1022P - A phase II trial of the IO102-IO103 vaccine plus pembrolizumab: Completed cohort for first-line (1L) treatment of advanced squamous cell carcinoma of the head and neck (SCCHN)

Background

Pembrolizumab monotherapy is approved for 1L PD-L1-positive (CPS ≥1%) recurrent/metastatic SCCHN; objective response rate (ORR) is low even in PD-L1-high (CPS ≥20%); (KEYNOTE-048; 23%). IO102-IO103 investigational vaccine targets tumor cells and immune-suppressive cells in the tumor microenvironment by potentiating anti-tumor activity via activation and expansion of T cells against indoleamine 2,3-dioxygenase 1 (IDO1) and PD-L1 positive cells. Combination of IO102-IO103/nivolumab in a phase 1/2 trial of anti-PD-1 naïve metastatic melanoma patients (pts) showed 80% ORR (50% complete response); was well tolerated, providing rationale for testing IO102-IO103/anti-PD-1 in 1L SCCHN. IO102-IO103/pembrolizumab is also under investigation for resectable SCCHN and melanoma; a phase 3 registration trial in advanced 1L melanoma is fully enrolled.

Methods

This phase 2, non-comparative, open-label, multi-centre, multi-cohort trial enrolled SCCHN pts with PD-L1 CPS ≥20%, any HPV status, and no prior systemic treatment for recurrent/metastatic disease. Pts received 3-week cycles of subcutaneous IO102-IO103 (85-85 μg on Day [D] 1 and 8 of Cycle 1 and 2, then D1 only) plus pembrolizumab (200 mg on D1) for ≤2 years. Primary endpoint was ORR by RECIST 1.1, with secondary endpoints including progression-free survival (PFS) and safety.

Results

At data cut-off (Apr 1, 2024), of 21 pts enrolled, one was ineligible and 18 had received ≥2 cycles of treatment and were considered evaluable for efficacy. Eight pts had a confirmed partial response (ORR 44%), four pts (22%) had stable disease and 6 (33%) had progressive disease. PFS at 6 months was 55.5% with two pts censored for <6 months follow-up. Treatment-related adverse events of any grade occurred in 15 of 21 pts (71.4%) including 3 (14.3%) grade ≥3 and none being serious, fatigue was most commonly reported (n=4; 19.0%).

Conclusions

IO102-IO103/pembrolizumab shows encouraging clinical activity for 1L treatment of PD-L1 high SCCHN. The combination is tolerable, with no unexpected safety signals. Updated ORR analysis, PFS, and exploratory biomarkers will be presented at the meeting.

Clinical trial identification

EudraCT 2021-003026-69; NCT05077709.

Editorial acknowledgement

Medical writing and editorial support for the development of this abstract were provided by Edward Potts and Beverly La Ferla of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

IO Biotech ApS & Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

IO Biotech ApS & Merck Sharp & Dohme Llc, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

J.W. Riess: Financial Interests, Personal, Advisory Role: Blueprint, Novartis, Boehringer Ingelheim; Financial Interests, Institutional, Research Funding: Merck, Novartis, Spectrum, Revolution Medicine, AstraZeneca, GSK; Financial Interests, Personal, Advisory Board: Blueprint, BeiGene, Daiichi Sankyo, EMD Serono, Turning Point, Janssen, BMS. J. Spicer: Financial Interests, Institutional, Advisory Board, Compensation to my employer for time providing advice: AstraZeneca, BMS, GSK, RS Oncology; Financial Interests, Personal, Stocks/Shares, Co-founder: Epsilogen; Financial Interests, Personal, Stocks/Shares: Avacta; Financial Interests, Institutional, Local PI, Reimbursement for treatment of patients in trial: Achilles, Roche, Trizell, BergenBio, MSD, Gilead, Iovance; Financial Interests, Institutional, Coordinating PI, Reimbursement for treatment of patients in trial: Starpharma, BMS, IO Biotech, RS Oncology; Non-Financial Interests, Leadership Role, National strategy board: Experimental Cancer Medicine Centres; Non-Financial Interests, Member of Board of Directors, Steering Committee: British Thoracic Oncology Group; Non-Financial Interests, Advisory Role, Advice on licensing decisions for MHRA: CHM Expert Advisory Group on Oncology & Haematology; Non-Financial Interests, Advisory Role, Advice on regulatory approvals: CHM Cancer Vaccines Expert Working Group. T. Seiwert: Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Cue Biopharma, Kura, Merck, Nanobiotix, Regeneron, Roche; Financial Interests, Personal, Advisory Role, honoraria: Bayer, Cue Biopharma, Innate Pharma, IO Biotech, Merck, Nanobiotix, Nektar, Sanofi, VIR. V. Villaflor: Financial Interests, Personal, Advisory Role: AstraZeneca, Genentech/Roche, Bristol Myers Squibb, Novacure, Regeneron, Gilead. P.H. Shaw: Financial Interests, Personal, Financially compensated role, Honoraria: BMS, AZ, Takeda. A. Soria Rivas: Financial Interests, Personal, Advisory Role, Consulting: BMS, Merck Sharp & Dohme, Novartis Pharma, Immunocore, Sanofi Aventis, Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: BMS, Merck Sharp & Dohme, Novartis Pharma, Sanofi Aventis, Pierre Fabre; Financial Interests, Personal, Non financial benefits, Travel, Accommodation, Expenses: Pierre Fabre, Merck Sharp & Dohme. M. Chaney: Financial Interests, Personal, Full or part-time Employment: Merck and Co., Inc; Financial Interests, Personal, Stocks/Shares: Merck and Co., Inc; Non-Financial Interests, Member: ASCO, AACR. C. Abildgaard: Financial Interests, Personal, Full or part-time Employment: IO Biotech; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting role: AnRes Clinical. P. Patel: Financial Interests, Personal, Full or part-time Employment: IO Biotech. M. Iglesias: Financial Interests, Personal, Full or part-time Employment: IO Biotech; Financial Interests, Personal, Stocks/Shares: IO Biotech. Q. Ahmad: Financial Interests, Personal, Full or part-time Employment: IO Biotech; Financial Interests, Personal, Stocks/Shares: IO Biotech, Novartis; Financial Interests, Personal, Non financial benefits, Travel, Accommodations, Expenses: IO Biotech, Novartis. D. McDowell: Financial Interests, Personal, Full or part-time Employment: IO Biotech; Financial Interests, Personal, Stocks/Shares: IO Biotech, BMS. P. Garrido Lopez: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Janssen, MSD, Touch Expert, Medscape; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Janssen, Lilly, MSD, Novartis, Roche, Takeda, Daiichi Sankyo, Sanofi, Amgen; Financial Interests, Personal, Advisory Board, Spouse: Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Janssen, Boehringer Ingelheim, Pfizer, Amgen, Nordic; Financial Interests, Personal, Other, Data monitoring committee for INC280I12201 trial in 2020: Novartis; Financial Interests, Personal, Steering Committee Member, CACZ885V2201C_CANOPY-N trial: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Local PI: Novartis, Janssen, AstraZeneca, Pfizer, Blueprint, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Steering Committee Member, IO102-012/KN-764 trial: IO Biotech; Financial Interests, Personal, Steering Committee Member, JNJ-61186372 (JNJ-372) Clinical Development Program: Janssen; Financial Interests, Institutional, Other, Spouse: Mitsubishi, AbbVie; Financial Interests, Institutional, Other, Spouse, clinical trial team: Janssen, Boehringer; Financial Interests, Personal, Steering Committee Member, JDQ443G12301 trial, Steering Committee member: Novartis; Non-Financial Interests, Leadership Role, Past Council member as Women for Oncology Committee Chair Past Fellowship and Award Committee and Press Committee Faculty for lung and other thoracic tumors: ESMO; Non-Financial Interests, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) 2020-2022Past President 2023-2024: FACME; Non-Financial Interests, Leadership Role, Former President of Spanish Medical Oncology Society: SEOM; Non-Financial Interests, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Board member: AECC; Non-Financial Interests, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member, Educational Committee member, Academy member: IASLC; Non-Financial Interests, Advisory Role, Member of the Spanish National Health Advisory Board: Spanish Minister of Health; Non-Financial Interests, Advisory Role, Assessment for lung cancer screening evaluation: EUnetHTA; Non-Financial Interests, Advisory Role: Spanish National Evaluation network (RedETS), member of the King Hussein Award’s Board of Directors; Non-Financial Interests, Advisory Role, scientific advisory group member for clinical immunological, oncology and lung cancer areas: EMA; Other, My son is working with the pharma company TEVA as an engineer. I do not have any relationship with TEVA. All other authors have declared no conflicts of interest.