200MO - Anti-IL-8 BMS-986253 + nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with advanced cancer: update of initial phase 1 results

Background

IL-8 is a CXC chemokine that exerts protumorigenic effects by promoting immunosuppression through neutrophil and myeloid-derived suppressor cell recruitment into the tumor microenvironment. Elevated serum IL-8 (sIL-8) is a negative prognostic factor in multiple cancer types. BMS-986253, a fully human IgG1κ anti–IL-8 mAb, binds IL-8 and prevents signaling through CXCR1/CXCR2. We present updated results from part 1 of the phase 1/2 trial of BMS-986253 + NIVO ± IPI in pts with advanced cancer (NCT03400332).

Methods

Pts with metastatic solid tumors and sIL-8 > 10 pg/mL at screening received IV BMS-986253 Q2W (1200, 2400, or 3600 mg) or Q4W (600, 1200, or 2400 mg) + NIVO 480 mg Q4W; pts with any sIL-8 at screening received BMS-986253 3600 mg Q2W + 4 doses of NIVO 1 mg/kg + IPI 3 mg/kg Q3W followed by BMS-986253 3600 mg Q2W + NIVO 480 mg Q4W.

Results

As of August 4, 2022, 159 pts (median age, 63 yr [range, 32–87]) received BMS-986253 with NIVO (n = 144) or BMS-986253 with NIVO + IPI (n = 15). Both regimens were well tolerated. Any-grade/grade ≥ 3 TRAEs were reported in 46.5%/7.6% of pts treated with BMS-986253 + NIVO and in 66.7%/33.3% of pts treated with BMS-986253 + NIVO + IPI. BMS-986253 exposure increased dose-proportionally. BMS-986253 resulted in dose-dependent reductions in free sIL-8, with tumor IL-8 suppression detected in most pts evaluated. Partial responses were observed in 6 of 46 (13%) pts with melanoma treated with BMS-986253 + NIVO; all pts with a response were previously treated with anti–PD-1 therapy, and 5 were previously treated with anti–CTLA-4 therapy. Complete response was achieved in 1 of 6 pts with melanoma treated with BMS-986253 + NIVO + IPI. Clinical activity with BMS-986253 + NIVO ± IPI was observed in pts with other tumor types.

Conclusions

BMS-986253 in combination with NIVO ± IPI demonstrated a tolerable safety profile with dose-proportional pharmacokinetics and robust free sIL-8 suppression. Preliminary and durable antitumor activity was observed across a range of doses/regimens. These findings support further evaluation of BMS-986253 in pts with melanoma following anti–PD-(L)1 therapy in the phase 2 part of this study.

Clinical trial identification

NCT03400332.

Editorial acknowledgement

Editorial assistance was provided by Matthew Weddig of Spark Medica Inc (USA), funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

E. Calvo: Financial Interests, Personal, Advisory Board: Adcendo, Amunix, Anaveon, AstraZeneca, BMS, Chugai, Elevation Oncology, Ellipses Pharmacy, Genmab, Janssen, MonTa, MSD, Nanobiotix, Nouscom, Novartis, Servier, SyneosHealth, T-knife, TargImmune; 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, Member of the Board of Directors, External Independent member of Board of Directors: PharmaMar; 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, Ownership Interest: Oncoart Associated, START; Financial Interests, Personal, Member, Steering Committee Member, Member of Data Monitoring Committee: BeiGene, Sanofi; Financial Interests, Personal, Member, Steering Committee Member: Novartis; Non-Financial Interests, Personal, Other, Chair of the Independent Data Monitoring Committee: EORTC IDMC; Non-Financial Interests, Personal, Other, Non-for-profit Foundation. President and co-founder: INTHEOS (Investigational Therapeutics in Oncological Sciences) Foundation; Non-Financial Interests, Personal, Advisory Role: PsiOxus; Non-Financial Interests, Personal, Member: ASCO, EORTC, ESMO, SEOM. D. Davar: Financial Interests, Institutional, Research Grant: Arcus, Checkmate Pharmaceuticals, CellSight Technologies, Immunocore, Merck, Tesaro/GSK; Financial Interests, Personal, Other, Consultant: Checkmate Pharmaceuticals, Clinical Care Options (CCO), Finch Therapeutics, Gerson Lehrman Group (GLG), Medical Learning Group (MLG), Xilio Therapeutics; Financial Interests, Personal, Speaker’s Bureau: Castle Biosciences; Financial Interests, Personal, Other, Intellectual Property: US Patent 63/124,231, “Compositions and Methods for Treating Cancer”, Dec 11, 2020, US Patent 63/208,719, “Compositions and Methods For Determining Responsiveness to Immune Checkpoint Inhibitors (ICI), Increasing Effectiveness of ICI and Treating Cancer”, June 9, 2021. M. Gutierrez: Financial Interests, Personal, Invited Speaker: Guardant Health; Financial Interests, Personal, Stocks/Shares: COTA Healthcare; Financial Interests, Institutional, Invited Speaker: Merck, BMS, Incyte, NexCure, Pfizer, Roche/Genentech, Boehringer Ingelheim, GSB Pharma, Moderna, Eisai, Silenseed, Seattle Genetics, Regeneron, Sanofi, Johnson & Johnson, MedImmune, Checkpoint Therapeutics, Acerta Pharmaceuticals, Arcus Biosciences, Array BioPharma, Bayer, Celgene, Compass Therapeutics, Constellation Pharmaceuticals, Cyter, EMD Sereno, Fate Therapeutics, GlaxoSmithKline, Infinity, Pharmacyclics, Synlogic, Tesaro, Vedanta. V. Moreno Garcia: Financial Interests, Personal, Other, Consulting fees: Roche, BMS, Janssen, Basilea, Bayer; Financial Interests, Institutional, Principal Investigator, Institutional Funding: AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BioInvent International AB, BMS, Boehringer, 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, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith. T. Marron: Financial Interests, Institutional, Research Grant: BMS, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: Regeneron; Financial Interests, Personal and Institutional, Advisory Board: Regeneron. D.J. Renouf: Financial Interests, Personal and Institutional, Other, Travel funds and research funding: Roche; Financial Interests, Personal, Advisory Board: Bayer, Elevation. M. Joerger: Financial Interests, Institutional, Advisory Role: Novartis, AstraZeneca, Basilea Pharmaceutica, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi; Financial Interests, Personal, Research Grant: Swiss Cancer Research; Financial Interests, Personal, Other, Travel grants: Roche, Sanofi, Takeda. S. Barriga Falcon: Financial Interests, Institutional, Full or part-time Employment: BMS; Financial Interests, Institutional, Stocks/Shares: BMS. J. Fan: Financial Interests, Personal, Full or part-time Employment: BMS. E. Gibson: Financial Interests, Personal and Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Stocks/Shares: Bristol Myers Squibb. D. Chakraborty: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. V. Arora: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. I. Melero: Financial Interests, Personal, Other, Grants and personal fees pertaining to the conduct of the study: Bristol Myers Squibb; Financial Interests, Personal, Other, Grants and personal fees: Genmab, Roche, AstraZeneca, PharmaMar; Financial Interests, Personal, Other, Personal consulting fees: F-Star, Numab, Gossamer, Pieris, Hotspot, Biolinerx, Bioncotech, Dompe, Boston Therapeutics, Alligator. All other authors have declared no conflicts of interest.