854O - INTERLINK-1: Phase III study of cetuximab (CTX) ± monalizumab (M) in participants (pts) with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) with disease progression on/after platinum chemotherapy (CT) and previously treated with an immune checkpoint inhibitor (ICI)

Background

First-line (1L) treatment for R/M HNSCC includes ICI +/- CT or CT + CTX. Treatment after 1L failure is not clearly defined. Preliminary data suggest M (anti-NKG2A) + CTX may have clinically useful antitumour activity in R/M HNSCC.

Methods

In INTERLINK-1 (NCT04590963), pts with incurable R/M HNSCC (oral cavity/oropharynx/hypopharynx/larynx) were randomised 2:1 to M (750 mg IV Q2W) or placebo (P) + CTX (400 mg/m² IV then 250 mg/m² IV Q1W). Primary endpoint was overall survival (OS) in pts with human papillomavirus unrelated (uHPV) cancer (any non-oropharyngeal cancer [OPC] and HPV negative OPC). Secondary endpoints included OS in the full analysis set (FAS; includes uHPV and HPV positive OPC); progression-free survival (PFS) and objective response rate (ORR) in the uHPV set and FAS; and safety in all pts who received study treatment (safety analysis set [SAS]). Futility was assessed at interim analysis 1 (IA1) with 25% information fraction.

Results

At data cut-off (IA1 11 May 2022), 175 and 89 pts in the FAS (N=264) and 145 and 71 pts in the uHPV set (N=216) were randomised (on/before 11 March 2022) to M + CTX and P + CTX, respectively. OS hazard ratio (HR) for M + CTX vs P + CTX in the uHPV set was 1.00 (95% confidence interval [CI], 0.66–1.54; p=0.989) and in the FAS was 1.03 (95% CI, 0.70–1.53; p=0.891; Table). PFS HR was 1.11 (95% CI, 0.79–1.57) in the uHPV set and 1.11 (95% CI, 0.82–1.51) in the FAS. ORR was numerically higher with P + CTX vs M + CTX; duration of response (DoR) was similar between arms. M + CTX was tolerable. Table: 854O

AE, adverse event; IQR, interquartile range; m, median; mo, months; NR, not reached; OR, odds ratio.

Conclusions

In this incurable pt population previously treated with CT and ICI, M + CTX did not improve OS compared with P + CTX. The safety profile was acceptable. ORR with P + CTX was higher than previous reports.

Clinical trial identification

NCT04590963.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Elaine Groat, PhD, of CMC Connect, a division of IPG Health Medical Communications, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca, bms, msd, innate pharma, merck serono, Roche; Financial Interests, Institutional, Other, research funding: Seagens; Non-Financial Interests, Principal Investigator: AstraZeneca. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Merck–Serono, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics e GSK.; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck–Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Buran.. K.J. Harrington: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Merck, MSD, Pfizer, Replimune, Oncolys, Vyriad, Idera; Financial Interests, Institutional, Other, Honoraria for lectures: Amgen, AstraZeneca, BMS, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board, Advisory board for CD47 assets: Arch Oncology; Financial Interests, Institutional, Advisory Board, Development of DDR assets: ARTIOS; Financial Interests, Institutional, Advisory Board, Development of exosomal STING agonist: Codiak; Financial Interests, Institutional, Advisory Board, Development of oncolytic adenovirus: PsiVac; Financial Interests, Institutional, Funding, Research: AstraZeneca, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Funding, Development of oncolytic HSV platform.: Replimune; Non-Financial Interests, Leadership Role, Chair of Steering Committee: ART NET; Non-Financial Interests, Other, Member of Global Steering Committee: MR - Linac. R. Haddad: Financial Interests, Personal, Advisory Board: bms, Merck, EMD serono, Boehringer ingelheim, eisai, bayer, merus, AstraZeneca, Genentech, pfizer, genmab, exelexis, coherus,; Financial Interests, Personal, Other, Data Safety Monitoring Board (DSMB): nanobiotix, psi, Hookipa; Financial Interests, Personal, Royalties: up to date; Financial Interests, Institutional, Invited Speaker, Grant To Hospital For Clinical Trials: Merck BMS, EMD, AstraZeneca, Incyte, Kura; Non-Financial Interests, Other, panel chair guidelines: nccn. L.L. Siu: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Roche, Seattle Genetics, Voronoi, Arvinas, Tessa, Navire, Relay Therapeutics, Amgen, Marengo, InterRNA, Medicenna, Hoopika, Coherus, Tubulis, LTZ Therapeutics; Financial Interests, Personal, Other, Spouse is co-founder: Treadwell Therapeutics; Financial Interests, Personal, Stocks/Shares, Spouse has stock ownership: Agios; Financial Interests, Institutional, Invited Speaker: Novartis, Bristol Myers Squibb, Pfizer, Boerhinger-Ingelheim, Merck, GSK, Roche/Genentech, AstraZeneca, Astellas, Bayer, Amgen, Symphogen, Intensity Therapeutics, Shattucks, EMD Serono; Non-Financial Interests, Advisory Role: ICR, Dana Farber Harvard Cancer Center. 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, GSK, Lilly, Rakuten Medical, Bayer; Financial Interests, Institutional, Research Grant: Bayer. J. Machiels: Financial Interests, Institutional, Advisory Board: novartis, MSD, Pfizer, Roche, Debio, AstraZeneca, Innate, Nanobiotix, Bayer, Merck-Serono, Boerhinger-Ingelheim, BMS, Pfizer, Cue Pharma, Incyte, Janssen, Johnson & Johnson, ALX Oncology, F-star, nektar, F-star, Seagen, astellas, genmab; Financial Interests, Institutional, Other, Travel expense: Gilead, MSD, sanofi; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, MSD, iTeos, eTheRNA, Pfizer, Ceylad, MSD, Novartis, KURA, Roche, Lilly, Boehringer, Sanofi-Aventis, Incyte, Bayer, Merck - Serono, Janssen, Johnson & Johnson, Amgen, AbbVie, GalxoSmithKline; Non-Financial Interests, Leadership Role, Chair: EORTC head and neck group. D. Rischin: Financial Interests, Institutional, Research Grant: MSD, Bristol Myers, Roche, Regeneron, ALX Oncology, GSK, Decibel Therapeutics; Non-Financial Interests, Personal, Other, Advisory Boards – all uncompensated. Participation on a Data Safety Monitoring Board or Advisory Board: MSD, Regeneron, Sanofi. R. Ferris: Financial Interests, Personal, Advisory Board: AbbVie, Bristol Myers Squibb, Coherus BioSciences Inc, DermTech, EMD Serono, Eli Lily, Genmab, Hookipa Biotech GmbH, Instil Bio, Inc., Janssen, Lifescience Dynamics, MacroGenics, Inc., Meira GTx LLC, Merck, Merus N.V., Numab Therapeutics AG, OncoCyte Corporation, Pfizer, Rakuten Medical, Inc., SIRPant Immunotherapeutics, Inc., Seagen, Inc., Vir Biotechnology, Inc.; Financial Interests, Personal, Other, Consultant: Adagene Incorporated, Aduro Biotech, Inc, Arcutis, Bicara Therapeutics, Inc, Brooklyn Immunotherapeutics LLC, Catenion, Dermavant, Everest Clinical Research Company, F. Hoffmann-La Roche Ltd., Fedoration Bio, Inc, Genocea Biosciences, Inc., Kowa Research Institute, Inc, Mirati Therapeutics, Inc, Nanobiotix, Novartis Pharmaceutical Company, Novasenta, PPD Development, L.P., Sanofi, Zymeworks, Inc.; Financial Interests, Institutional, Advisory Board: Eisai Europe Limited; Financial Interests, Personal, Other, Data Safety Monitoring Board: Mirror Biologics, Inc.; Financial Interests, Personal, Officer: Novasenta; Financial Interests, Personal, Stocks/Shares: Novasenta; Financial Interests, Institutional, Invited Speaker: AbbVie; Financial Interests, Institutional, Other, PI: Arcutis, AstraZeneca/MedImmune, BI, Bristol Myers Squibb, Castle Biosciences, Dermavant, Merck, Eli Lily, Galderma, InflaRx, Novartis, Novasenta, Regeneron, Tesaro, Amgen, DermTech, Janssen. U. Keilholz: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: MerckSerono, Novartis, AstraZeneca, Pfizer; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MerckSerono, MSD; Financial Interests, Personal, Other, Support for attending meetings and/or travel: MerckSerono. A. Psyrri: Financial Interests, Personal, Invited Speaker: MSD, Merck Serono; Financial Interests, Personal, Advisory Board: Pfizer, Sanofi, MSD, AstraZeneca, BMS, LEO, Rakuten, eTheRNA immunotherapies, Merck Serono; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Iovance, Pfizer, Pfizer, Roche, GENESIS, GSK, MSD, Incyte, Amgen, Debiopharm, Jannsen, Lilly, Regeneron, Sanofi, BI, Roche, Peregrine, Oncolytics Biotech; Financial Interests, Invited Speaker: AstraZeneca, KURA ONCOLOGY; Financial Interests, Institutional, Invited Speaker: Kura Oncology, Novartis, Replimmune; Financial Interests, Personal and Institutional, Funding: Kura Oncology, BMS, Roche, DEMO, Amgen, BI, GENESIS, BMS, Pfizer, Oncolytics Biotech; Financial Interests, Institutional, Funding: Merck Serono, Pfizer; Financial Interests, Personal, Other, Educational activity: Medscape, PrimeOncology; Non-Financial Interests, Project Lead, Medical Education with honoraria: Medscape. B. Keam: Financial Interests, Personal, Invited Speaker: Merck, Lily, MSD Oncology, AstraZeneca, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Handok, TrialInformatics, ImmunOncia, NeoImmunetech, Beigen. P. Bossi: Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, Sanofi, SunPharma, GSK, Molteni, Angelini, Nestlè; Financial Interests, Institutional, Invited Speaker: MSD, GSK, Pfizer, Kyowa Kyrin; Non-Financial Interests, Leadership Role, National research group - Board of Directors: GONO; Non-Financial Interests, Leadership Role, Board of Directors: MASCC. R. Metcalf: Financial Interests, Personal, Other, Consulting fees: Bayer, Aptus Clinical, PCI Biotech, Oxsonics Payment to individual; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Bristol Myers Squibb (BMS), Merck Sharp and Dohme (MSD), Bayer, Sanofi; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Bristol Myers Squibb (BMS); Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Bayer, Achilles Therapeutics, Ayala Pharmaceuticals. O. Serrano: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. P. Kaur: Financial Interests, Personal, Other, Former employee: AstraZeneca. D. Ruscica: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R.B. Cohen: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Consulting or advisory role: Cantargia AB, AstraZeneca, FStar Therapuetics, Coherus Biosciences, Ono Pharmaceutical, Actuate Therapeutics; Financial Interests, Institutional, Research Grant: Innate Pharma, Xencor, AstraZeneca, F-Star Biotechnology, Macrogenics, . All other authors have declared no conflicts of interest.