Description:
This clinical trial will evaluate 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 DS-6000a that can be given safely to participants, assess the side
effects of DS-6000a, and evaluate the effectiveness of DS-6000a.
Title
- Brief Title: A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors
- Official Title: Phase I, Two-Part, Multi-Center, First-in-Human Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors
Clinical Trial IDs
- ORG STUDY ID:
DS6000-A-U101
- NCT ID:
NCT04707248
Conditions
- Renal Cell Carcinoma
- Ovarian Tumor
Interventions
Drug | Synonyms | Arms |
---|
DS-6000a | | Dose Escalation |
DS-6000a | | Dose Expansion: Cohort B-1 |
Purpose
This clinical trial will evaluate 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 DS-6000a that can be given safely to participants, assess the side
effects of DS-6000a, and evaluate the effectiveness of DS-6000a.
Detailed Description
DS-6000a is an antibody drug conjugate that specifically binds to CDH6 on the cell surface of
target cells, which leads to the internalization of DS-6000a into the cells. MAAA-1181a that
is released from DS-6000a in the target cells inhibits cell replication and induces cell
apoptosis.
This study will evaluate DS-6000a 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 DS-6000a 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 DS-6000a.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Escalation | Experimental | Participants with ovarian cancer (OVC) or renal cell carcinoma (RCC) will receive an intravenous infusion of DS-6000a (starting dose 1.6 mg/kg). | |
Dose Expansion: Cohort B-1 | Experimental | Participants with RCC will receive an intravenous infusion of DS-6000a at the RDE. | |
Dose Expansion: Cohort B-2 | Experimental | Participants with OVC will receive an intravenous infusion of DS-6000a at the RDE. | |
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 study start
- 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, DS-1062a, DS-7300a)
- Has history or current presence of CNS metastases except for participants who have
completed radiotherapy or surgery ≥2 weeks before the start of 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 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 study
treatment
- Has a medical history of symptomatic congestive heart failure (New York Heart
Association classes II-IV) or a serious cardiac arrhythmia requiring treatment
- Lung-specific intercurrent clinically significant illnesses
- Has an uncontrolled infection requiring systemic therapy
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants With Dose-limiting toxicities (DLTs) |
Time Frame: | Day 1 to Day 21 in Cycle 1 (each cycle is 21 days) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve from Time Zero to 21 Days (AUC 21d) for DS-6000a 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) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time (AUClast) for DS-6000a 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) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic Analysis Maximum Plasma Concentration (Cmax) for DS-6000a 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) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic Analysis Lowest Plasma Concentration (Ctrough) for DS-6000a 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) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetic Analysis Time to Maximum Plasma Concentration (Tmax) for DS-6000a 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) |
Safety Issue: | |
Description: | |
Measure: | Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
Time Frame: | From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 24 months (each cycle is 21 days) |
Safety Issue: | |
Description: | ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR). |
Measure: | Duration of Response (DoR) Based on RECIST v1.1 |
Time Frame: | From date of first documented response to date of progression or death due to any cause (whichever occurs first), up to approximately 24 months |
Safety Issue: | |
Description: | DoR is defined as the duration from the first documented response to the date of progression or death due to any cause. |
Measure: | Disease Control Rate (DCR) Based on RECIST v1.1 |
Time Frame: | From start of treatment up to first documented response (CR, PR, or SD), disease progression, or death (due to any cause), up to approximately 24 months |
Safety Issue: | |
Description: | DCR is defined as the proportion of participants with BOR of CR, PR, or SD. |
Measure: | Clinical Benefit Rate (CBR) Based on RECIST v1.1 |
Time Frame: | 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 24 months |
Safety Issue: | |
Description: | 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. |
Measure: | Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Percentage of Participants Who Have Treatment-emergent ADA |
Time Frame: | 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 30-day safety follow up visit, up to approximately 24 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Daiichi Sankyo, Inc. |
Trial Keywords
- Renal Cell Carcinoma
- Ovarian Tumor
- DS-6000a
Last Updated
August 18, 2021