A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors

Daiichi Sankyo

Status and phase: Enrolling; Phase 1

Conditions: Ovarian Tumor; Renal Cell Carcinoma

Treatments: Drug: DS-6000a

Study type: Interventional

Funder types: Industry

Identifiers

NCT04707248

DS6000-A-U101

Details and patient eligibility

About

This clinical trial will evaluate raludotatug deruxtecan (R-DXd; DS-6000a) in participants with advanced renal cell carcinoma (RCC) and ovarian cancer (OVC). The main goals of this study will be to investigate the recommended dose of R-DXd that can be given safely to participants, assess the side effects of R-DXd, and evaluate the effectiveness of R-DXd.

Full description

R-DXd is an antibody drug conjugate that specifically binds to CDH6 on the cell surface of target cells, which leads to the internalization of R-DXd into the cells. MAAA-1181a that is released from R-DXd in the target cells inhibits cell replication and induces cell apoptosis.

This study will evaluate R-DXd given as a single agent once every 21 days. The dose escalation phase will enroll participants with OVC and RCC, and is designed to assess the safety and tolerability of R-DXd and to determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE). Following the selection of the RDE, the dose expansion phase will be initiated to evaluate clinical activity of R-DXd.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent
• At least 18 years of age
• Eastern Cooperative Oncology Group Performance Status score of 0 or 1
• Availability of archived tumor tissue samples
• Has a left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before start of study treatment
• Has adequate organ function within 7 days before the start of study treatment
• Has an adequate treatment washout period prior to start of study treatment
• Male participants with female partners of childbearing potential and female participants of child-bearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4 months (for males) and for at least 7 months (for females) after the last dose of study drug.

Exclusion criteria

• Has had prior treatment with other CDH6-targeted agents
• Has had prior treatment with an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan, datopotamab deruxtecan, ifinatamab deruxtecan, DS-3939)
• Has history or current presence of CNS metastases except for participants who have completed radiotherapy or surgery ≥2 weeks before the start of study treatment and have no evidence of disease progression in the CNS and no requirement for chronic corticosteroid therapy within 2 weeks before the start of study treatment
• Has multiple primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years)
• Has a history of myocardial infarction or unstable angina within 6 months before start of study treatment
• Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or a cardiac arrhythmia requiring treatment
• Lung-specific intercurrent clinically significant illnesses
• Has an uncontrolled infection requiring systemic therapy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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180 participants in 3 patient groups

Dose Escalation

Experimental group

Description:

Participants with ovarian cancer (OVC) or renal cell carcinoma (RCC) will receive an intravenous infusion of R-DXd (starting dose 1.6 mg/kg).

Treatment:

Drug: DS-6000a

Drug: DS-6000a

Dose Expansion: Cohort B-1

Experimental group

Description:

Participants with RCC will receive an intravenous infusion of R-DXd at the RDE. Enrollment has ended for this cohort.

Treatment:

Drug: DS-6000a

Drug: DS-6000a

Dose Expansion: Cohort B-2

Experimental group

Description:

Participants with OVC will receive an intravenous infusion of R-DXd at the RDE.

Treatment:

Drug: DS-6000a

Drug: DS-6000a