Abstract 199TiP
Background
CD73 is an extracellular ectonucleotidase overexpressed in the tumor microenvironment (TME) of multiple cancers. Extracellular adenosine triphosphate (ATP) released by necrotic cells is hydrolyzed into adenosine monophosphate (AMP), which is subsequently degraded by CD73 into immunosuppressive adenosine. CD73 overexpression has been associated with poor prognosis, conferring resistance to chemotherapy and anti-HER2 therapy. IPH5301 is a humanized IgG1 monoclonal antibody (mAb) with a functionally silent Fc domain, specifically inhibiting both soluble and membrane CD73 enzymatic activity, and restoring proliferation of immune T cells more effectively than other anti-CD73 mAbs in clinical development. IPH5301 has the potential to release TME from adenosine-mediated immune suppression, thereby leading to increased anti-tumor immunity.
Trial Design
CHANCES is a first-in-human, open label, European, multi cohort phase I study (NCT05143970). The dose escalation cohort will evaluate 4 dose levels of IPH5301 administered alone IV every 2 weeks until progression or toxicity. The escalation will be guided by an adaptive Bayesian model, enrolling cohorts of 2 to 3 patients with advanced and/or metastatic cancer. A maximum of 15 patients is planned. In the expansion cohort, IPH5301 will be administered at the recommended dose (RP2D) and the next lower dose (RP2D-1) in combination with trastuzumab and paclitaxel in 12 patients with advanced/metastatic HER2-positive breast and gastric/esogastric cancer. The primary objectives are to evaluate the safety profile, to determine the maximum tolerated dose (MTD) of IPH5301 alone in advanced /metastatic tumors (dose-escalation part) and to recommend a dose of IPH5301 to be combined with paclitaxel and trastuzumab in patients with advanced/metastatic HER2-positive breast and gastric/esogastric cancer (expansion part). The secondary objectives are to evaluate pharmacokinetic, immunogenicity and to assess preliminary clinical activity. Finally, exploratory objectives include pharmacodynamics such as CD73 expression, occupancy and enzymatic activity.
Clinical trial identification
NCT05143970 Initial release 11/17/2021.
Legal entity responsible for the study
Paoli Calmettes Institute.
Funding
Innate-Pharma.
Disclosure
A. Gonçalves: Non-Financial Interests, Personal and Institutional, Project Lead: Paoli Calmettes Institute. N. Kotecki: Non-Financial Interests, Personal and Institutional, Advisory Board: Innate-Pharma. D.B. Marie: Financial Interests, Personal, Full or part-time Employment: Innate Pharma. 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. P. André: Financial Interests, Personal, Full or part-time Employment: Innate-Pharma. All other authors have declared no conflicts of interest.