LBA20 - A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC)

Background

High-risk, early-stage ER+ HER2− BC treatment includes NACT and adjuvant ET. CheckMate 7FL (CM-7FL; NCT04109066) is the first prospective, phase 3, randomized trial investigating NIVO + NACT + adjuvant ET in this clinical setting.

Methods

This study enrolled newly diagnosed ER+ HER2− BC pts, stages T1c–2 and N1–2 or T3–4 and N0–2, of grade 2 (ER 1–‍10%) or 3 (ER ≥ 1%). Pts were randomized 1:1 to NACT + NIVO 360 mg Q3W/NIVO 240 mg Q2W (arm A) or NACT + PBO (arm B). In April 2022, based on external data, the trial was closed to new enrollment; the primary endpoint was amended to only pathological complete response (pCR; ypT0/is ypN0) rate in the modified ITT population (mITTP; database lock 14 Apr 2023). Secondary endpoints included pCR rates in programmed death ligand 1 (PD-L1)-positive (PD-L1+) pts (SP142 ≥ 1%), residual cancer burden (RCB) 0–1 rates (all pts and PD-L1+), adverse event (AE) incidences, and death incidences.

Results

830 pts were screened, 521 randomized (arm A/B, n = 263/258), and 510 were included in the mITTP. Baseline characteristics were balanced across arms. pCR rate was overall significantly higher in arm A (24.5%) vs B (13.8%; P = 0.0021) and in the stage III subgroup (Arm A/B, 30.7%/8.1%). The benefit of NIVO on pCR was higher in PD-L1+ pts (adjusted difference [AD], 24.1%; 44.3% in arm A, 20.2% in arm B). RCB 0–1 rates improved overall and more so in PD-L1+ pts. In the NACT phase, grade 3/4 treatment-related AEs incidence was similar across arms (arm A/B, n = 92[35%]/82[32%]). Two deaths (pneumonitis, hepatitis) in arm A were study-drug related. Immune-mediated AE (IMAE) incidence was higher in arm A vs B. Table: LBA20

CheckMate 7FL key efficacy results, mITTP

Conclusions

CM-7FL met its primary endpoint with significantly improved pCR and RCB 0–1 rates (enhanced in PD-L1+ pts) with NIVO + NACT, with increased IMAE incidence and an overall safety profile consistent with that of NIVO and CT.

Clinical trial identification

NCT04109066.

Editorial acknowledgement

Medical writing and editorial support were provided by Sandra Page, PhD, and Agata Shodeke, PhD, of Spark Medica Inc., funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

S. Loi: Financial Interests, Institutional, Advisory Board, Consultant: Aduro Biotech, Novartis, GSK, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics, Pfizer, Seattle Genetics; Financial Interests, Institutional, Advisory Board, COnsultant: PUMA Biotechnologies, BMS; Financial Interests, Institutional, Advisory Board, consultant: Gilead Therapeutics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, PUMA Biotechnology, Seattle Genetics, Roche - Genentech, Eli Lilly, Nektar Therapeutics, AstraZeneca; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech; Non-Financial Interests, Advisory Role, consultant (not compensated): Gilead Therapeutics, Eli Lilly, Pfizer. G. Curigliano: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Celcuity, Daiichi Sankyo, Exact Sciences, Gilead, Eli Lilly, Menarini, Merck, Pfizer, Roche, Veracyte, Ellipsis; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Institutional, Funding, Phase I studies: Astellas, AstraZeneca, Blueprint Medicine, Daiichi Sankyo, Kymab, Novartis, Philogen, Roche, Sanofi, BMS; Financial Interests, Institutional, Research Grant, Investigator initiated trial: Merck; Financial Interests, Institutional, Funding, Phase I clinical basted: Relay Therapeutics; Non-Financial Interests, Personal, Officer, Advisor for Ministry of Health: Consiglio Superiore di SanitàOfficer, Italian National Health Council ; Non-Financial Interests, Personal, Officer, ESMO Clinical Practice Guidelines Chair: ESMO; Non-Financial Interests, Personal, Member of Board of Directors, Chair of Clinical Practice Guidelines Committee: ESMO; Non-Financial Interests, Personal, Advisory Role, Member of the Advisory Counci: Europa Donna, EUSOMA; Non-Financial Interests, Personal, Member of Board of Directors, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Personal, Advisory Board, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori. R.F. Salgado: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Daiichi Sankyo, Exact Sciences; Non-Financial Interests, Personal, Other, Travel and congress registration support: AstraZeneca, BMS, Merck, Roche; Financial Interests, Personal, Other, Lectures: AstraZeneca, Daiichi Sankyo, Exact Sciences; Financial Interests, Institutional, Research Grant: BMS, Merck, Puma, Roche; Non-Financial Interests, Personal, Advisory Role: Case 45; Financial Interests, Personal, Other, Travel and congress registration support: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Owkin. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Sanofi, Gilead; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Lilly, AstraZeneca, MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker, ESMO symposium: Gilead; Financial Interests, Institutional, Advisory Board, scientific board: Elsan; Financial Interests, Institutional, Steering Committee Member: Roche Genentech, BMS, AstraZeneca, Sanofi; Financial Interests, Institutional, Coordinating PI, clinical research funding to my institution: Taiho; Non-Financial Interests, Member of Board of Directors, Société Française de Sénologie et Pathologie Mammaire: SFSPM; Non-Financial Interests, Principal Investigator, H2020 funding: European Commission. C. Rojas: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Knight, MSD, Pfizer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Pfizer, Roche, Roche, Sanofi; Financial Interests, Personal, Member of Board of Directors: Bradford Hill. M. Kok: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Roche, AstraZeneca/Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Roche, MSD, AstraZeneca/Daiichi Sankyo; Financial Interests, Institutional, Speaker’s Bureau: Bristol Myers Squibb, Gilead; Financial Interests, Institutional, Product Samples: Natera. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Piere Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, SeaGen, Zymeworks, Genentech, Innoup, Millenium, Pharmalex Spain SLU; Financial Interests, Personal, Other, SC: Byondis B.V., Glaxo, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La RocheLtd, Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Coordinating PI: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuelligpharma, Viatris; Financial Interests, Personal, Other, IDMC: Roche; Financial Interests, Personal, Advisory Board: Sandoz-Hexal, Seagen, Aptitude Health, Pfizer, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Funding: AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Palleos, Seagen, TRIO, WSG; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Founding Editor: BreastCare Journal. E.A. Mittendorf: Financial Interests, Personal, Advisory Board: AstraZeneca, BioNTech, Merck; Non-Financial Interests, Personal, Steering Committee Member: Bristol Myers Squibb, Roche/Genentech; Financial Interests, Institutional, Research Funding: Gilead; Financial Interests, Institutional, Research Grant, SU2C grant: Roche/Genentech; Financial Interests, Personal, Research Funding: Susan Komen for the Cure; Financial Interests, Personal, Speaker, Consultant, Advisor: Susan Komen for the Cure; Non-Financial Interests, Personal, Member of Board of Directors: ASCO. D. Yardley: Financial Interests, Institutional, Research Funding: AbbVie, Ambrx, Amgen, AstraZeneca, BIOMARIN, Biothera Pharmaceuticals, Clovis Pharma, Dana Farber, Cancer Institute, Eisai, Lilly, Roche/Genentech, G1 Therapeutics, Gilead Sciences, Incyte, Innocrin Pharmaceuticals, MacroGenics, MedImmune, Medivation, Merck, Merrimack Pharmaceuticals, Nektar Therapeutics, Novartis, NSABP, Odonate Therapeutics, Pfizer, Polyphor, Stemline Therapeutics, US Oncology, UT Southwestern; Financial Interests, Institutional, Advisory Role: AstraZeneca, Gilead Sciences, Immunomedics, Integra Connect, Novartis, Sanofi-Aventis, Stemline Therapeutics. L. Pusztai: Financial Interests, Personal, Advisory Board, advisory board, trial steering committee membership: AstraZeneca; Financial Interests, Personal, Advisory Board: pfizer, roche genentech, novartis, Exact Sciences, Natera; Financial Interests, Personal, Advisory Board, advisory board, trial steering committee: Merck; Financial Interests, Personal, Advisory Board, advisory board: Biotheranostics; Financial Interests, Personal, Advisory Board, investigator meeting: Biovica; Financial Interests, Institutional, Trial Chair, clinical trial support to institution: pfizer, merck; Financial Interests, Institutional, Local PI, clinical trial support to institution: Seagen, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant: Bristol Myers Squibb; Non-Financial Interests, Advisory Role, member of the scientific advisory board: Breast Cancer Research Foundation; Non-Financial Interests, Member of Board of Directors: SWOG Hope Foundation; Non-Financial Interests, Institutional, Product Samples, material transfer agreement: Pfizer. A. Suarez Zaizar: Non-Financial Interests, Institutional, Principal Investigator: CENEIT Oncologicos. F. Ades: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. R. Chandra: Financial Interests, Personal, Full or part-time Employment, BMS employee; Clinical Scientist for 7FL: Bristol Myers Squibb. R. Nathani: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J.Q. Wu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. H.L. McArthur: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Daiichi Sankyo, Crown Bioscience, Gilead, Seattle Genetics, Puma Biotechnology, Bristol Myers Squibb, Lilly, Immunomedics, Roche, Novartis; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Institutional, Funding, Funding to institution: Merck, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Steering Committee Member: AstraZeneca. All other authors have declared no conflicts of interest.