520MO - Safety and efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with recurrent/metastatic cervical cancer (R/M Cx Ca) in checkmate 358

Background

Anti–PD–1–based treatment (tx) is approved in 1st (1L)– and 2nd (2L)–line settings for programmed death ligand 1 (PD–L1)+ R/M Cx Ca; however, objective response rate (ORR) with single–agent tx is <15% (Chung et al SGO 2021 abstract). Here, we report safety and efficacy of NIVO ± IPI in pts with R/M Cx Ca in CheckMate 358 (NCT02488759), a phase 1/2 study of NIVO and NIVO–based combinations in virus–associated solid tumors.

Methods

Adults with R/M squamous Cx Ca and ≤2 prior systemic therapies received NIVO 240 mg Q2W, NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W (N3I1), or NIVO 1 mg/kg + IPI 3 mg/kg Q3W for 4 cycles followed by NIVO 240 mg Q2W (N1I3), for ≤24 mo or until disease progression, unacceptable toxicity or consent withdrawal. N3I1 vs N1I3 was initially randomized (rand); promising signal led to an expansion cohort with N1I3 (exp). Investigator–assessed ORR was the primary endpoint; overall survival (OS), progression free survival (PFS) and duration of response (DOR) were secondary endpoints; safety and select tissue and blood biomarkers were exploratory endpoints. Cross–cohort comparison was not planned.

Results

Among 176 pts treated, (NIVO n = 19; N3I1 n = 45; pooled N1I3 n = 112 [rand n = 45; exp n = 67]), median follow–up was 30.4 mo. Responses (table) were observed regardless of tumor PD-L1 status. Median DOR (mo; 95% CI) was not reached [NR] (35.3–NR), 24.4 (8.7–NR) and 34.1 (11.5–NR), respectively. Median OS was 21.6 (8.3–46.9), 15.2 (9.0–36.2) and 20.9 (14.4–32.8); median PFS was 5.1 (1.9–9.1), 3.8 (2.1–10.3) and 5.8 (3.8–9.3). The incidence of individual grade 3/4 IMAEs was <6% (NIVO), <7% (N3I1), and <6% except for hepatitis (16%) (pooled N1I3) with no new safety signals. There was one tx–related death (colitis) in the exp N1I3 arm. Table: 520MO

Efficacy of NIVO±IPI in R/M Cx Ca

*By tumor proportion score (TPS).

Conclusions

Chemotherapy-free dual immunotherapy NIVO + IPI regimens can provide durable tumor regression with significant but manageable toxicity in R/M Cx Ca regardless of PD–L1 status and warrant further investigation.

Clinical trial identification

NCT02488759.

Editorial acknowledgement

Writing and editorial assistance was provided by Thai Cao, MS, and Meenakshi Subramanian, PhD, 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 and Ono Pharmaceutical Company Ltd. (Osaka, Japan).

Disclosure

A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, ImmunoGen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. K.N. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Eisai, Emd Serono, Gsk/Tesaro, Genentech/Roche, Hengrui, Immunogen, Imab, Mereo, Myriad, Caris, Mersana, Novartis, Novocure, Oncxerna, OncoNova, tarveda, VBL Therapeutics; Financial Interests, Personal, Full or part-time Employment: GOG Partners Associate Director; Financial Interests, Institutional, Full or part-time Employment: NRG Ovarian Cancer Chair; Financial Interests, Personal, Royalties: UP to Date; Financial Interests, Institutional, Invited Speaker, international CO-PI, local site PI: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Immunogen, GSK/Tesaro, Lilly, PTC Therapeutics, Daiichi Sankyo, Regeneron, Artios, Bolt, Verastem; Non-Financial Interests, Invited Speaker: GOG. T. Meyer: Financial Interests, Personal, Advisory Board: Ipsen, AstraZeneca, Eisai, Bayer, Roche, Adaptimmune, Boston Scientific; Financial Interests, Institutional, Research Grant: Bayer, BTG. L. Devriese: Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Merck. A. Amin: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb. C.D. Lao: Financial Interests, Institutional, Invited Speaker, Research funding: BMS, Novartis, Genentech, Oncosec. V. Boni: Financial Interests, Personal, Full or part-time Employment: NEXT Madrid, Universitary Hospital Quironsalud Madrid; Financial Interests, Personal, Advisory Role: Puma Biotechnology, Ideaya Biosciences, Loxo Therapeutics, CytomX Therapeutics, Guidepoint, Oncoart; Financial Interests, Personal, Invited Speaker: Eli Lilly, MSD; Financial Interests, Personal, Other, Travel/Accomodations: Bayer; Financial Interests, Institutional, Research Grant: Abbvie, ACEO, Adaptaimmune, Amcure, AMGEN, Amunix, AstraZeneca, Bristol Myers Squibb Cytomx, GSK, Genentech/Roche, H3, Incyte, Janssen, Kura, Lilly, Nektar, Menarini, Merck, Merus, Nanobiotix, Novartis, Pfizer, PharmaMar, Principia, PUMA, Sanofi, Taiho, Tesaro, BeiGene, Transgene, Innovio, MSD, PsiOxus, Seattle Genetics, Mersana, Daiichi, Nektar, Astellas, ORCA, Boston Therapeutics, Dynavax, DebioPharm, Boehringer Ingelheim, Regeneron, Millennium, Synthon, Spectrum, Rigontec, Zenith. W.H. Sharfman: Financial Interests, Personal, Invited Speaker, non-branded speaker series consultant and speaker: BMS; Financial Interests, Personal, Other, Leads discussion groups on melanoma therapy: Merck; Financial Interests, Personal, Advisory Board: Regeneron, Pfizer, AmerisourceBergen; Financial Interests, Institutional, Invited Speaker: BMS, Merck, Genentech, AstraZeneca, Novartis. M. Tahara: Financial Interests, Personal, Advisory Board: Merck Biopharma, Ono pharma, Bristol- Myers Squibb, MSD, Pfizer, Bayer, Lilly, Rakuten Medical, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, Ono Pharma, Novartis, Pfizer, Bristol-Myers Squibb, Loxo, GlaxoSmithKline, Lilly, Rakuten Medical; Financial Interests, Institutional, Research Grant: Bayer. S.L. Topalian: Financial Interests, Personal, Advisory Role: AstraZeneca, Dragonfly Therapeutics, Five Prime Therapeutics, Immunocore; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Dragonfly Therapeutics, Five Prime Therapeutics. M.E. Magallanes Maciel: Financial Interests, Institutional, Leadership Role: Centro Oncologico Internacional. A. Molina Alavez: Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly, AstraZeneca, Amgen; Financial Interests, Personal and Institutional, Principal Investigator: Bayer, Bristol Myers Squibb, Janssen, MSD, Eli Lilly, AstraZeneca, Amgen; Financial Interests, Personal, Speaker’s Bureau: Glaxo; Financial Interests, Institutional, Other: Roche. A. Khan: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb. C. Copigneaux: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M. Lee: Financial Interests, Personal, Other, Consultant: Bristol Myers Squibb. C. Garnett-Benson: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. X. Wang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. R.W. Naumann: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Clovis, OncoMed, Eisai, Bristol Myers Squibb, Agenus, SutroBio, GOG Partners, GSK; Other, Institutional, Principal Investigator: OncXerna, SutroBio, Bristol Myers Squibb, Mersana; Financial Interests, Personal, Speaker’s Bureau: Seagen; Non-Financial Interests, Personal, Leadership Role: GOG Partners; Other, Institutional, Research Grant: GOG Partners; Non-Financial Interests, Personal, Other, Steering Committee: OncXerna; Financial Interests, Personal, Other, DSMB Member: Genelux. All other authors have declared no conflicts of interest.