First results from phase II dose expansion cohort of transcon IL-2 β/γ in combination with standard of care chemotherapy for platinum resistant ovarian cancer (PROC) in the IL Believe trial

BackgroundPROC is an area of high unmet medical need due to the generally poor outcomes and limited activity of standard systemic therapy. Clinical responses with TransCon IL-2 β/γ (TC-IL-2 β/γ, onvapegleukin alfa) +/- pembrolizumab in heavily pre-treated patients with anti-PD-(L)1 relapsed or refractory solid tumors have been reported (Starodub et al, ESMO23). Here, encouraging preliminary results from the PROC cohort are provided.MethodsIn this PROC cohort (progression within 6 months after completing prior platinum-based therapy), patients received the recommended phase 2 dose of 120 μg/kg TC-IL-2 β/γ IV Q3W plus physician’s choice of paclitaxel, docetaxel, or pemetrexed until disease progression or unacceptable toxicity. Disease response was assessed every 9 weeks per RECIST 1.1. Safety, efficacy, and biomarkers were evaluated.ResultsAs of 16Apr24, 12 patients were treated with TC-IL-2 β/γ in combination with chemotherapy (pemetrexed, n=7; paclitaxel, n=4 and docetaxel, n=1). Median prior lines of therapy were 5 (range 2-7), including prior anti-PD-(L)1 in 25% of patients. The most common Treatment Related Adverse Events (TRAEs) were fatigue (66.7%), nausea (41.7%), and neutropenia (33.3%). TRAEs ≥ Grade 3 were neutropenia (n=3), fatigue (n=2), decreased appetite, chronic inflammatory demyelinating polyneuropathy and thrombocytopenia (n=1 each). Out of 6 efficacy-evaluable patients as of 06May24, ORR is 33% per RECIST 1.1 (2 confirmed PRs, progression after 3 and 7 lines of prior systemic treatments). Preliminary biomarker analysis shows selective expansion of cytotoxic lymphocytes (CLs), without meaningful expansion of eosinophils and Tregs for at least 3 weeks after dosing.ConclusionsInitial data suggest that TC-IL-2 β/γ in combination with chemotherapy for PROC is generally well-tolerated with meaningful clinical responses in heavily pre-treated patients. Preliminary evaluation of biomarkers shows a sustained and specific expansion of CLs.Clinical trial identificationNCT05081609.Legal entity responsible for the studyAscendis Pharma.FundingAscendis Pharma.DisclosureO. Yeku: Financial Interests, Personal, Other, Consultant: GIMV NV, TigaTx Inc; Financial Interests, Personal, Advisory Board: hC Bioscience; Financial Interests, Personal, Full or part-time Employment, Associate Editor: NEJM Evidence; Financial Interests, Personal, Full or part-time Employment: Massachusetts General Hospital; Financial Interests, Personal, Other, Patent Pending: MUC16 Directed Antibodies for therapeutic applications; Financial Interests, Personal, Other, Patent pending: Human Artificial Chromosomes for therapeutic applications; Financial Interests, Institutional, Local PI: Ascendis Pharma A/S, Duality Biologics, Immunocore Limited, Merck Sharp & Dohme Corporation, ProfoundBio. J-Y. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation, Regeneron; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon, Regeneron, Ascendis Pharma, Advenchen, BMS, Kelun, Sutro; Financial Interests, Personal and Institutional, Local PI: BeiGene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: Ono, Takeda, GSK; Financial Interests, Institutional, Other, Sub I: Corcept. B. Rimmel: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, Immunogen, Merck. S-B. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiichi Sankyo, BeiGene, Samsung Bioepics, Obi Pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. T.F.A. Van Den Mooter: Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Expert Testimony: Astellas, Bayer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. G. Kichenadasse: Financial Interests, Personal, Full or part-time Employment: SOCRU; Financial Interests, Personal, Leadership Role: SOCRU. C. Krapp, S. Slavsky, S.M. Singel: Financial Interests, Personal, Full or part-time Employment: Ascendis Pharma. D. Torrejon Castro: Financial Interests, Personal, Full or part-time Employment: Ascendis Pharma Inc. V. Kwatra: Financial Interests, Personal, Advisory Board: Roche.