Abstract 188P
Background
IPH5201 is an anti-CD39 monoclonal antibody that may promote antitumour immunity by increasing immunostimulatory ATP and reducing immunosuppressive adenosine levels in the tumour microenvironment. This first-in-human, multicentre, non-randomised, open-label, phase 1 study (NCT04261075) assessed the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of IPH5201 in patients (pts) with advanced solid tumours.
Methods
The study consisted of 2 dose-escalation parts: ascending doses of IPH5201 (100, 300, 1000 and 3000 mg) IV Q3W, and ascending doses of IPH5201 + D 1500 mg IV Q3W. Primary endpoints were safety and tolerability; key secondary endpoints were preliminary efficacy and PK. Biomarkers were assessed as exploratory endpoints.
Results
Overall, 57 pts received treatment (IPH5201, n=38; IPH5201 + D, n=19). Median age was 62 years (range, 41–78); 54.4% were male. Pts had a median of 3 prior therapies (range, 2–11). As of 7 Jul 2022, all pts had discontinued treatment, 89.5% due to disease progression. Treatment-emergent adverse events (AEs) occurred in 96.5% of pts. Treatment-related AEs (TRAEs) occurred in 66.7% of pts (37/57 [64.9%] related to IPH5201; 11/19 [57.9%] related to D); 10.5% had grade 3 TRAEs, with no grade 4 or 5 TRAEs. The most common TRAEs were infusion-related reactions (21.1%), fatigue (17.5%), and nausea, arthralgia, tumour pain and pruritus (each 8.8%). Median duration of exposure to IPH5201 was 9.3 wks (range, 3.0–66.1) and to D was 8.7 wks (range, 3.0–66.1). 22/57 pts (38.6%) had stable disease; there were no partial or complete responses. Median progression-free survival was 1.4 mo (range, 0–15.2); median overall survival was 8.2 mo (range, 1.0–22.1). IPH5201 saturated soluble CD39 at ≥300 mg and CD39 on immune cells at 3000 mg and decreased tumoural enzymatic activity in 5/8 pts. IPH5201 PK were non-linear at ≤300 mg and linear at ≥1000 mg. An indirect response PD model describing the relationship between IPH5201 concentration and free membrane CD39 on monocytes proposed 3000 mg Q3W or Q4W as the recommended phase 2 dose.
Conclusions
IPH5201 was well tolerated when used alone or in combination with D, with no new safety signals identified. PD were consistent with the mechanism of action.
Clinical trial identification
NCT04261075.
Editorial acknowledgement
Medical writing support for this abstract, under the direction of the authors, was provided by Werner Gerber of Ashfield MedComms (Kimberley, South Africa), an Inizio company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M. Imbimbo: Financial Interests, Personal, Advisory Board: Immatics Therapeutics; Financial Interests, Institutional, Principal Investigator: BMS, T3P Therapeutics, AstraZeneca. A. Hollebecque: Financial Interests, Institutional, Research Grant: Incyte; Non-Financial Interests, Personal, Principal Investigator: Sanofi, Celgene, BMS, Lilly, Mirati, Seattle Genetics, AbbVie, Pfizer, AstraZeneca, Gilead, Merus; Financial Interests, Personal, Advisory Role: Amgen, BMS, Basilea, Incyte, Servier, Relay Therapeutics, Taiho, QED Therapeutics. A. Italiano: Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer, BMS, MSD, Merck, Novartis, Parthenon, PharmaMar. M. McKean: Financial Interests, Institutional, Principal Investigator: Aadi Biosciences, Accutar Biotechnology, Alpine Immune Sciences, Arcus Biosciences, Arvinas, Ascentage Pharma Group, Astellas, Bayer, Bicycle Therapeutics, BioMed Valley Discoveries, BioNTech, Dragonfly therapeutics, EMD Serono, Epizyme, Erasca, Exelixis, Foghorn Therapeutics, G1 Therapeutics, Genentech, Gilead, GSK, IDEAYA Biosciences, Ikena Oncology, ImmVira Pharma, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, AstraZeneca, Mereo BioPharma, Metabomed, Moderna, NBE Therapeutics, Nektar, Novartis, OncoC4, Oncorus, PACT Pharma, Pfizer, Plexxikon, Poseida, Prelude Therapeutics, Pyramid Biosciences, Regeneron, Sapience Therapeutics, Scholar Rock, Seattle Genetics, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, TopAlliance Biosciences, Xilio; Financial Interests, Institutional, Other, Consulting: Astellas Pharma, AstraZeneca, BicycleTX Limited, Castle Biosciences, Eisai, IDEAYA Biosciences, iTeos, Moderna, Pfizer. T. Macarulla: Financial Interests, Personal, Other, Travel: Servier, AstraZeneca, Sanofi, Incyte; Financial Interests, Personal, Other, Consultancy: Swedish Orpahn Biovitrum AB, Ability Pharmaceuticals SL, AstraZeneca, Basilea Pharma, Baxter, BioLineRX Ltd, Celgene, Eisai, Incyte, Ipsen Bioscience, Eli Lilly, Marketing Farmacéutico & Investigación Clínica, S.L, MDS, Novocure, QED Therapeutics, Roche, Sanofi-Aventis, Servier, Zymeworks. E. Castanon Alvarez: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Roche, Beigene; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, BMS, Roche, Merck, MSD; Financial Interests, Personal, Training: BMS. B.A. Carneiro: Financial Interests, Institutional, Research Grant: AstraZeneca, AbbVie, Actuate Therapeutics, Astellas, Bayer, Dragonfly Therapeutics, Pfizer, Repare Therapeutics; Financial Interests, Personal, Advisory Board: Foundation Medicine, Seattle Genetics. R. Mager: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. V. Barnhart: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. E. Murtomaki: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Y. He: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. Z.A. Cooper: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. E. Tu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Linke: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. C. Fan: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. D. Zhao: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Boyer Chammard: Financial Interests, Personal, Full or part-time Employment: Innate Pharma. C.L. Paturel: Financial Interests, Personal, Full or part-time Employment: Innate Pharma; Financial Interests, Personal, Stocks/Shares: Innate Pharma. P.G. Fraenkel: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Powderly: Financial Interests, Personal, Other, Consulting: Aavocyte, Boxer Capital; Financial Interests, Personal, Ownership Interest, Founder and Owner: BioCytics Inc; Financial Interests, Personal, Ownership Interest, Founder: Carolina BioOncology; Non-Financial Interests, Personal and Institutional, Principal Investigator: AbbVie, Adagene, Alkermes, Apros, Arcus Biosciences, AstraZeneca, Atreca, BJ BioScience, BMS, Calico Life Sciences, Conjunpro BioTherapeutics, Cullinan, EMD Serono, Fate Therapeutics, FLX Bio, Genentech/Roche, I-MAB Pharma, Immune-Onc, Incyte, Jounce Therapeutics, Macrogenics, Molecular Templates, NexCure, Nuvation, Repertoire Immune Medicine, Seattle Genetics, Sequenom, Tempest Therapeutics, Top Alliance BioScience, Trethera, Xilio, Zenshine Pharma; Non-Financial Interests, Institutional, Research Grant: Merck, MT Group, Precision for Medicine, Replimmune, STEMCELL Technologies, Xilis; Financial Interests, Personal and Institutional, Research Grant: PIOMA.