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

Renal Cell Carcinoma Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04707248
• Other study ID #: DS6000-A-U101
• Status: Recruiting
• Phase: Phase 1
• Start date: December 22, 2020
• Est. completion date: October 31, 2024

Study information

• Verified date: December 2023
• Source: Daiichi Sankyo, Inc.
• Contact: (US sites) Daiichi Sankyo Contact for Clinical Trial Information
• Phone: 908-992-6400
• Email: CTRinfo[@]dsi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Ovarian Neoplasms
• Ovarian Tumor
• Renal Cell Carcinoma

Intervention

Drug:
• DS-6000a
Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1
• DS-6000a
Intravenous administration at RDE on Day 1 of Cycle 1

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	National Hospital Organization Kyusyu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa-shi	Tokyo
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-Ku
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama
Japan	Shizuoka Cancer Center	Nagaizumi
Japan	Saitama Medical University International Medical Center	Saitama
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	Florida Cancer Lake Mary	Lake Mary	Florida
United States	Tennessee Oncology-Nashville	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Oklahoma University	Oklahoma City	Oklahoma
United States	Sydney Kimmel Cancer Center at Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Arizona Oncology Associates, PC HOPE (A)A HOPE)	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose-limiting toxicities (DLTs)		Day 1 to Day 21 in Cycle 1 (each cycle is 21 days)
Primary	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 24 months
Primary	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).	From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 24 months (each cycle is 21 days)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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).	From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 24 months (each cycle is 21 days)
Secondary	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.	From date of first documented response to date of progression or death due to any cause (whichever occurs first), up to approximately 24 months
Secondary	Disease Control Rate (DCR) Based on RECIST v1.1	DCR is defined as the proportion of participants with BOR of CR, PR, or SD.	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
Secondary	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.	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
Secondary	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 24 months