Abstract 125P
Background
PT-112 is an immunogenic small molecule with reported clinical activity. In preclinical models, it induces ICD and synergizes with immune checkpoint inhibitors. Monotherapy and avelumab combination dose escalation studies have shown PT-112 to be well-tolerated. The recommended phase 2 dose was established at 360 mg/m2 (days 1, 8 and 15) when combined with 800 mg of avelumab (days 1 and 15) over a 28-day cycle. Here, we present safety and efficacy findings from the phase 2a PAVE cohort in metastatic NSCLC.
Methods
NSCLC pts were eligible following no more than 4 prior lines of therapy (requiring prior anti-PD-(L)1 and platinum treatment). Correlative sampling included baseline tumor biopsy profiling and blood T cell receptor sequencing.
Results
Eighteen pts were enrolled. Common treatment-related adverse events (TRAEs) were anemia (50%), fatigue (50%), thrombocytopenia (44%), nausea (44%) and anorexia (44%). 72% of pts had ≥1 grade 3-4 TRAEs. Treatment-related peripheral neuropathy was noted in 4 pts (22%). There were 5 cases (28%) of infusion-related reactions, which led to the discontinuation of avelumab in two. Of the 15 pts evaluable for efficacy, 6 pts (40%) had stable disease by iRECIST. Two cases of radiographic and clinical improvement were noted: one pt with primary resistance to prior therapy (nivolumab, ipilimumab, carboplatin and gemcitabine) had a complete response in target and non-target lesions and relief of pulmonary symptoms before experiencing single nodal progression; another pt experienced a multi-site FDG-PET response and remained stable with a PFS of 7.3 months. Both pts had PD-L1 TPS of 5% and 10%, respectively; MSS; and TMB <10. Furthermore, the study population experienced a significant increase in the fraction of T cells within total nucleated blood cells while on treatment.
Conclusions
PT-112 in combination with avelumab was safe and AEs were manageable. Evidence of drug activity was observed, including meaningful clinical benefit in pretreated patients without known predictive markers for immunotherapy response. These results support further study of PT-112 combinations in NSCLC, and assessment of PT-112’s immunological effects in pts.
Clinical trial identification
NCT03409458.
Legal entity responsible for the study
Promontory Therapeutics Inc.
Funding
Promontory Therapeutics Inc.
Disclosure
M. Imbimbo: Financial Interests, Institutional, Invited Speaker: Infomedica; Non-Financial Interests, Personal, Principal Investigator: BMS, MedImmune; Non-Financial Interests, Personal, Other, Independet Safety Data Monitoring board member: Immatics. N. Mederos Alfonso: Non-Financial Interests, Institutional, Advisory Board: Merck. D. Karp: Non-Financial Interests, Institutional, Advisory Board, Scientific Advisory Board: Promontory Therapeutics Inc.; Non-Financial Interests, Institutional, Principal Investigator: Promontory Therapeutics Inc. . D.R. Camidge: Financial Interests, Institutional, Advisory Board: AbbVie, Anheart, EMD Serono, Elevation, Hummingbird, Janssen, Medtronic , Mirati, Nalo Therapeutics, Onkure, Regeneron, Roche, Sanofi, Takeda, Theseus, Xcovery, Amgen, Blueprint, Mersana, Ribon, Roche/Genentech, Seattle Genetics, Turning Point, AstraZeneca, BMS, Eisai, Eli Lilly, GSK, Helssin, Pfizer, Qilu; Financial Interests, Institutional, Other, Safety Review Committee: Appolomics, Elevation; Financial Interests, Institutional, Other, Interstitial Lung Disease adjudication committee: AstraZeneca/Daiichi , Mersana , Daiichi Sankyo; Financial Interests, Institutional, Other, Data Safety Monitoring Board: Beigene Dizal , Hengrui, Bio-Thera, Helsinn; Financial Interests, Institutional, Other, Safety Review Committee/Steering Committee: AstraZeneca; Financial Interests, Institutional, Other, Data Safety Monitoring Committee: Beigene , Hengrui; Financial Interests, Institutional, Other, Data Safety Monitoring Board and NCCN: Eli Lilly; Financial Interests, Institutional, Advisory Board, Scientific Advisory Board: Kestrel, Nuvalent, Anchiarno; Financial Interests, Institutional, Stocks/Shares: Kestrel; Financial Interests, Institutional, Other, NCCN: Puma; Financial Interests, Institutional, Funding, Research funding: Inivata; Financial Interests, Institutional, Principal Investigator: AbbVie, AstraZeneca, Blueprint, Dizal, Inhibrx, Karyopharm, Nuvalent, Pfizer, Phosplatin (now Promontory), Psioxus, Rain, Roche/Genentech, Seattle Genetics, Takeda, Turning Point, Verastem. A.S. Mansfield: Financial Interests, Institutional, Other, Expert Think Tank: TRIPTYCH Health Partners; Financial Interests, Institutional, Other, Steering Committee: Janssen, Johnson & Johnson Global Services; Financial Interests, Institutional, Invited Speaker: BeiGene, Chugai Pharmaceutical (Roche); Financial Interests, Personal, Invited Speaker, CME Presentation: Antoni van Leeuwenhoek Kanker Instituut, University of Miami International Mesothelioma Symposium; Financial Interests, Institutional, Invited Speaker, CME Presentation: AXIS Medical Education, Intellisphere Llc, Answers in CME; Financial Interests, Institutional, Other, Travel Support: Roche; Financial Interests, Institutional, Advisory Board: AbbVie, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Takeda; Financial Interests, Institutional, Other, Study funding, article processing charges: Bristol Myers Squibb; Financial Interests, Institutional, Other, Grant Reviewer: Rising Tide; Financial Interests, Institutional, Other, Moderator: Ideology Health; Financial Interests, Institutional, Research Grant: Novartis, Verily; Non-Financial Interests, Personal, Invited Speaker, Non-remunerated Director: Mesothelioma Applied Research Foundation. C.Y. Yim: Financial Interests, Institutional, Stocks/Shares: Promontory Therapeutics Inc. T.D. Ames: Financial Interests, Institutional, Stocks/Shares: Promontory Therapeutics Inc. M. Price: Financial Interests, Institutional, Stocks/Shares: Promontory Therapeutics Inc. J. Baeck: Financial Interests, Institutional, Stocks/Shares: Promontory Therapeutics Inc. J.F. O'Donnell: Financial Interests, Institutional, Stocks/Shares: Promontory Therapeutics Inc. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: Beigene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), IASLC, ASCO, AACR; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. All other authors have declared no conflicts of interest.