1106P - NivoLag-when: International real-world study of combination immunotherapy sequences in melanoma

Background

Three immune checkpoint inhibitor (ICI) regimens are standard of care in metastatic melanoma (MM): anti-PD1 combined with anti-CTLA4 (ipi/nivo), with anti-LAG3 (rela/nivo) or as monotherapy. Data describing the efficacy of sequential regimens are limited.

Methods

This multicenter retrospective and prospective study assessed patients (pts) who received rela/nivo followed by ipi/nivo (A); ipi/nivo followed by rela/nivo (B); or anti-PD1 followed by rela/nivo (C). Primary endpoint was objective response rate (ORR) to second treatment (Tx). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety.

Results

With a median follow-up of 62.5 months (mo), 130 pts (A=26; B=43; C=61) from Europe, USA and Australia were included. Favorable baseline characteristics were observed in C, with lower prevalence of stage M1c-d (26.3%) compared with A (88.4%) and B (67.5%) and fewer pts with high LDH (14.8%) compared with A (46.2%) and B (32.6%). In C, 12 pts had received anti-PD1 as adjuvant Tx, of which 8 were primary resistant (PRes), as defined by the SITC (Kluger JITC 2020). B had more pretreated pts with ≥2 lines in 44.2%, vs 7.7% in A and 8.2% in C. ORR were 15.4%, 19% and 26.8% in A, B and C respectively. ORR were numerically lower in PRes to prior Tx than for secondary resistance (SRes) in A and B. In C, ORR was 33.4% (95% CI 9.9-65.1) for pts who received prior adjuvant anti-PD1 vs 23% (95% CI 11.8-38.6) in the metastatic setting. Disease control rates (DCR) were comparable in A and B. Six-mo DCR were 11.5% in A, 23.3% in B and 29.5% in C. No unexpected toxicity was observed and recurrent adverse events occurred in 7.7% in A, 11.6% in B and 13.1% in C. Discontinuation due to toxicity was 31% in A, 4.6% in B and 4.9% in C. Table: 1106P

Conclusions

Despite the limitation of a retrospective study, our results suggest that pts with MM respond more frequently to sequential ICI combination when they have previously responded to ICI (SRres), whereas PRes does not impair ORR in pts treated with adjuvant anti-PD1.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Guardamagna: Other, Other, Travel fee to congress: Pierre Fabre, MSD, Novartis, AstraZeneca, BMS. C. Gaudy Marqueste: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Pierre Fabre; Financial Interests, Institutional, Local PI: BMS, MSD, Pfizer, Amgen, GSK, Roche, Novartis, Pierre Fabre, Replimune, Jansen, Kartos, IFX, Huyabio, Regeneron, IO Biotech, Philogen, Sotio, Kinnate, Astra Zenecca, Day One biopharmaceuticals, Sairopa, Catalyst, Sanofi, Immunocore; Other, Other, Travel expenses: BMS, Pierre Fabre, MSD. N. Malissen: Financial Interests, Personal, Advisory Board: Novartis, Janssen-Cilag, AbbVie; Financial Interests, Personal, Invited Speaker: Pierre Fabre Oncologie, L'Oreal, MSD; Financial Interests, Institutional, Local PI: ASTEX. I. Pires da Silva: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche, Novartis; Financial Interests, Personal, Other, Travel Support: BMS, Roche; Financial Interests, Personal, Advisory Board: MSD. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L, IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. J.W. Smithy: Financial Interests, Institutional, Coordinating PI: IO Biotech. M.A. Postow: Financial Interests, Personal, Advisory Board: BMS, Chugai, Merck, Nektar, Pfizer; Financial Interests, Institutional, Coordinating PI: BMS; Financial Interests, Institutional, Local PI: Merck, Novartis. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, Novartis, Merck Serono, Sun Pharma, Sanofi, Sandoz, Immunocore, Boehringer Ingelheim Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant, Advisory Role and Travel support: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role.Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant Role: Pfizer, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role,Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Other, Consultant and Advisory: Erasca; Financial Interests, Personal, Other, Consultant: Philogen; Financial Interests, Personal, Advisory Board: BionTech, Anaveon; 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, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. E.J. Lipson: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Sanofi, Regeneron, Genentech, Eisai, Instil Bio, Natera, Nektar Therapeutics, Pfizer, Rain Therapeutics, CareDx, Immunocore, Novartis, Replimune, HUYA Bioscience International, Sun Pharma, Merck KGaA, Syneos; Financial Interests, Personal, Other, Consultant: OncoSec; Financial Interests, Personal, Stocks/Shares: Iovance; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb, Haystack Oncology; Financial Interests, Institutional, Local PI: Regeneron, Merck, Sanofi. M. Erdmann: Financial Interests, Personal, Advisory Board, Clinical case presentation: Immunocore; Financial Interests, Personal, Invited Speaker, Presentation at workshop for nurses: Novartis; Financial Interests, Personal, Invited Speaker, Presentation at workshop as well as travel/meeting expenses: Pierre Fabre; Financial Interests, Personal, Other, travel expenses: Sanofi. C. Berking: Financial Interests, Personal, Advisory Board: BMS, MSD, InflaRx, Sanofi, Regeneron, Novartis, Pierre Fabre, Delcath, Immunocore; Financial Interests, Personal, Invited Speaker: BMS, Almirall, MSD, Immunocore, Pierre Fabre, Leo Pharma; Financial Interests, Institutional, Coordinating PI: Almirall; Financial Interests, Institutional, Local PI: InflaRx, Immunocore, IOBiotech, Kartos, MSD, Regeneron. C. Robert: Financial Interests, Personal, Advisory Board, Consultancy fees: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, Pfizer, Sun Pharma, Merck, Ultimovacs, Regeneron, EGLE, Philogen, MAAT Pharma; Financial Interests, Personal, Other, Steering Committee: Novartis, Regeneron, Pfizer, IO Biotech; Financial Interests, Personal, Other, IDMC: Ultimovacs; Financial Interests, Personal, Invited Speaker: Pierre Fabre, Sanofi, BMS, MSD, Novartis. All other authors have declared no conflicts of interest.