121MO - Anti-IL-8 (BMS-986253) in combination with nivolumab (NIVO) plus ipilimumab (IPI) in patients (pts) with advanced melanoma: final analysis from the randomized part 2 of the phase 1/2 CA027-002 study

Background

Elevated serum IL-8 is associated with increased tumour burden, immunotherapy resistance, and poor outcomes in many solid tumour types. Low IL-8 correlates with improved response to checkpoint inhibitors. Anti–IL-8 (BMS-986253) is a fully human IgG1κ mAb. Anti–IL-8 +/– NIVO demonstrated tolerability in pts with selected advanced cancers. Here, we report the final analysis from part 2 of CA027-002, a randomized phase 2 study of anti–IL-8 + NIVO + IPI vs placebo (PBO) + NIVO + IPI in pts with advanced melanoma resistant to PD-(L)1 blockade.

Methods

Pts with unresectable, stage III/IV melanoma who had progressed on/after anti–PD-(L)1 agents as their most recent therapy enrolled. No prior anti–cytotoxic T lymphocyte antigen-4 therapy was allowed. Pts were randomized to anti–IL-8 3600 mg IV Q2W + NIVO 1 mg/kg IV Q3W + IPI 3 mg/kg IV Q3W for 4 doses followed by anti–IL-8 3600 mg IV Q2W + NIVO 480 mg IV Q4W (arm A) or PBO + NIVO + IPI followed by PBO + NIVO (arm B). Primary endpoint was ORR by blinded independent central review.

Results

122 pts were randomized to arm A (n=62) or B (n=60). ORR in arm A and B was 15% and 12% (OR 1.3 [95% CI, 0.4–3.6] P=0.68), including complete responses in 5 pts and 1 pt, respectively (Table). Median (95% CI) PFS in arm A and B was 2.1 (1.9–3.8) and 3.3 (1.9–3.7) months (HR 0.94 [95% CI, 0.61–1.45]; P=0.74); 12-month PFS rates were 15% and 12%, respectively. The most common grade ≥3 TRAEs (≥10% in either arm A/B) were diarrhoea (10%/16%), and colitis (6%/12%). TRAEs leading to treatment discontinuation occurred in 14 (23%) and 14 (25%) pts in arm A and B. Table: 121MO

CR, complete response; HR, hazard ratio; OR, odds ratio; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.

Conclusions

In this study population, the addition of anti–IL-8 to NIVO + IPI was well tolerated, but no statistically significant difference for the primary endpoint of ORR or the secondary endpoint of PFS was observed in patients with advanced melanoma who had progressed on/after anti-PD-(L)1 therapy.

Clinical trial identification

NCT03400332.

Editorial acknowledgement

Medical writing and editorial assistance was provided by Keri Wellington, PhD, Benjamin Levine, PhD, and Mel Ward, BA, of Prime, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

M. Simonelli: Financial Interests, Personal, Advisory Board: Incyte, Cytovia, Glaxo; Financial Interests, Personal, Invited Speaker: Glaxo, Bristol Myers Squibb; Financial Interests, Personal, Other, Data Monitoring Committee: Sanofi; Financial Interests, Personal, Other, Steering Committee: BMS/Celgene; Financial Interests, Personal, Other, Travel grant: Roche; Financial Interests, Personal, Other, Travel Grant: Pfizer. M.O. Butler: Financial Interests, Personal, Advisory Board: BMS, Merck, Novartis, Adaptimmune, Iovance, GSK, Sanofi, Roche Possey, Pfizer, Medison, Ideaya, Regeneron; Financial Interests, Personal, Invited Speaker: BMS, Merck, Novartis, Sanofi, Pfizer; Financial Interests, Personal, Advisory Board, Safety Review Committee: Adaptimmune; Financial Interests, Institutional, Other, Conduct Clinical Trial: TCR2, Novartis, Sanofi, Immunocore, GSK, Pfizer, Merck, Bristol Myers Squibb, Regeneron, AstraZeneca, Adaptimmune, IDEAYA Biosciences, Amgen, Instil Bio, Turnstone Biologics, Iovance, Ankara; Financial Interests, Institutional, Research Grant, support clinical trial: Merck; Financial Interests, Institutional, Funding, support clinical trial: Takara Bio; Financial Interests, Institutional, Funding, support quality improvement project: 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, 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: Replimune; 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, Personal, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Personal, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Personal, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Personal, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Personal, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. 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 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.; Financial Interests, Personal, Advisory Board, Consultant Advisor: GI Innovation; Non-Financial Interests, Personal, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Boehringer-Ingelheim, Chugai, Diaccurate, Elevation Oncology, Ellipses Pharmacy, Genmab, Grey Wolf, Incyte, Janssen, MSD, Merus, MonTa, Nanobiotix, Nouscom, Novartis, Servier, SyneosHealth, T-knife, TargImmune, iTeos, Debio; Financial Interests, Personal, Invited Speaker: OncoDNA, PharmaMar, Roche/Genentech; Financial Interests, Personal, Full or part-time Employment, Director, Clinical Research: HM Hospitales Group; Financial Interests, Personal, Full or part-time Employment, Medical Oncologist. Clinical Investigator. Director, Clinical Research: START Madrid - CIOCC (Centro Integral Oncológico Clara Campal); Financial Interests, Personal, Member of Board of Directors, External Independent member of Board of Directors: PharmaMar; Financial Interests, Personal, Ownership Interest: START, Oncoart Associated; Financial Interests, Personal, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi, Merus, Shionogi; Financial Interests, Personal, Steering Committee Member: Novartis; Non-Financial Interests, Personal, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) non-for-profit Foundation; Non-Financial Interests, Personal, Advisory Role: PsiOxus; Non-Financial Interests, Personal, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Personal, Member of Board of Directors, Non-for-profit Foundation, trustee member: Non-for-profit Foundation PharmaMar; Non-Financial Interests, Personal, Advisory Role, Non-for-profit foundation: CRIS Cancer Foundation, non-for-profit ; Non-Financial Interests, Personal, Member: ASCO, ESMO, SEOM, EORTC. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Institutional, Local PI, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer Beigene BioInvent International AB, BMS, Boehringer Ingelheim, Boston, Celgene, Daiichi Sankyo, Debiopharm, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith; Multiple. C. Gebhardt: Financial Interests, Personal, Advisory Board: Almirall, Amgen, Beiersdorf, BioNTech, Bristol Myers Squibb, Immunocore, Janssen, MSD, Novartis, Pierre Fabre, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Sysmex, Sanofi; Financial Interests, Personal, Research Funding: Bristol Myers Squibb, Novartis, Regeneron; Financial Interests, Personal, Other, Co-founder: Ermagnostix and Dermagnostix R&D. 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; Financial Interests, Personal, Steering Committee Member: Novartis; Financial Interests, Institutional, Research Grant: Pierre Fabre. A.M. Haydon: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis. G. Quereux: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squib, Novartis, Pierre Fabre Dermatologie. J. Walker, M. Kumar: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Chakraborty, X. Zhu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. I. Melero: Financial Interests, Personal, Advisory Board: Agneus, Alligator Bioscience, AstraZeneca, BMS, BioLineRx, Boehringer Ingelheim, Boston Pharma, CRISPR Therapeutics, CatalYm GmbH, Crescendo Biologics, Curon BIopharmaceutical, EMD Serono, F-Star, Genentech, Genmab, Highlight Therapeutics, Hookipa Pharma, HotSpot Therapeutics, Inc., ImmuneSensor Therapeutics, Inc., Janssen, MSD, Merus N.V., Monopteros Therapeutics, NOXXON Pharma AG, Numab, Phenomic Bio, Pieris Pharmaceuticals GmbH, Pierre Fabre, Roche, Sanofi, Senti Biosciences, Servier, Shattuck Labs, Third Rock Ventures; Financial Interests, Personal, Other, Consultant: Pharma Mar, Pioneering Medicines; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, BMS, Genmab, Alligator.