A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation Participants with ovarian cancer (OVC) or renal cell carcinoma (RCC) will receive an intravenous infusion of DS-6000a (starting dose 1.6 mg/kg). |
Drug: DS-6000a
Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1
|
| Experimental: Dose Expansion: Cohort B-1 Participants with RCC will receive an intravenous infusion of DS-6000a at the RDE. |
Drug: DS-6000a
Intravenous administration at RDE on Day 1 of Cycle 1
|
| Experimental: Dose Expansion: Cohort B-2 Participants with OVC will receive an intravenous infusion of DS-6000a at the RDE. |
Drug: DS-6000a
Intravenous administration at RDE on Day 1 of Cycle 1
|
Outcome Measures
Primary Outcome Measures
- 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 30 days after last dose, up to approximately 24 months]
Secondary Outcome Measures
- Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve from Time Zero to 21 Days (AUC 21d) for DS-6000a 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 Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time (AUClast) for DS-6000a 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 DS-6000a 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 Lowest Plasma Concentration (Ctrough) for DS-6000a 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 DS-6000a 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) [From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 24 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 [From date of first documented response to date of progression or death due to any cause (whichever occurs first), up to approximately 24 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 [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]
DCR is defined as the proportion of participants with BOR of CR, PR, or SD.
- Clinical Benefit Rate (CBR) Based on RECIST v1.1 [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]
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.
- 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 30-day safety follow up visit, up to approximately 24 months]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Florida Cancer Lake Mary | Lake Mary | Florida | United States | 32746 |
| 2 | Oklahoma University | Oklahoma City | Oklahoma | United States | 73104 |
| 3 | Sydney Kimmel Cancer Center at Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
| 4 | Tennessee Oncology-Nashville | Nashville | Tennessee | United States | 37203 |
| 5 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 6 | National Cancer Center Hospital | Chuo Ku | Tokyo | Japan | 104-0045 |
| 7 | National Cancer Center Hospital East | Kashiwa-shi | Tokyo | Japan | 277-8577 |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
Investigators
- Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DS6000-A-U101