Abstract 758P
Background
Single agent ICIs are largely ineffective in treating ovarian cancer due to suppressive roles of Tregs, Myeloid Derived Suppressor cells (MDSCs), and the tumor extracellular matrix (ECM). The collagen dense ECM forms a barrier that blocks immune cell entry, suppresses immune cell activation and promotes ICI resistance. NC410, a novel therapeutic agent consisting of a dimeric LAIR-2 protein fused to a human IgG1 Fc domain, targets and remodels collagen, enhancing immune cell infiltration and blocks LAIR-1-mediated suppression by preventing binding to its ligand, collagen. In preclinical studies, NC410 combined with anti-PD-1/PD-L1 therapies demonstrated enhanced immune cell infiltration into the TME, increased immune function and improved antitumor activity.
Methods
An open-label, Phase 1b study was initiated to evaluate NC410 in combination with pembrolizumab for advanced solid tumors. In this study, 18 patients with MSS/MSI-L ovarian cancer received a fixed pembrolizumab dose of 400 mg every 6 weeks on Day 1, along with escalating doses of NC410: 60 mg for 2 patients, 100 mg for 14 patients, and 200 mg for 2 patients, administered every 2 weeks on Days 1, 15, and 29 of a 42-day cycle. The dosing followed a modified Toxicity Probability Interval (mTPI) design. The data reported here have a cut-off date of May 1, 2024.
Results
Of the 18 patients treated, 2 were ICI refractory and 16 ICI naïve. Amongst the 16 ICI naïve patients across all dose levels, the median lines of prior therapy were 5 (range 1-12). Eight patients are currently evaluable {2 confirmed PRs amongst the 3PRs: 7.9mo (200mg NC410), 4.3+mo (100mg NC410), 4.1mo (100mg NC410), 5 PD}. Two of the 3 subjects with PRs had liver metastases. The therapy was found to be safe and tolerable with manageable Gr≥3 treatment emergent (25%) and related (6%) adverse events. Blood immunophenotyping showed on-treatment early reduction of circulating active T cells and lower baseline and on-treatment MDSCs in PR subjects. Dose optimization of NC410 (100mg and 200mg) is being done to identify a RP2D and comprehensive data will be reported at the meeting.
Conclusions
NC410 in combination with pembrolizumab provides clinical benefit in advanced metastatic ovarian cancer, including those with liver metastasis.
Clinical trial identification
NCT05572684.
Editorial acknowledgement
Legal entity responsible for the study
NextCure, Inc.
Funding
NextCure, Inc.
Disclosure
E. Zsiros: Financial Interests, Personal, Advisory Board, Advisory board: Arsenal Bio; Financial Interests, Personal, Advisory Board: Merck, Nurix; Financial Interests, Research Grant, Merck is funding tranlsational work in one of my clinical trials: Merck. E.S. Christenson: Financial Interests, Personal, Advisory Board, Consultant for Seres Therapeutics: Seres Therapeutics; Financial Interests, Personal, Advisory Board, Advisory board: SIRTex therapeutics; Financial Interests, Institutional, Coordinating PI, PI on a trial for NextCure: NextCure; Financial Interests, Institutional, Research Grant, Research grant from Pfizer: Pfizer; Financial Interests, Institutional, Coordinating PI, PI for clinical trial with Regeneron: Regeneron; Financial Interests, Institutional, Local PI, PI for clinical trial: Affimed Gmbh. D. Sohal: Financial Interests, Personal, Invited Speaker: InCyte, Seagen, AstraZeneca; Financial Interests, Personal, Advisory Board: Totus, Regeneron, Elevar; Financial Interests, Institutional, Trial Chair: Ability Pharma, AstraZeneca; Financial Interests, Institutional, Local PI: Amgen, Apexigen, Astellas, Bexion, BMS, FibroGen, Genentech, Hengrui, Merck, Mirati, NextCure, PanCAN, Regeneron, Roche. S. Manda: Financial Interests, Personal, Advisory Board, Scientific advisor: Reglagene; Financial Interests, Personal, Stocks/Shares: Reglagene. S. Fu: Financial Interests, Institutional, Research Grant, Partial grant funding supporting facilities necessary for clinical trials.: NIH/NCI P30CA016672 – Core Grant (CCSG Shared Resources); Financial Interests, Institutional, Local PI: Abbisko, Antengene, BeiGene, Ltd, BeyondSpring Phamaceuticals, Inc., BioAtla, LLC., Boehringer Ingelheim, CUE Biopharma, Inc., Deka Biosciences, Eli Lilly & Co., Exelixis, Greenfire Bio, Inc., Hookipa Biotech, ImmavRx, Inc. (IMV), Innovent Biologics, Co., Ltd., Jazz Pharmaceuticals, K-Group Beta, Lantern Pharma Inc., Lyvgen Biopharm, Co., Ltd., MacroGenics, MediLink Therapeutics, Co. Ltd., Millennium Pharmaceuticals, inc., Nerviano Medical Sciences, NeuPharma, Inc., NextCure, Inc., Ningbo NewBay Technology Development Co., Ltd., Novartis, NovoCure, Nykode Therapeutics, Parexel International, LLC, PharmaMar USA, Inc., Pionyr Immunotherapeutics, Inc., PureTech Health, LLC, Qurgen, Inc., Sellas Life Sciences Group, Shanghai Huaota Biopharmaceutical Co., Ltd., Soricimed Biopharma, Inc., SQZ Biotechnologies, Sumitomo Dainippon, Taiho Oncology and NCCN, Treadwell Therapeutics, Turnstone Biologics, Tyligand Bioscience, Ltd., Virogin Biotech, Ltd.. A. Martz: Financial Interests, Personal, Full or part-time Employment: NextCure, Inc; Financial Interests, Personal, Stocks/Shares: NextCure, Inc. M. Zika: Financial Interests, Personal, Full or part-time Employment: NextCure; Financial Interests, Personal, Stocks/Shares: NextCure. S. Kordahi: Financial Interests, Personal, Full or part-time Employment, Senior Director, Clinical Operations: NextCure, Inc.; Financial Interests, Personal, Stocks/Shares, Stock Options Grant: NextCure, Inc.. P. Kothari: Financial Interests, Institutional, Full or part-time Employment: NextCure. S. Kahan: Financial Interests, Personal, Full or part-time Employment, Employeed by NextCure, Inc,: NextCure, Inc. E.A. Barbu: Financial Interests, Institutional, Full or part-time Employment: NextCure, Inc.; Financial Interests, Personal, Stocks/Shares: NextCure, Inc.; Non-Financial Interests, Institutional, Proprietary Information: NextCure, Inc.. A. Morawski: Financial Interests, Institutional, Full or part-time Employment: NextCure, Inc.; Financial Interests, Institutional, Stocks/Shares, Granted Stock Options: NextCure, Inc.. D. Flies: Financial Interests, Personal, Full or part-time Employment: NextCure; Financial Interests, Personal, Stocks/Shares: NextCure. S.A.R. Langermann: Financial Interests, Institutional, Full or part-time Employment, CSO: NextCure, Inc.; Financial Interests, Institutional, Stocks/Shares: NextCure, Inc.. M. Chisamore: Financial Interests, Institutional, Full or part-time Employment: Merck & Co. Inc; Financial Interests, Institutional, Stocks/Shares: Merck & Co. Inc. U. Guha: Financial Interests, Personal, Full or part-time Employment, employee of NextCure Inc.: NextCure Inc.; Financial Interests, Personal, Stocks/Shares, current employee stock options: NextCure Inc.; Financial Interests, Personal, Stocks/Shares, Prior employee of TCR2 Therapeutics- now Adaptimmune: TCR2/Adaptimmune. H. Myint: Financial Interests, Personal, Full or part-time Employment, Chief Medical Officer: NextCure Inc; Financial Interests, Personal, Stocks/Shares: NextCure Inc. All other authors have declared no conflicts of interest.
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