Daiichi Sankyo Begins Phase 1/2 Human Trials Of Lymphoma Drug DS3790
Daiichi Sankyo has initiated clinical development of DS3790, marking the first dosing of a patient in a first-in-human Phase 1/2 trial evaluating the investigational therapy in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
DS3790 is a potential first-in-class CD37-directed DXd antibody-drug conjugate (ADC) discovered and developed by Daiichi Sankyo. It is the company’s first DXd ADC to enter clinical development in hematology, expanding its in-house ADC portfolio.
The multicenter, open-label, multi-cohort Phase 1/2 study will assess the safety, tolerability, pharmacokinetics, biomarkers, and preliminary efficacy of DS3790. The trial will begin with a dose-escalation phase evaluating DS3790 as a monotherapy to determine the recommended dose for expansion, followed by multiple dose-expansion cohortscontinuing monotherapy evaluation. Subsequent cohorts will assess DS3790 in combination with other targeted therapies during both dose-escalation and dose-expansion phases.
Safety endpoints include dose-limiting toxicities and adverse events, while efficacy endpoints include overall response rate, disease control rate, duration of response, time to response, progression-free survival, and overall survival. The study is expected to enroll approximately 420 patients globally, with trial sites across Asia, Europe, and North America.
CD37 is a transmembrane protein involved in regulating cell survival and is highly expressed on malignant B-cells, making it a promising therapeutic target. Currently, no CD37-directed therapies are approved for any cancer indication.
B-cell non-Hodgkin lymphoma accounts for more than 85% of all non-Hodgkin lymphoma cases. Globally, more than 604,000 cases were diagnosed in 2021, with approximately 267,000 deaths. Despite advances in targeted therapies, patients with relapsed or refractory disease continue to face limited treatment durability and poor long-term outcomes.
DS3790 is engineered using Daiichi Sankyo’s proprietary DXd ADC technology, combining a humanized anti-CD37 IgG1 monoclonal antibody with a topoisomerase I inhibitor payload (exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
The company’s ADC portfolio currently includes eight ADCs in clinical development, all derived from in-house technology. The DXd ADC platform comprises seven ADCs, including ENHERTU® and DATROWAY®, which are jointly developed and commercialized with AstraZeneca, as well as ifinatamab deruxtecan, raludotatug deruxtecan, and patritumab deruxtecan, which are jointly developed with Merck & Co. DS3790 and DS-3939 are being developed solely by Daiichi Sankyo. An additional ADC, DS3610, incorporates a novel payload designed to act as a STING agonist.
The initiation of this trial underscores Daiichi Sankyo’s continued focus on expanding its oncology pipeline through targeted ADC innovation, particularly in areas of high unmet need within hematologic malignancies.
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