126P - Evaluation of Myeloid Targeting Agents, PY159 and PY314, in Two Dose Expansion Phase 1b Trials in Platinum-Resistant Ovarian Cancer

Background

Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells facilitate a hostile tumor microenvironment and are associated with worse clinical outcomes in PROC. We evaluated the safety and preliminary efficacy of PY159, an agonist antibody to TREM1 that reprograms immunosuppressive intratumoral myeloid cells and PY314, an antagonist antibody to TREM2 that depletes tumor associated macrophages, as a single agent and in combination with pembrolizumab in subjects with PROC.

Methods

PY159 and PY314 were individually evaluated in patients with PROC. Subjects were treated with monotherapy (PY159 3 mg/kg or PY314 10 mg/kg), based on the recommended dose for expansion derived from the Phase 1a studies. At the time of first progression, subjects could continue study drug and crossover to combination therapy with pembrolizumab (200 mg) every 3 weeks at the discretion of the investigator. Disease assessment by RECIST 1.1 was performed every 6 weeks.

Results

17 subjects were enrolled in the PY159 study (median age 67, range 22-77; median prior therapies 6, range 2-18) and 16 subjects in PY314 (median age 65.5, range 49-81; median prior therapies 4, range 2-18). 7 subjects in PY159 and 8 subjects in PY314 crossed over to combination therapy. Safety events included the following: TRAEs occurred in 9 (56.3%) subjects in PY314 and 15 (88.2%) in PY159. IRRs occurred in 3 (18.8%) subjects in PY314 and 6 (35.3%) in PY159. irAEs occurred in 1 (6.3%) subject in PY314 (diarrhea) and 13 (76.5%) in PY159 (arthralgias). SAEs occurred in 12 (75%) subjects in PY314 (all unrelated) and 6 (36.3%) in PY159 (1 related). The best radiographic response in PY159 was stable disease in 8/16 subjects (50%; median 16 weeks, range 9-33), and in PY314, it was stable disease in 8/16 subjects (50%; median 12 weeks, range 6-36). Median PFS was 2.76 months and 2.69 months in PY159 and PY314, respectively. There were no responses in the crossover arm.

Conclusions

Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as a single agent and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC.

Clinical trial identification

PY159: NCT04682431; PY314: NCT04691375.

Legal entity responsible for the study

The authors.

Funding

Pionyr Immunotherapeutics Inc.

Disclosure

O.O. 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, 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, Avenge Bio, Inc, Duality Biologics, Immunocore Limited, Merck Sharp & Dohme Corporation, Pionyr Immunotherapeutics Inc, ProfoundBio. J.S. Wang: Financial Interests, Personal, Invited Speaker, Previous Member of Speaker's Bureau for Tagrisso and Imfinzi, stopped in 2021: AstraZeneca; Financial Interests, Personal, Invited Speaker, Previous Member of Speaker's Bureau for Lenvima, stopped 2021: Eisai; Financial Interests, Institutional, Local PI: 7,8 Pharma, Accutar, Adagene, Artios Pharma, AstraZeneca, Blueprint, Boehringer Ingelheim, Celgene/BMS, Clovis Pharma, Cyteir, Daiichi Sankyo, Forty Seven, Genentech/Roche, Hotspot, ImmunoOnc, Janssen, Kymab, LSK BioPartners, MabSpace, Macrogenics, Moderna, Novartis, Nurix, ORIC, Olema Therapeutics, Prelude Therapeutics, Ribon Therapeutics, Syndax, Teneobio, Zymeworks; Financial Interests, Institutional, Coordinating PI: Astellas, Bayer Healthcare, BeiGene, Bicycle Therapeutics, BioNTech, BioTheryX, Biosplice, Cullinan, Erasca, GSK, H3 Biomedicine, Hutchinson MediPharma, IGM Biosciences, Immuno-Gen, Jazz Pharma, Klus Pharma, Medikine, NGM Bio, Phoenix Molecular Designs, Pionyr, PureTech Health, Revolution Medicines, Pyxis, Qilu Pugent Sound, Relay Therapeutics, Sanofi, StingThera, TopAlliance, Treadwell Therapeutics, Xencor. P. Lorusso: Financial Interests, Personal, Advisory Board: AbbVie, Genmab, Genentech, CytomX, Takeda, Cybrexa, Agenus, IQVIA, TRIGR, Pfizer, ImmunoMet, Black Diamond, GSK, QED Therapeutics, AstraZeneca, EMD Serono, Shattuck, Astellas, Salarius, Silverback, MacroGenics, Kyowa Kirin, Kineta, Zentalis, Molecular Templates, Bayer, ABL Bio, STCube, Relay Therapeutics, Stemline, Compass BADX, BAKX Therapeutics, Scenic Biotech, Qualigen, Roivant Sciences, NeuroTrials, Seagen, imCheck, Mekanist, Mersana; Financial Interests, Personal, Other, Data Safety Monitoring Board: Agios, Five Prime, Halozyme; Financial Interests, Personal, Other, imCORE Alliance: Roche-Genentech; Financial Interests, Personal, Other, Consultant: Sotio, SK Life; Financial Interests, Personal, Other, Data Safety Monitoring Committee: Tyme; Financial Interests, Personal, Stocks/Shares: BAXK; Financial Interests, Institutional, Local PI: AbbVie, ADC Therapeutics, Boehringer Ingelheim, ALX Oncology, Astellas Pharma, Astex Pharmaceuticals, AstraZeneca, Bayer, Black Diamond, Calico Life Sciences, Corvus Pharmaceuticals, CytomX Therapeutics, Eisai Pharmaceuticals, Eli Lilly, EMD Sernono, Five Prime, FLX Bio, F-Star Delta Limited, Genentech, MedImmune, Genmab, Incyte, Linnaeus Therapeutics, Merck Sharp & Dohme, Moderna Therapeutics, NextCure, Pfizer, Takeda, Ribon Therapeutics, Sotio, Stemline Therapeutics, Tesaro, Jounce; Financial Interests, Personal, Advisory Board, Advisory Board & Consultant: I-Mab; Non-Financial Interests, Personal, Other, AACR Methods in Clinical Cancer Research Workshop - Co-Director: American Association for Cancer Research; Non-Financial Interests, Personal, Other, AACR Annual Report Committee - Member: American Association for Cancer Research; Non-Financial Interests, Personal, Other, Continuing Medical Education Committee - Member: American Association for Cancer Research; Non-Financial Interests, Personal, Other, Molecular Cancer Therapeutics Editorial Board - Member: American Association for Cancer Research; Non-Financial Interests, Personal, Other, ASCO Conquer Cancer Young Investigator Award Grand Selection Committee - Member: American Society of Clinical Oncology; Non-Financial Interests, Personal, Other, Chair - Phase 0 Task Force: American Association of Cancer Research; Non-Financial Interests, Personal, Other, AACI Clinical Research Innovation Steering Committee - Member: Association of American Cancer Institutes; Non-Financial Interests, Personal, Other, New Drugs in Oncology Seminar Planning Committee - Member: American Society of Clinical Oncology; Non-Financial Interests, Personal, Other, New Agents Committee: Translational Research Panel - Chair: Cancer Research Unite Kingdom; Non-Financial Interests, Personal, Other, Scientific Advisory Board - Member: Targeted Anti-Cancer Therapies; Non-Financial Interests, Personal, Member: American Association for Cancer Research, ASCO; Other, Personal, Other, Investigational Drug Steering Committee - Committee Member: National Cancer Institute; Other, Personal, Other, Phase I Special Emphasis Panel - Grant Reviewer/Discussion Leader: National Cancer Institute; Other, Personal, Other, NeXT Special Emphasis Panel - Grant Reviewer: National Cancer Institute/National Institute of Health; Other, Personal, Other, Board of Scientific Counselors, Clinical Sciences & Epidemiology: National Cancer Institute; Other, Personal, Other, Young Investigator Meeting, Cancer Therapy Evaluation Program - Professor: National Cancer Institute; Other, Personal, Other, Academic Advisory Board SPORE GI Malignancies - Case Western Reserve University: Case Western Reserve University; Other, Personal, Other, Scientific External Advisory Board - Member: University of California at San Diego; Other, Personal, Other, External Advisory Board - Member: University of Arizona; Other, Personal, Other, External Scientific Advisory Board - Member: University of New Mexico. A. Naqash: Financial Interests, Personal, Other, Social Media Editor and Consultant: JCO Precision Oncology; Financial Interests, Institutional, Local PI: Loxo, Surface Oncology, ADC Therapeutics, IGM Biosciences, Nikang Therapeutics, Inspirna, Revolution Medicine, Jacobio, Pionyr, Jazz, NGM; Financial Interests, Institutional, Coordinating PI: EMD Serono, Aravive; Non-Financial Interests, Personal, Other, Social Media Consultant and Scientific Committee Member: ASCO; Non-Financial Interests, Personal, Other, Educational Activity: OncLive; Non-Financial Interests, Personal, Leadership Role, Scientific Committee Co-Chair: ORIEN; Non-Financial Interests, Personal, Leadership Role, Early Career Scientist Committee: SITC. J. Hubbard: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: Incyte, Bayer, BeiGene; Financial Interests, Institutional, Local PI: Boston Biomedical, Senhwa Biosciences, Bayer, Merck, Hutchison MediPharma, Seattle Genetics, Tovogene, TriOncology, Incyte, Pionyr, G1 Therapeutics, eFFECTOR Therapeutics, Roche; Financial Interests, Institutional, Coordinating PI: Taiho Pharmaceutical, TreoBio. S. Kummar: Financial Interests, Personal, Advisory Board: Bayer, Gilead, Mundibiopharma, Boehringer Ingelheim, Springworks Theraepeutics, HarbourBiomed, Boehringer Ingelheim, Oxford BioTherapeutics; Financial Interests, Personal, Advisory Board, Spouse: Cadila Pharmaceuticals; Financial Interests, Personal, Other, Chair, DSMC: Mirati; Financial Interests, Personal, Advisory Board, Consultant: Genome Insight; Financial Interests, Personal, Ownership Interest: Pahtomiq; Financial Interests, Personal, Ownership Interest, Spouse (co-founder): Arexeon; Financial Interests, Personal, Other, co-founder: Pathomiq; Financial Interests, Institutional, Local PI: ADC Therapeutics, Pionyr Therapeutics, Eisai, Bristol Myers Squibb, Syndax, SeaGen, ORIC, EMD Serono, Genome & Company, Moderna, Amgen, Elevation Oncology, VelosBio Inc, Gilead, Day One Biopharmaceuticals, ASTX Therapeutics, PMV Pharmaceuticals, Vincerx Pharma, Inc; Financial Interests, Institutional, Local PI, trial funding: 23&Me. C.E. Kyriakopoulos: Financial Interests, Personal, Advisory Board: Exelixis, AVEO, Sanofi-Aventis, EMD Serono, Janssen Pharmaceuticals; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Stocks/Shares: Biogen, Epic Systems; Financial Interests, Institutional, Local PI: Gilead, Incyte Corporation, Sanofi-Aventis, AstraZeneca. E. Schenk: Financial Interests, Personal, Invited Speaker: OncLive, Ideology Health, MJH Life Sciences, Sanofi, MedPro, Janssen; Financial Interests, Personal, Advisory Board: Prescient Advisory, G1 Therapeutics, Regeneron, BioAtla; Non-Financial Interests, Personal, Other, Expert member, NSCLC guidelines panel: ASCO. All other authors have declared no conflicts of interest.