Abstract 172P
Background
JTX-8064, a highly selective and potent IgG4 inhibitor of myeloid-specific Leukocyte Immunoglobulin Like Receptor B2 (LILRB2), leads to macrophage reprogramming from an immunosuppressive to an immune activated state, resulting in T cell activation. INNATE (NCT04669899) is a phase (P) 1/2 dose escalation/expansion study of two investigational agents, JTX-8064 monotherapy (mono) and combination (combo) with pimi. P1 data defining Recommended P2 Dose (RP2D) are presented.
Methods
Pts with advanced solid tumors who progressed after all available therapy were treated at 7 dose levels of JTX-8064 mono IV q3w (50, 150, 300, 450, 600, 900, 1200 mg) and 2 dose levels of JTX-8064 (700, 1200 mg) + pimi 500 mg IV q3w using Bayesian design. 1o objectives: safety, tolerability, RP2D. 2 o objectives: receptor occupancy (RO), PK, immunogenicity. Objective response rate (RECIST 1.1) was exploratory.
Results
31 pts were treated in dose escalation, 22 JTX-8064 mono, 9 JTX-8064 + pimi. No dose limiting toxicities; maximum tolerated dose not reached. Safety: Mono: Median age 67. Eleven pts (50%) had treatment-related adverse events (TRAE). Most common were fatigue (n= 5), upper abdominal pain, arthralgia, flushing, nausea, and pyrexia (n= 2 each). The only Grade 3 (G3) TRAE and only serious related AE (SRAE) was tumor flare at 1200 mg. Combo: Median age 63. Six pts (66.7%) had TRAE, most common fatigue (n=4) and pyrexia (n=2). No ≥ G3 TRAEs, no SRAEs. PK was linear. Full RO thru 21 days was achieved at ≥ 300 mg. RP2D of 700 mg q3w was selected for JTX-8064 +/- pimi to optimize RO in tumor, with Cmin at steady state 63.4 (26.0-139.7) ug/mL. Treatment induced antibodies to JTX-8064 occurred in 1 mono and no combo pts. P1 Efficacy: Mono: 0 PR, 7 SD with 2 durable SD (appendiceal cancer 8.3, ovarian cancer 12.2 mo). Combo: 1 PR (6.2 mo) at 700 mg in PD-1i resistant cholangiocarcinoma with resolution of both bone pain and cachexia, 3 SD with 1 durable SD (post-PD-1i NSCLC 6 mo).
Conclusions
JTX-8064 was well-tolerated as mono and with pimi, with 700 mg q3w selected as the preliminary RP2D. Enrollment is ongoing in P2, including cohorts in renal and ovarian cancer that have met Simon’s 2-stage response criteria to expand.
Clinical trial identification
NCT04669899.
Legal entity responsible for the study
Jounce Therapeutics, Inc.
Funding
Jounce Therapeutics, Inc.
Disclosure
K. Papadopoulos: Financial Interests, Personal, Advisory Board: Turning Point Therapeutics, Bicycle, Basilia; Financial Interests, Institutional, Full or part-time Employment: START; Financial Interests, Personal, Ownership Interest: START; Financial Interests, Institutional, Invited Speaker, For conduct of clinical trial: 3D Medicines, AbbVie, ADC Therapeutics, Amgen, Anheart Therapeutics, Bayer, Daiichi Sankyo, EMD Serono, F-Star, Incyte, Jounce Therapeutics, Lilly, Linnaeus Therapeutics, Merck, Mersana, Mirati Therapeutics, Pfizer, Regeneron Pharmaceuticals, Revalution Medicines, Syros Pharmaceuticals, Tempest Therapeutics, Treadwell Therapeutics. T. Li: Financial Interests, Institutional, Research Grant: Merck, OncC4, LabyRx Immuno-Oncology, Genentech, Novartis, AbbVie Inc., Astelas, Atlas Medx, AstraZeneca, EMD Serono, RasCal, Jounce, Coherus, Jiangsu Hengrui, Tempus, Lung Cancer Mutation Consortium. N. Lakhani: Financial Interests, Personal, Advisory Board: Innovent Biologics; Financial Interests, Personal, Advisory Board, Participation in Ad Board: Ikena, SK Life Sciences; Financial Interests, Institutional, Invited Speaker: ALX Therapeutics, Ascentage, Constellation Pharma, Alpine Biosciences, Forty Seven, Merck, Pfizer, Regeneron, Symphogen, InhibRx, Seagen, Sapience Therapeutics, Jounce, Northern Biologics, Odonate, Loxo/Lilly, Ikena, Mersana Therapeutics, Astellas, Celgene, Helsinn, Shattuck Labs, Samumed, Glaxo Smith Kline, Alkermes, Servier, Samumed, Tizona Therapeutics, Gilead, Repare Therapeutics, Alkermes, InhibRx. J. Powderly: Financial Interests, Personal, Other, Consulting: Boxer Capital; Financial Interests, Personal, Invited Speaker, Consulting: Aavocyte; Financial Interests, Personal, Invited Speaker, Founder and Owner: Carolina BioOncology Institute, Pllc, BioCytics Inc.; Financial Interests, Personal, Ownership Interest, Founder and Owner: BioCytics Inc.; Financial Interests, Personal, Ownership Interest, Founder and Owner of phase 1 cancer research clinic: Carolina BioOncology Institute, PLLC; Financial Interests, Personal, Other, Founder and Owner, developing intellectual property for cellular therapies: BioCytics Inc; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb, Cullinan, Genentech/Roche, AstraZeneca/MedImmune, EMD Serono, Macrogenics, InCyte, Top Alliance BioSciience, Seattle Genetics, AbbVie, FLX Bio, Alkermes, Arcus BioSciences, Tempest Therapeutics, Calico Life Sciences, Apros, Jounce Therapeutics, Atreca, Sequenom, Repertoire Immune Medicines, Molecular Templates, I-MAB Pharma, NexCure, Xilio Therapeutics, Immune-Onc, Trethera, Zenshine Pharma, Adagene, BJ BioScience, Fate Therapeutics, Conjupro BioTherapeutics; Financial Interests, Institutional, Funding: Precision for Medicine, MT Group, Stemcell Technologies, Replimmune, Merck, Xilis; Financial Interests, Personal and Institutional, Funding: Pioma; Financial Interests, Personal and Institutional, Invited Speaker, Also funding for contract laboratory services: Nuvation; Other, Personal, Other, As Founder and Owner of BioCytics Inc. developing immune cellular therapy: BioCytics Inc. T. George: Financial Interests, Personal, Advisory Board: Pfizer Oncology, Tempus Labs; Financial Interests, Institutional, Invited Speaker: BMS, AZ, Lilly, Bayer, Incyte, Ipsen, Seagen, Genentech, Astellas, GSK, BioMed Valley Discoveries, Amgen, OncoC4, Jounce. D.G.K. Teoh: Financial Interests, Institutional, Invited Speaker: Jounce, Glaxo Smith Kline, Moderna. D. Kilari: Financial Interests, Personal, Invited Speaker: Astellas, Janssen, Pfizer, Aveo Oncology; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Institutional, Invited Speaker: Exelixis, Genentech, Jounce. G. Giaccone: Financial Interests, Personal, Advisory Board: Sanofi, Eisai, Spectrum; Financial Interests, Personal, Full or part-time Employment: Amgen. R.E. Sanborn: Financial Interests, Personal, Advisory Board: AstraZeneca, EMD Serono, Daiichi Sankyo, Lilly, Janssen Oncology, Macrogenics, Sanofi Aventis, Regeneron, Mirati Therapeutics, GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: Amgen, GlaxoSmithKline, Janssen Oncology; Financial Interests, Institutional, Funding, Funding for investigator-sponsored trial: Merck, AstraZeneca; Financial Interests, Institutional, Other, Institutional research support: BMS; Financial Interests, Institutional, Funding, Clinical trial funding: Jounce. S. Ghamande: Financial Interests, Personal, Invited Speaker: Esai; Financial Interests, Personal, Advisory Board, also invited speaker: GSK; Financial Interests, Institutional, Invited Speaker, Clinical trial payments: GSK, Jounce; Financial Interests, Institutional, Invited Speaker, Clinical trial payment: Merck, Esai; Financial Interests, Institutional, Invited Speaker, clinical trial payments: Mersana, AstraZeneca; Non-Financial Interests, Personal, Advisory Role: GOG foundation. P. LoRusso: Financial Interests, Personal, Advisory Board: AbbVie, Genmab, Genentech, CytomX, Takeda, Cybrexa, Agenus, IQVIA, TRIGR, Pfizer, ImmunoMet, Black Diamond, Glaxo-Smith Kline, QED Therapeutics, AstraZeneca, EMD Serono, Shattuck, Astellas, Salarius, Silverback, MacroGenics, Kyowa Kirin, Kineta, Zentalis, Molecular Templates, ABL Bio, STCube, Bayer, Seagen, imCheck, Relay Therapeutics, Stemline, Compass BADX, Mekanist, Mersana, BAKX Therapeutics, Scenic Biotech, Qualigen, Roivant Sciences, NeuroTrials; 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, Advisory Board, Advisory Board & Consultant: I-Mab; Financial Interests, Personal, Stocks/Shares: BAXK; Financial Interests, Institutional, Invited Speaker: AbbVie, ADC Therapeutics, ALX Oncology, Astellas Pharma, Astex Pharmaceuticals, AstraZeneca, Bayer, Black Diamond, Boehringer Ingelheim, Calico Life Sciences, Corvus Pharmaceuticals, CytomX Therapeutics, Eisai Pharmaceuticals, Eli Lilly, EMD Sernono, Five Prime, FLX Bio, F-Star Delta Limited, Genentech, Genmab, Incyte, Linnaeus Therapeutics, MedImmune, Merck Sharp & Dohme, Moderna Therapeutics, NextCure, Pfizer, Ribon Therapeutics, Sotio, Stemline Therapeutics, Takeda, Tesaro, Jounce; Non-Financial Interests, Personal, Other, AACI Clinical Research Innovation Steering Committee - Member: Association of American Cancer Institutes; 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, 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, Other, Chair - Phase 0 Task Force: American Association of Cancer Research; 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, External Advisory Board - Member: University of Arizona; Other, Personal, Other, External Scientific Advisory Board - Member: University of New Mexico; Other, Personal, Other, Scientific External Advisory Board - Member: University of California at San Diego. G. Gibney: Financial Interests, Personal, Advisory Board, Limited Consultant Role: Bristol Myers-Squibb, Merck, Lyell, Eisai, Regeneron, Genentech, Sapience Therapeutics; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Advisory Board, Consultant for data monitoring committee: Huyabio; Financial Interests, Personal, Advisory Board, Limited role on data monitor committee: Exicure; Financial Interests, Institutional, Invited Speaker, Support for investigator initiated trial: Exelixis, Lucerno Dynamics; Financial Interests, Institutional, Invited Speaker, Support for clinical trial: Jounce. V.T. Ma: Financial Interests, Institutional, Invited Speaker: Jounce Therapeutics; Non-Financial Interests, Personal, Principal Investigator: Jounce Therapeutics. K. Yalamanchili: Financial Interests, Institutional, Invited Speaker, Clinical trial funding: Jounce Therapeutics. J. Brown: Financial Interests, Personal, Invited Speaker, Speaker's Bureau for Avelumab: EMD Serono; Financial Interests, Personal, Invited Speaker, Speaker for MSL Training: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Jounce Pharmaceuticals, Seattle Genetics, Novita, Bicycle Therapeutics. N. Mota: Financial Interests, Personal, Stocks/Shares: Jounce Therapeutics. C. Tasillo Kadra: Financial Interests, Personal, Stocks/Shares: Jounce Therapeutics. B. Umiker: Financial Interests, Personal, Full or part-time Employment, I am an employee of Jounce Therapeutics: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, I have shares of Jounce Therapeutics: Jounce Therapeutics. X. Xiao: Financial Interests, Personal, Invited Speaker, Employee: Jounce Therapeutics; Financial Interests, Personal, Full or part-time Employment, Full time employee with stock options: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, have stock options: Jounce Therapeutics. E. Trehu: Financial Interests, Personal, Chief Medical Officer: Jounce Therapeutics, Inc.; Financial Interests, Personal, Invited Speaker, Member of the Board of Directors until Constellation was acquired in 2021: Constellation Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Jounce Therapeutics, Inc.