novartis, BMS, MSD, 4SC, Nektar; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Roche, Merck Serono, Immunocore, 4SC, Pierre Fabre, Sanofi/Regeneron, Array Biopharma, Pfizer, Philogen, NEKTAR, Sandoz, Neracare; Financial Interests, Institutional, Research Grant: Novartis, BMS, MSD, Array/Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis, BMS, MSD, Pierre Fabre, Sanofi, Roche, Philogen, 4SC, Nektar; Non-Financial Interests, Invited Speaker: EORTC-MG. K.T. Flaherty: Financial Interests, Personal, Other, Consultant: Takeda, Transcode Therapeutics, Novartis; Financial Interests, Personal, Invited Speaker: Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate BioPharma, Scorpion Therapeutics; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate BioPharma, Scorpion Therapeutics, PIC Therapeutics, Apricity, Tvardi, xCures, Monopteros, Vibliome, ALX Oncology, Fog Pharma, Soley Therapeutics; Financial Interests, Personal, Ownership Interest: Nextech; Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Merck, Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. A. Hauschild: Financial Interests, Personal, Advisory Board: BMS, MSD, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi, Novartis, Eisai, Immunocore, Replimune, Seagen; Financial Interests, Personal, Invited Speaker: MerckPfizer; Financial Interests, Institutional, Invited Speaker: BMS, MSD, Pierre Fabre, Amgen, Regeneron, Roche, Novartis. M. Mandala: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre. R. Shah: Financial Interests, Personal, Full or part-time Employment: Novartis. H. Banerjee: Financial Interests, Personal, Full or part-time Employment: Novartis. R.P. Sarkar: Financial Interests, Personal, Full or part-time Employment: Novartis. M.R. Lau: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L.