92MO - Neoadjuvant nivolumab (NIVO) + palbociclib (PALBO) + anastrozole (ANA) for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2_) primary breast cancer (BC): CheckMate 7A8

Background

Cyclin-dependent kinase (CDK) 4/6 inhibition + ER signaling blockade is a highly effective treatment option for metastatic ER+/HER2− BC. Preclinical studies show evidence of CDK 4/6 and programmed death-1 (PD-1) blockade synergy. CheckMate 7A8, a non-comparative, phase 2 study, evaluated neoadjuvant NIVO + PALBO + ANA in patients (pts) with ER+/HER2− primary BC. Here, we report safety outcomes from the safety run-in phase.

Methods

Eligible pts were men or postmenopausal women with newly diagnosed, histologically confirmed, untreated ER+/HER2− BC with primary tumor ≥ 2 cm, an ECOG performance status of 0/1, and eligible for post-treatment surgery. Pts received NIVO 480 mg IV every 4 wks (1 cycle), PALBO 125 mg (dose level [DL] 1) or 100 mg (DL 2) PO once daily (QD) for 3 wks per cycle, and ANA 1 mg PO QD, for 5 cycles total/until disease progression. Primary endpoint (safety run-in phase) was the number of pts with occurrence of dose-limiting toxicity (treatment-emergent adverse events [AEs] within 4 wks of treatment start).

Results

As of safety data review on 6 May 2021, 21 pts (DL 1: n = 9; DL 2: n = 12) were treated. Most common grade ≥3 treatment-related AEs (TRAEs) were elevated alanine or aspartate aminotransferase, neutropenia, and decreased white blood cell count in DL 1 (n = 2 each; 22.2%), and decreased neutrophil count (n = 5; 41.7%) in DL 2. 5 pts (DL 1) and 4 pts (DL 2) discontinued treatment due to toxicity, mainly grade ≥3 hepatic TRAEs (Table). The study was closed on 27 July 2021 after safety run-in ended. Additional safety and preliminary efficacy data (database lock: 3 February 2022) will be presented. Table: 92MO

Conclusions

Neoadjuvant NIVO + PALBO + ANA showed a higher incidence of grade ≥3 hepatic TRAEs than historical single-agent safety profiles. These findings show a potential safety risk for the use of endocrine therapy with PD-1 + CDK 4/6 blockade.

Clinical trial identification

NCT04075604.

Editorial acknowledgement

Writing and editorial assistance was provided by Vidya Rajagopalan of Evidence Scientific Solutions, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb, Princeton, NJ, USA.

Funding

Bristol Myers Squibb, Princeton, NJ, USA.

Disclosure

G. Jerusalem: Financial Interests, Institutional, Research Grant: Novartis, Pfizer; Financial Interests, Institutional, Royalties: Roche; Financial Interests, Personal, Other, Consulting Fees: Novartis, Amgen, Roche, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Daiichi Sankyo, AbbVie; Financial Interests, Personal, Invited Speaker, Honoraria: Novartis, Roche, Amgen, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Seagen; Financial Interests, Personal, Other, Travel/Accommodations/Expenses/Accommodations: Novartis, Roche, Pfizer, Lilly, Amgen; Financial Interests, Personal, Other, Travel/Accommodations/Expense: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis, Roche, Amgen, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Daiichi Sankyo, AbbVie; Financial Interests, Personal, Other, Medical Writing: Novartis, Roche, Lilly, Amgen, Bristol Myers Squibb, AstraZeneca, MedImmune, Merck. A. Prat: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Roche, Amgen, Bristol Myers Squibb, Boehringer, Puma, Oncolytics Biotech, Daiichi Sankyo, AbbVie, AstraZeneca, NanoString Technologies; Financial Interests, Institutional, Sponsor/Funding, Research Funding: Novartis, Roche, Incyte, Puma Biotech; Financial Interests, Personal, Invited Speaker, Honoraria: Roche; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Lilly, Daiichi Sankyo, Amgen, Guardant Health; Financial Interests, Personal, Other, Travel/Accommodations/Expense: Daiichi Sankyo. R.F. Salgado: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb; Non-Financial Interests, Personal, Other, Travel/Accommodations: Roche, Puma, Merck. M. Reinisch: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Daiichi Sankyo, Roche, Seagen, Somatex, MSD, Lilly, Pfizer; Financial Interests, Personal, Member, Honoraria: Novartis; Financial Interests, Personal, Advisory Board, Consultancy: Somatex; Financial Interests, Personal, Other, Travel: Pfizer, Novartis. C. Saura: Financial Interests, Personal, Advisory Board: AstraZeneca, AX'Consulting, Byondis B.V., Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann, ISSECAM, Medical Statistics Consulting, MediTech, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, Seagen, Zymeworks; Non-Financial Interests, Institutional, Research Grant: Aragon Pharmaceuticals, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb, Byondis B.V., Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, German Breast Group Forchungs, GlaxoSmithkline, Immunomedics, Innoup Farma, International Breast Cancer Study Group (IBCSG), Macrogenics, Medica Scientia Innovation Research, Menarini Ricerche, Merck, Merus, Millennium Pharmaceuticals, Novartis, Pfizer, Piqur Therapeutics, Puma, Roche, Sanofi-Aventis, Seattle Genetics, Synthon, Zenith Pharma; Non-Financial Interests, Personal, Member: American Association for Cancer Research (AACR), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), SOLTI group (Academic research group in breast cancer), Spanish Society of Medical Oncology (SEOM). J. Filian, F. Ades, A. Mazzei-Abba: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. N. Huang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.M. Tolaney: Financial Interests, Personal and Institutional, Other, Ad Board Participant/Consultant; Research Funding (to institution): Bristol Myers Squibb, AstraZeneca, Eli Lilly, Merck, Novartis, Seagen, Sanofi, Eisai, Gilead, Pfizer, Genentech/Roche, Odonate; Financial Interests, Institutional, Research Grant: Nektar, NanoString, Exelixis, Cyclacel; Financial Interests, Personal, Advisory Board: Certara, Mersana Therapeutics, G1 Therapeutics, OncoSec, OncoPep, CytomX, Athenex, Ellipses Pharma, 4D Pharma, Puma, Zymeworks, Zentalis, Reveal Genomics, OncXerna, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Other, Consultant: Blueprint Medicines. All other authors have declared no conflicts of interest.