a study of ds-6000a in subjects with advanced renal cell carcinoma and ovarian tumors

Conditions: Renal Cell Carcinoma; Ovarian Tumor

Summary: 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 adverse events of r-dxd, and evaluate the effectiveness of r-dxd.

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.

Eligibility criteria:
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

Keywords: renal cell carcinoma ovarian tumor raludotatug deruxtecan (r-dxd; ds-6000a)