682TiP - A phase I, first-in-human study of DS-1471 in patients with advanced/metastatic solid tumors

Background

CD147 is an immunoglobulin (Ig) superfamily membrane protein involved in key hallmarks of cancer such as cell survival, proliferation, and metastasis; it is highly expressed across a range of cancers. High CD147 expression in tumor tissue is associated with poor prognosis in multiple solid tumors, making CD147 an attractive target for novel cancer therapeutics. DS-1471, a humanized IgG4 monoclonal antibody targeting CD147, has shown preclinical antitumor activity by inhibiting complex formation between CD147 and diverse binding partners and inducing cancer cell apoptosis via upregulating a stress response. The toxicity profile and antitumor activity of DS-1471 in preclinical studies warrant clinical investigation. DS-1471 is currently being evaluated in a Phase 1 trial.

Trial design

DS-1471-079 (NCT06074705) is a Phase 1, first-in-human, open-label, multicenter, 2-part dose-escalation and -expansion study in adult patients with locally advanced or metastatic solid tumors who are unable to tolerate, whose tumors are refractory to, or who lack available standard treatment (N≈80). The study is currently recruiting. Patients must have ≥1 measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1, have an Eastern Cooperative Oncology Group performance status of 0 or 1, and consent to baseline (mandatory) and on-treatment (if not contraindicated) biopsy. During dose escalation, patients will receive DS-1471 intravenously (IV) on Day 1 of each 28-day cycle. The primary objective of dose escalation is to evaluate the safety and tolerability of DS-1471 IV and determine the maximum tolerated dose and/or recommended dose for expansion (RDE). The dose-expansion part will comprise tumor-specific cohorts, determined based on dose escalation and preclinical data, in which patients receive DS-1471 IV at the RDE. The primary objective of dose expansion is to evaluate the safety of DS-1471 IV at the RDE. Safety measures for primary outcomes in this study include dose-limiting toxicities and treatment-emergent adverse events. Secondary outcome measures for both parts include best overall response, time to response, duration of response, progression-free survival, and overall survival.

Clinical trial identification

NCT06074705.

Editorial acknowledgement

Medical writing support was provided by Alexandra Mascaro, PhD, of Boldscience®, Inc.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo.

Disclosure

S. Koganemaru: Financial Interests, Institutional, Principal Investigator: Amgen, Bristol Myers Squibb, Daiichi Sankyo, AbbVie, MSD, Incyte, Eisai Inc. N. Yoshizuka: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. S. Mizuno, S. Hirai: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. N. Yamamoto: Financial Interests, Personal, Advisory Role: Eisai, Takeda, Boehringer Ingelheim, Cmic, Chugai, Merck, Healios; Financial Interests, Personal, Invited Speaker: Chugai, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Principal Investigator: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, Ono, Janssen Pharma, MSD, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, Toray, Kaken, AstraZeneca, Cmic, InventisBio, Rakuten Medical.