Daiichi Sankyo Initiates First-in-Human Trial of DS3790, Novel CD37-Targeted ADC for B-Cell Lymphoma
核心洞察
Daiichi Sankyo has dosed the first patient in a phase 1/2 trial evaluating DS3790 (搜索), a potential first-in-class CD37 (搜索)-directed antibody drug conjugate for relapsed or refractory B-cell non-Hodgkin lymphoma (搜索).
DS3790 (搜索) represents the company's first DXd ADC in hematology, targeting CD37 (搜索), a transmembrane protein overexpressed on malignant B-cells with no currently approved therapies.
The multicenter trial will enroll approximately 420 patients globally to assess safety and efficacy, with plans to evaluate both monotherapy and combination approaches.
Daiichi Sankyo has achieved a significant milestone in hematologic oncology by dosing the first patient in a phase 1/2 trial of DS3790 (搜索), a potential first-in-class CD37 (搜索)-directed antibody drug conjugate (ADC) for patients with relapsed or refractory B-cell non-Hodgkin lymphoma (搜索). This marks the company's inaugural entry into hematology with its proprietary DXd ADC technology platform.
"The initiation of this trial of DS3790 (搜索) with its novel CD37 (搜索) target marks a significant milestone as our first DXd antibody drug conjugate in hematology," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "DS3790 expands our portfolio to seven DXd antibody drug conjugates, all developed using our in-house technology, underscoring our dedication to scientific innovation to create new medicines for patients with cancer."
Novel Target Addresses Unmet Medical Need
CD37 (搜索) is a transmembrane protein that plays a role in regulating cell survival and is overexpressed on malignant B-cells, making it a promising therapeutic target. Currently, there are no CD37-directed therapies approved for any type of cancer, highlighting the potential significance of DS3790 (搜索)'s development.
B-cells are a type of white blood cell that help the body fight infection but can uncontrollably multiply and fail to function properly in malignancies. Because of CD37 (搜索)'s high prevalence on B-cells, it is considered a promising therapeutic target for the treatment of B-cell cancers.
The medical need is substantial, with more than 604,000 cases of non-Hodgkin lymphoma (搜索) diagnosed in 2021, resulting in approximately 267,000 deaths globally. B-cell non-Hodgkin lymphoma (搜索) accounts for more than 85% of all non-Hodgkin lymphoma cases with a five-year survival rate of 74%. While advances in targeted therapies have improved outcomes in B-cell non-Hodgkin lymphoma, many patients with relapsed or refractory disease continue to face limited treatment durability and poor long-term survival.
Comprehensive Phase 1/2 Trial Design
The multicenter, open-label, multi-cohort, first-in-human phase 1/2 trial will assess the safety and efficacy of DS3790 (搜索) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (搜索). The study is designed in two distinct phases to optimize dosing and evaluate therapeutic potential.
The first part of the trial focuses on dose escalation, evaluating DS3790 (搜索) as a monotherapy to determine the recommended dose for expansion. The second part consists of multiple expansion cohorts to further evaluate DS3790 as a monotherapy. Following the assessment of preliminary safety and efficacy in the monotherapy portion, subsequent cohorts will evaluate DS3790 in combination with other targeted therapies in both dose escalation and dose expansion phases.
The trial will evaluate comprehensive safety endpoints including dose-limiting toxicities and adverse events, as well as efficacy endpoints including overall response, disease control rate, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetics and biomarker endpoints will also be assessed.
The study is expected to enroll approximately 420 patients across multiple sites globally, including Asia, Europe and North America.
Advanced ADC Technology Platform
DS3790 (搜索) is designed using Daiichi Sankyo's proprietary DXd ADC technology and is comprised of a humanized anti-CD37 (搜索) IgG1 monoclonal antibody attached to a number of topoisomerase I (搜索) inhibitor payloads (exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development, each comprised of a monoclonal antibody attached to topoisomerase I (搜索) inhibitor payloads via tetrapeptide-based cleavable linkers. The DXd ADCs include ENHERTU and DATROWAY, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc. DS-3939 and DS3790 (搜索) are being developed by Daiichi Sankyo.
The broader Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical development crafted from ADC technology discovered in-house by the company. An additional ADC being developed is DS3610 (搜索), which consists of an antibody attached to a novel payload that acts as an agonist of STING (搜索).
All investigational medicines in development, including DS3790 (搜索), have not been approved for any indication in any country, and safety and efficacy have not been established.