A First-in-Human Trial of DS3790a in Participants With Hematological Malignancies

Summary: This clinical trial is designed to assess the safety, preliminary efficacy, and pharmacokinetics (PK) of DS3790a monotherapy and combination regimens in participants with hematological malignancies.
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Short title: A First-in-Human Trial of DS3790a in Participants With Hematological Malignancies
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Official title: A Phase 1/2, Multicenter, Open-Label, Multi-Cohort, First-in Human Trial of DS3790a, a DXd-ADC Targeting CD37, for Hematological Malignancies
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Control arm: Active comparator
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Registry reports results: No
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Listing at source: Listed
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Recruitment status: Recruiting
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Phase: Phase 1/Phase 2
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Study type: Interventional
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Completion date: 2030-11-30
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First posted: 2025-10-24
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Registry last updated: 2026-08-24
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Primary completion date: 2030-11-30
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Start date: 2026-01-16
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Participants: 420
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Participant count basis: Estimated
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Planned participants: 420
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Protocol amendments: 1
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Number of sites: 8
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Data monitoring committee: No
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Registry sponsor category: Industry
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Lead sponsor: Daiichi Sankyo
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Source registry: ClinicalTrials.gov
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Registry ID: NCT07220616
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ClinicalTrials.gov ID: NCT07220616
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Registry record: Open registry record
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Allocation: Randomised
Model: Sequential
Purpose: Treatment
Masking: No masking

Sources for study design

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Number of Participants Reporting Dose-limiting Toxicities, Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events of Special Interest, and Deaths in Participants With Hematological Malignancies
Timeframe: Baseline up to 5 years
Adverse events (AEs) will be graded using NCI-CTCAE version 5.0.
Complete Response in Participants With Hematological Malignancies by Blinded Independent Central Review (Cohort A Randomization Optimization Phase, Cohort A Phase 2)
Timeframe: Baseline up to 5 years
Complete Response (CR) is defined as participants with CR as measured by BICR assessment.
Complete Response in Participants With Hematological Malignancies by Investigator Assessment (Cohort B Randomization Optimization Phase)
Timeframe: Baseline up to 5 years
Complete Response (CR) is defined as participants with CR as measured by investigator assessment.

Objective Response by Investigator Assessment In Participants With Hematological Malignancies
Timeframe: Baseline up to 5 years
Objective response (OR) is defined as participants with complete response (CR) or partial response (PR) as measured by investigator assessment.
Complete Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)
Timeframe: Baseline up to 5 years
Complete response (CR) is defined as participants with CR as best overall response (BOR) as measured by investigator assessment.
Disease Control in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)
Timeframe: Baseline up to 5 years
Disease control (DC) is defined as participants with CR, PR or stable disease as BOR as measured by investigator assessment.
Duration of Complete Response and Duration of Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)
Timeframe: Baseline up to 5 years
Duration of Complete Response (DoCR) is defined as the time from the date of first documentation of CR to the first documentation of objective tumor progression by investigator assessment or to death due to any cause, whichever occurs first. DoCR will be calculated for responders (CR) only. Duration of Response (DoR) is defined as the time from the date of first documentation of objective response (CR or PR) to the first documentation of objective tumor progression by investigator assessment or to death due to any cause, whichever occurs first. DoR will be calculated for responders (CR or PR) only.
Time to Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)
Timeframe: Baseline up to 5 years
Time to Response (TTR) is defined as the time from the date of the start of trial intervention or randomization if randomized, to the date of the first documentation of objective response (CR or PR) by investigator assessment. TTR will be calculated for responders (CR or PR) only.
Progression-free Survival Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)
Timeframe: Baseline up to 5 years
Progression-free Survival (PFS) is defined as time from the date of the start of trial intervention or randomization if randomized, to the date of radiographic disease progression, defined as the first documented objective PD by investigator assessment or death due to any cause.
Overall Survival Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)
Timeframe: Baseline up to 5 years
Overall Survival (OS) is defined as the time from the date of the start of trial intervention or randomization if randomized, to the date of death due to any cause.

Sources for outcomes

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Sex: All
Age groups: Adults, Older adults
Minimum age: 18 Years
Healthy volunteers: No

To be eligible to participate in this trial, an individual must meet all the following criteria:

Sign and date the ICF, prior to the start of any trial-specific procedures.
Adults >=18 years at the time the ICF is signed.
History of one of the histologically documented hematologic malignancies according to the 5th edition of WHO classification as specified in the protocol.
NHL participants only: Agree to provide baseline tumor tissue samples as specified in the protocol.
ECOG PS of 0, 1 or 2 assessed no more than 14 days prior to initiation of trial intervention.
Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to initiation of trial intervention as specified in the protocol.
Has an LVEF >=50% by either an ECHO or MUGA within 28 days before the trial starts.
Life expectancy of at least 3 months.
Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other trial procedures, and trial restrictions.
A woman of childbearing potential is eligible to participate if she meets all criteria as specified in the protocol.
A male participant capable of producing sperm is eligible to participate if he agrees to all criteria as specified in the protocol.

An individual who meets any of the following criteria will be excluded from participating in this trial:

Prior Allo-SCT.
Prior solid organ transplantation.
Inadequate washout period before initiation of trial intervention as specified in the protocol.
Evidence of brain or leptomeningeal disease (spinal cord or CNS metastases) based on history and physical examination, unless treated and with radiologically documented lack of progression within 4 weeks prior to initiation of trial intervention.
Uncontrolled or significant cardiovascular disease as specified in the protocol.
Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder and any autoimmune, connective tissue, or inflammatory disorder with potential pulmonary involvement, or prior pneumonectomy.
Has been diagnosed with another malignancy within the previous 3 years.
Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia and lymphocytopenia) not yet resolved to NCI-CTCAE Version 5.0, Grade <=1 or baseline.
Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
Has active or uncontrolled HBV, HCV, or HIV infections.