Back to resultsA Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors
Primary Purpose
Renal Cell Carcinoma, Ovarian Tumor
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DS-6000a
DS-6000a
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring Renal Cell Carcinoma, Ovarian Tumor, Raludotatug deruxtecan (R-DXd; DS-6000a)
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
Sites / Locations
- Arizona Oncology Associates, PC HOPE (A)A HOPE)Recruiting
- Rocky Mountain Cancer CenterRecruiting
- Florida Cancer Lake MaryRecruiting
- Oklahoma UniversityRecruiting
- Sydney Kimmel Cancer Center at Thomas Jefferson University Hospital
- Tennessee Oncology-NashvilleRecruiting
- Vanderbilt-Ingram Cancer CenterRecruiting
- National Cancer Center HospitalRecruiting
- National Cancer Center Hospital EastRecruiting
- National Hospital Organization Kyusyu Cancer CenterRecruiting
- The Cancer Institute Hospital of Japanese Foundation for Cancer ResearchRecruiting
- National Hospital Organization Shikoku Cancer CenterRecruiting
- Shizuoka Cancer CenterRecruiting
- Saitama Medical University International Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Dose Escalation
Dose Expansion: Cohort B-1
Dose Expansion: Cohort B-2
Arm Description
Participants with ovarian cancer (OVC) or renal cell carcinoma (RCC) will receive an intravenous infusion of R-DXd (starting dose 1.6 mg/kg).
Participants with RCC will receive an intravenous infusion of R-DXd at the RDE.
Participants with OVC will receive an intravenous infusion of R-DXd at the RDE.
Outcomes
Primary Outcome Measures
Number of Participants With Dose-limiting toxicities (DLTs)
Number of Participants Reporting Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest
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).
Secondary Outcome Measures
Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve from Time Zero to 21 Days (AUC 21d) for R-DXd and its Metabolites
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
Pharmacokinetic Analysis Lowest Plasma Concentration (Ctrough) for R-DXd and its Metabolites
Pharmacokinetic Analysis Time to Maximum Plasma Concentration (Tmax) for R-DXd and its Metabolites
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Dose Escalation)
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
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
DCR is defined as the proportion of participants with BOR of CR, PR, or SD.
Clinical Benefit Rate (CBR) Based on RECIST v1.1
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
Full Information
NCT ID
NCT04707248
First Posted
December 16, 2020
Last Updated
September 12, 2023
Sponsor
Daiichi Sankyo, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04707248
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 22, 2020 (Actual)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
October 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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 side effects 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma, Ovarian Tumor
Keywords
Renal Cell Carcinoma, Ovarian Tumor, Raludotatug deruxtecan (R-DXd; DS-6000a)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
140 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
Participants with ovarian cancer (OVC) or renal cell carcinoma (RCC) will receive an intravenous infusion of R-DXd (starting dose 1.6 mg/kg).
Arm Title
Dose Expansion: Cohort B-1
Arm Type
Experimental
Arm Description
Participants with RCC will receive an intravenous infusion of R-DXd at the RDE.
Arm Title
Dose Expansion: Cohort B-2
Arm Type
Experimental
Arm Description
Participants with OVC will receive an intravenous infusion of R-DXd at the RDE.
Intervention Type
Drug
Intervention Name(s)
DS-6000a
Other Intervention Name(s)
R-DXd
Intervention Description
Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1
Intervention Type
Drug
Intervention Name(s)
DS-6000a
Other Intervention Name(s)
R-DXd
Intervention Description
Intravenous administration at RDE on Day 1 of Cycle 1
Primary Outcome Measure Information:
Title
Number of Participants With Dose-limiting toxicities (DLTs)
Time Frame
Day 1 to Day 21 in Cycle 1 (each cycle is 21 days)
Title
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 24 months
Title
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Dose Expansion)
Description
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 24 months (each cycle is 21 days)
Secondary Outcome Measure Information:
Title
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)
Title
Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time (AUClast) 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)
Title
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)
Title
Pharmacokinetic Analysis Lowest Plasma Concentration (Ctrough) 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)
Title
Pharmacokinetic Analysis Time to Maximum Plasma Concentration (Tmax) 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)
Title
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Dose Escalation)
Description
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 24 months (each cycle is 21 days)
Title
Duration of Response (DoR) Based on RECIST v1.1
Description
DoR is defined as the duration from the first documented response to the date of progression or death due to any cause.
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
Title
Disease Control Rate (DCR) Based on RECIST v1.1
Description
DCR is defined as the proportion of participants with BOR of CR, PR, or SD.
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
Title
Clinical Benefit Rate (CBR) Based on RECIST v1.1
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.
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
Title
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 40-day safety follow up visit, up to approximately 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 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 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 serious cardiac arrhythmia requiring treatment
Lung-specific intercurrent clinically significant illnesses
Has an uncontrolled infection requiring systemic therapy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
(US sites) Daiichi Sankyo Contact for Clinical Trial Information
Phone
908-992-6400
Email
CTRinfo@dsi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology Associates, PC HOPE (A)A HOPE)
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85711
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
Florida Cancer Lake Mary
City
Lake Mary
State/Province
Florida
ZIP/Postal Code
32746
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Coordinator
Facility Name
Oklahoma University
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
Sydney Kimmel Cancer Center at Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Withdrawn
Facility Name
Tennessee Oncology-Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Coordinator
Facility Name
National Cancer Center Hospital
City
Chuo Ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
National Cancer Center Hospital East
City
Kashiwa-shi
State/Province
Tokyo
ZIP/Postal Code
277-8577
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
National Hospital Organization Kyusyu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Individual Site Status
Recruiting
Facility Name
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
City
Koto-Ku
ZIP/Postal Code
135-0063
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
National Hospital Organization Shikoku Cancer Center
City
Matsuyama
ZIP/Postal Code
791-0280
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
Shizuoka Cancer Center
City
Nagaizumi
ZIP/Postal Code
411-8777
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
Facility Name
Saitama Medical University International Medical Center
City
Saitama
ZIP/Postal Code
350-1298
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
IPD Sharing Time Frame
Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
IPD Sharing Access Criteria
Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/
Learn more about this trial
A Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors
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