1290TiP - A phase II multicenter, open label, non-randomized study of neoadjuvant and adjuvant treatment with IPH5201 and durvalumab in patients with resectable, early-stage (II to IIIA) non-small cell lung cancer (MATISSE)

Background

Adjuvant (adj) or neoadjuvant (neoadj) immunotherapy has been recently approved for the treatment of resectable early stage Non-Small Cell Lung Cancer (NSCLC), and further advances are needed. The combination of neoadj Durvalumab (D), an anti-PD-L1, combined with chemotherapy (CT) and adj D (AEGEAN) in early-stage NSCLC has recently demonstrated promising safety and efficacy. CD39 is an extracellular ectonucleotidase highly expressed in the tumor microenvironment (TME) that, sequentially with CD73, contributes to the production of adenosine (Ado), via hydrolysis of Ado triphosphate (ATP). IPH5201 is a blocking anti-CD39 monoclonal antibody that may promote antitumor immunity by accumulating immunostimulatory ATP released by CT-treated tumor cells and reducing immunosuppressive Ado levels in the TME. Moreover, IPH5201 improved the efficacy of CT+D in preclinical models. In a phase 1, IPH5201 + D was well tolerated and pharmacodynamically active.

Trial design

MATISSE is a phase II multicenter (France, Poland, Greece, Hungary, USA), single arm study (NCT05742607) sponsored by Innate Pharma, evaluating IPH5201 + D + CT in treatment-naive pts with resectable (stage II to IIIA) NSCLC. Up to 70 pts will receive neoadj IPH5201 + D in addition to platinum-doublet CT for 4 cycles followed by surgery within 40 days. Pts will thereafter receive adj IPH5201+D every 4 weeks for up to 12 cycles post-surgery or until recurrence or unacceptable toxicity. The primary objectives are to assess antitumor activity of neoadj treatment based on pathological complete response (pCR) and safety. The secondary objectives are to assess efficacy in terms of event free survival, disease free survival, feasibility of receiving the planned surgery, major pathological response, objective response rate, overall survival, pharmacokinetics and immunogenicity. Assessment of exploratory biomarkers is also planned. A Safety Review Committee will conduct evaluations on an ongoing basis and two interim analyses will be performed.

Clinical trial identification

IND:162253; NCT05742607; EudraCT: 2022-001903-42.

Editorial acknowledgement

Legal entity responsible for the study

Innate Pharma.

Funding

Innate Pharma.

Disclosure

F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda, AbbVie, Acea, Amgen, Eisai, Ignyta; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. O. Mercier: Financial Interests, Personal, Advisory Board, Board on surgical oncology (lung cancer): AstraZeneca; Financial Interests, Personal, Advisory Board, Board for CTEPH (non cancer related): MSD; Financial Interests, Institutional, Funding, Paceport Study investigator (non cancer related) Study on pulmonary hemodynamics: Edwards Lifesciences. A. Łowczak, S. Mandziuk, J. Kuzdzal, A. Dasgupta: Non-Financial Interests, Institutional, Principal Investigator: Innate. A. Koutras: Financial Interests, Personal, Advisory Board: Pierre Fabre, AstraZeneca, Gilead, Pfizer, Genesis, MSD, BMS; Financial Interests, Personal, Invited Speaker: Sanofi, Gilead; Financial Interests, Personal, Other, Travel, Accommodations: Rafarm, Lilly, Ipsen, Gilead, Pfizer; Financial Interests, Institutional, Funding: Lilly, Pfizer, Merck; Financial Interests, Institutional, Research Grant: AstraZeneca, Pierre Fabre, BMS, Demo, Faran, Amgen, Roche, Ipsen, Galenica, Win Medica. A.J. Leyco, P. Andre, C.L. Paturel, A. Boyer Chammard: Financial Interests, Institutional, Full or part-time Employment: Innate. R. Mager, P.G. Fraenkel: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca.