Ovarian Tumor, Renal Cell Carcinoma
Conditions
Keywords
Renal Cell Carcinoma, Ovarian Tumor, Raludotatug deruxtecan (R-DXd; DS-6000a)
Brief 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.
Detailed 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.
Interventions
DRUGDS-6000a
Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1
Sponsors
Daiichi Sankyo
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Dose Expansion) | From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 52 months (each cycle is 21 days) | ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR). |
| Number of Participants With Dose-limiting toxicities (DLTs) | 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 | From start of treatment up to 40 days after last dose, up to approximately 52 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Analysis Lowest Plasma Concentration (Ctrough) for R-DXd and its Metabolites | 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) | — |
| Pharmacokinetic Analysis Time to Maximum Plasma Concentration (Tmax) for R-DXd and its Metabolites | 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) | — |
| Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Per Investigator and Blinded Independent Central Review (Dose Escalation) | From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 52 months (each cycle is 21 days) | ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR). |
| Duration of Response (DoR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review | From date of first documented response to date of progression or death due to any cause (whichever occurs first), up to approximately 52 months | DoR is defined as the duration from the first documented response to the date of progression or death due to any cause. |
| Disease Control Rate (DCR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review | From start of treatment up to first documented response (CR, PR, or SD), disease progression, or death (due to any cause), up to approximately 52 months | DCR is defined as the proportion of participants with BOR of CR, PR, or SD. |
| Clinical Benefit Rate (CBR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review | From date of first documented response (CR, PR) whichever occurs first or SD lasting at least 180 days to disease progression or death (due to any cause), up to approximately 52 months | CBR is defined as the proportion of participants with BOR of CR or PR, or participants with stable disease (SD) lasting at least 180 days. |
| Time to Response (TTR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review | From start of treatment up to first documented response (CR, PR, or SD), disease progression, or death (due to any cause), up to approximately 52 months | — |
| Progression-free Survival Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review | From start of treatment up to disease progression or death (due to any cause), up to approximately 52 months | — |
| Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve from Time Zero to 21 Days (AUC 21d) for R-DXd and its Metabolites | 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) | — |
| Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Percentage of Participants Who Have Treatment-emergent ADA | Cycle 1 Day 1, Cycle 1 Day 15, and pre-dose on Day 1 of Cycle 2 through Cycle 4; then every 2 cycles from Cycle 4 through the end of treatment visit (each cycle is 21 days), and 40-day safety follow up visit, up to approximately 52 months | — |
| Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time (AUClast) for R-DXd and its Metabolites | 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 Maximum Plasma Concentration (Cmax) for R-DXd and its Metabolites | 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) | — |
Countries
Japan, United States
Contacts
STUDY_DIRECTORGlobal Clinical Leader
Daiichi Sankyo
Outcome results
None listed