A first-in-human (FIH) phase I study of IPH5301, an anti-CD73 monoclonal antibody (mAb), in patients with advanced solid tumors (AST) (CHANCES, NCT05143970)

BackgroundCD73 is an extracellular ectonucleotidase overexpressed in the tumor microenvironment of multiple cancers, involved in the production of the immunosuppressive adenosine and associated with poor prognosis and therapeutic resistance. IPH5301 is a humanized Fc-silent IgG1 mAb with a unique epitope, translating into superior CD73 blocking activity and restoration of T cell proliferation. CHANCES is a FIH phase I study evaluating IPH5301 in AST as single-agent in dose escalation and in combination with paclitaxel-trastuzumab.MethodsPatients with AST refractory to conventional therapies were eligible. IPH5301 was administered every 2 weeks until disease progression and 4 dose levels (DL) were investigated. Dose escalation was guided by an adaptive Bayesian model. Primary objective was to assess safety and tolerability. Dose-limiting toxicities (DLT) were evaluated during the first 4 weeks. Secondary objectives included evaluation of pharmacokinetics, immunogenicity and clinical activity. Results from single-agent dose escalation are reported.ResultsAs of Jan 2, 2024, 12 patients received IPH5301, including breast (n=8) and ovarian cancer (n=4). All patients had received prior chemotherapy. No DLT was observed across the 4 DL. The median number of administrations was 4 (1-43). No grade 3 or more drug-related adverse event (AE) was noted. Two patients had Gr. 2 infusion-related reactions. Other drug-related Aes were mild or moderate and included asthenia, nausea, abdominal pain, diarrhea, vomiting (≥2patients). One partial response was confirmed in ovarian cancer with duration of response superior to 9 months. Four stable diseases have been observed. IPH5301 exposure was maintained above target concentration from DL2. No immunogenicity was noted. Saturation of membrane and soluble CD73 in peripheral blood, as well as blockade of soluble CD73 enzymatic activity in sera were achieved from DL2.ConclusionsIPH5301, up to the highest tested dose, was safe and well-tolerated with preliminary signals of monotherapy antitumor activity. Combination of IPH5301 with paclitaxel-trastuzumab is currently explored in HER2-positive advanced breast and gastric cancer patients.Clinical trial identificationEudraCT 2021-002692-19; EU number 2023-504605-36-00.Legal entity responsible for the studyInstitut Paoli-Calmettes.FundingInnate Pharma.DisclosureA. Mailliez: Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, Novartis, Roche; Financial Interests, Personal, Invited Speaker: Menarini, Oseus, Seagen, Pfizer, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: GSK. C. Vicier: Financial Interests, Personal, Advisory Role: Owkin, Pfizer, Daiichi Sankyo, BMS; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Personal, Other, travel, accommodation, expenses: Astellas Pharma, Pfizer, Novartis; Financial Interests, Personal, Financially compensated role: Seagen; Financial Interests, Institutional, Research Funding: BMS. M. Guerin: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, Ipsen; Financial Interests, Personal, Other, travel, expenses: Bayer, MSD, Janssen Oncology, Pfizer, Ipsen. B. Chanez: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, AstraZeneca, Servier; Financial Interests, Personal, Leadership Role: Servier; Financial Interests, Personal, Other, travel, accommodation, expenses: Amgen, Pfizer, BMS, Servier; Financial Interests, Personal, Financially compensated role: BMS, Servier, Amgen; Financial Interests, Institutional, Research Funding: AstraZeneca/Medimmune. N. Kotecki: Financial Interests, Institutional, Research Funding: BMS GmbH & Co. KG; Financial Interests, Personal, Other, travel, expenses: Pfizer, Ose Pharma, Byondis. A. Widemann, S. Panzolato, A. Boyer Chammard, P. André, C.L. Paturel: Financial Interests, Personal, Full or part-time Employment: Innate Pharma. A.H. Awada: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Daiichi, Eisai, Genomic Health, Hengrui, Innate, Ipsen, Leo Pharma, Lilly, MSD, Menarini, Merck, Novartis, Pfizer, Seattle Genetics; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Daiichi, Eisai, Genomic Health, Ipsen, Leo Pharma, Lilly, MSD, Merck, Novartis, Pfizer, Seattle Genetics; Financial Interests, Institutional, Research Grant: BMS, Roche; Non-Financial Interests, Other, Co-chair: Oncodistinct network for clinical research; Non-Financial Interests, Other, Scientific committee member: Fondation contre le cancer (Belgium; Non-Financial Interests, Other, Member: BSMO; Non-Financial Interests, Other, Chair: AllCan Belgium. A. Gonçalves: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, MSD, Innate Pharma, Parexel, Gilead; Financial Interests, Institutional, Local PI: Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Roche, MSD; Other, travel: Mylan; Other, travel, accommodation, meeting registration: Mylan, Novartis, Roche, Menarini. All other authors have declared no conflicts of interest.