1038P - A phase II trial of the IO102-IO103 vaccine plus pembrolizumab: preliminary analysis for first-line (1L) treatment of non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN)

Background

The IO102-IO103 vaccine is an investigational first-in-class, dual-antigen, immune-modulatory therapy that stimulates activation of T cells against IDO+ and/or PD-L1+ cells in cancer, resulting in potentially increased susceptibility to anti-PD-1 blockade. Treatment with IO102-IO103 plus nivolumab in anti-PD-1 naïve metastatic melanoma shows high clinical activity and is well tolerated ( Kjeldsen, Nat Med 2021). Thus, there is strong rationale for combining IO102-IO103 and anti-PD-1 therapy in 1L treatment of NSCLC and SCCHN.

Methods

This is a phase 2, non-comparative, open-label, multi-cohort trial (EudraCT No. 2021-003026-69; ClinicalTrials.gov No. NCT05077709). Patients (pts) with no prior treatment for metastatic disease are being enrolled: metastatic NSCLC, with PD-L1 tumor proportion Score ≥50% (Cohort A); recurrent or metastatic SCCHN with PD-L1 combined positive scores ≥20 (Cohort B). Pts receive 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 intravenous pembrolizumab (200 mg on D1), for ≤2 years. Primary endpoint is overall response rate by RECIST 1.1., with secondary endpoints including safety.

Results

At data cut-off (April 12, 2023) 15/22 and 4/6 enrolled pts were efficacy evaluable (≥2 full cycles of treatment and ≥1 scan) in Cohorts A and B, respectively. Eleven and two patients had 2 or more scans in Cohort A and B. In Cohort A, 8 pts (53.3%) had a partial response (PR; 4 confirmed), while 5 had stable disease; 2 pts had progressive disease (PD). In Cohort B, 2 pts (50%) had a PR (1 confirmed) and 2 pts had PD. For the 28 treated pts, any grade treatment-related adverse events (TRAEs) occurred in 17 (60.7%) with 1 (3.6%) being serious. Most common TRAE reported was injection site reactions (n=8; 28.6%).

Conclusions

This preliminary analysis suggests combining IO102-IO103 and pembrolizumab in pts with metastatic NSCLC and recurrent/metastatic SCCHN is tolerable, with encouraging clinical activity, and supports further development. Enrollment is ongoing. Additional clinical and biomarker data from trial patients are planned to be presented at the meeting.

Clinical trial identification

EudraCT: 2021-003026-69 Start date: 2022-05-09 (date of competent authority decision) Date on which this record was first entered in the EudraCT database: 2021-12-14 ClinicalTrials.gov Identifier: NCT05077709.

Editorial acknowledgement

Medical writing and editorial support for the development of this abstract, under the direction of the authors, were provided by Edward Potts and Sherriden Beard of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

IO Biotech.

Funding

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

Disclosure

J.W. Riess: Financial Interests, Personal and Institutional, Advisory Role: Blueprint, Novartis, Boehringer, Ingelheim; Financial Interests, Institutional, Research Funding: Merck, Novartis, Spectrum, Revolution Medicine, AstraZeneca, GSK; Other, Personal, Advisory Board: Blueprint; Financial Interests, Personal, Advisory Board: BeiGene, Daiichi Sankyo, EMD Serano, Turning Point, Janssen, BMS. E. Cohen: Financial Interests, Personal, Leadership Role: Kura, Akamis Bio, Kinnate Biopharma, Pangea Therapeutics; Financial Interests, Personal, Stocks or ownership: Kinnate Biopharma, Pangea Therapeutics; Financial Interests, Personal, Advisory Role: Adagene, Astellas, Cidara, Eisai, Genmab, Gilboa, iTeos, Eli Liily, MSD, Merck, Nectin Tx, Novartis, Nykode, Pangea Therapeutics, PCI Bioteck. J. Spicer: Financial Interests, Institutional, Advisory Board, Compensation to my employer for time providing advice: Lilly, AstraZeneca, BMS, GSK, RS Oncology; Financial Interests, Personal, Stocks/Shares, Co-founder: Epsilogen; Financial Interests, Institutional, Local PI, Reimbursement for treatment of patients in trial: Achilles, Genmab, Roche, Seattle Genetics, Trizell, BergenBio, MSD, Gilead; Financial Interests, Institutional, Coordinating PI, Reimbursement for treatment of patients in trial: Starpharma, BMS, IO Biotech, RS Oncology; Non-Financial Interests, Member of Board of Directors, 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 Expet Advisory Group on Oncology & Haematology. P.H. Shaw: Financial Interests, Personal, Other, Honoraria: Takeda BMS; Financial Interests, Personal, Advisory Role: Takeda BMS; Financial Interests, Personal, Speaker’s Bureau: AZ. L. Medina Rodríguez: Financial Interests, Personal, Other, Travel, accomodation, expenses: Novartis, Servier. M.F. Chaney: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co., Inc.; Financial Interests, Personal, Other, Travel, accommodations, expenses: Merck & Co., Inc.. S. O'Neill: Financial Interests, Personal and Institutional, Full or part-time Employment: IO Biotech, Autolus Ltd; Financial Interests, Personal, Stocks or ownership: IO Biotech, Autolus Ltd, Amgen; Financial Interests, Personal and Institutional, Other, Travel, accommodations, expenses: IO Biotech. A.W. Pedersen: Financial Interests, Personal and Institutional, Full or part-time Employment: IO Biotech. D. McDowell: Financial Interests, Personal and Institutional, Full or part-time Employment, Current: IO Biotech; Financial Interests, Personal and Institutional, Full or part-time Employment, Previous: BMS; Financial Interests, Personal, Leadership Role: IO Biotech; Financial Interests, Personal, Stocks or ownership: IO Biotech, BMS. E. Ehrnrooth: Financial Interests, Personal and Institutional, Full or part-time Employment: IO Biotech ApS; Financial Interests, Personal, Leadership Role: IO Biotech ApS; Financial Interests, Personal, Stocks or ownership: IO Biotech ApS. P. Garrido Lopez: Financial Interests, Personal, Full or part-time Employment: Teva; Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Takeda, Sanofi; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Janssen, MSD, Medscape, Novartis, Pfizer, Roche, Takeda, Touchlme; Financial Interests, Personal, Other: AstraZeneca, Roche. All other authors have declared no conflicts of interest.