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

Phase 1Active Not RecruitingNCT04707248

Daiichi Sankyo179 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

179

Conditions

Renal Cell Carcinoma Ovarian Tumor

Interventions

DS-6000aDRUG

Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1

DS-6000aDRUG

Intravenous administration at RDE on Day 1 of Cycle 1

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

Arizona Oncology Associates, PC HOPE (A)A HOPE)

Tucson, Arizona, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

Florida Cancer Lake Mary

Lake Mary, Florida, United States

Outcomes

Primary Outcomes

Number of Participants With Dose-limiting toxicities (DLTs)

Time frame: Day 1 to Day 21 in Cycle 1 (each cycle is 21 days)

Number of Participants Reporting Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest

Time frame: From start of treatment up to 40 days after last dose, up to approximately 52 months

Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Dose Expansion)

ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR).

Time frame: From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 52 months (each cycle is 21 days)

Secondary Outcomes

Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve from Time Zero to 21 Days (AUC 21d) for R-DXd and its Metabolites

Time frame: Cycles 1 and 3, Day 1: Predose, 3 hours, 5 hours, 8 hours postdose, end of infusion (EOI); Cycles 1 and 3, Day 2; Cycles 1 and 3, Days 4, 8, and 15; Cycle 2, Day 1: predose and EOI; Cycle 4, Day 1 and every then 2 cycles: predose (each cycle is 21 days)

Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time (AUClast) for R-DXd and its Metabolites

Pharmacokinetic Analysis Maximum Plasma Concentration (Cmax) for R-DXd and its Metabolites

Time frame: Cycles 1 and 3, Day 1: Predose, 3 hours, 5 hours, 8 hours postdose, end of infusion (EOI); Cycles 1 and 3, Day 2; Cycles 1 and 3, Days 4, 8, and 15; Cycle 2, Day 1: predose and EOI; Cycle 4, Day 1 and then every 2 cycles: predose (each cycle is 21 days)

Data from ClinicalTrials.gov

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