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

Phase I, Two-Part, Multi-Center, First-in-Human Study of DS-6000a in Subjects With Advanced Renal Cell Carcinoma and Ovarian Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Cell Carcinoma; Ovarian Tumor
• Intervention / Treatment: Drug: DS-6000a; Drug: DS-6000a

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.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: (US Sites) Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 908-992-6400; Email: CTRinfo@dsi.com

Study Locations

• Japan
  • Fukuoka, Japan, 811-1395
    • Recruiting
    • National Hospital Organization Kyusyu Cancer Center
  • Koto-Ku, Japan, 135-0063
    • Recruiting
    • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
    • Contact: Principal Investigator
  • Matsuyama, Japan, 791-0280
    • Recruiting
    • National Hospital Organization Shikoku Cancer Center
    • Contact: Principal Investigator
  • Nagaizumi, Japan, 411-8777
    • Recruiting
    • Shizuoka Cancer Center
    • Contact: Principal Investigator
  • Saitama, Japan, 350-1298
    • Recruiting
    • Saitama Medical University International Medical Center
    • Contact: Principal Investigator
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
      • Contact: Principal Investigator
    • Kashiwa-shi, Tokyo, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
      • Contact: Principal Investigator
• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Recruiting
      • Arizona Oncology Associates, PC HOPE (A)A HOPE)
      • Contact: Principal Investigator
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Rocky Mountain Cancer Center
      • Contact: Principal Investigator
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Recruiting
      • Florida Cancer Lake Mary
      • Contact: Site Coordinator
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Oklahoma University
      • Contact: Principal Investigator
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Withdrawn
      • Sydney Kimmel Cancer Center at Thomas Jefferson University Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt-Ingram Cancer Center
      • Contact: Site Coordinator
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology-Nashville
      • Contact: Principal Investigator

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Participants with ovarian cancer (OVC) or renal cell carcinoma (RCC) will receive an intravenous infusion of R-DXd (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; Other Names: R-DXd; Drug: DS-6000a; Intravenous administration at RDE on Day 1 of Cycle 1; Other Names: R-DXd
Experimental: Dose Expansion: Cohort B-1; Participants with RCC will receive an intravenous infusion of R-DXd at the RDE.	Drug: DS-6000a; Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1; Other Names: R-DXd; Drug: DS-6000a; Intravenous administration at RDE on Day 1 of Cycle 1; Other Names: R-DXd
Experimental: Dose Expansion: Cohort B-2; Participants with OVC will receive an intravenous infusion of R-DXd at the RDE.	Drug: DS-6000a; Intravenous administration at doses starting at 1.6 mg/kg on Day 1 of Cycle 1; Other Names: R-DXd; Drug: DS-6000a; Intravenous administration at RDE on Day 1 of Cycle 1; Other Names: R-DXd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 24 months
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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)
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)
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) (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)
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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2020
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Renal Cell Carcinoma; Ovarian Tumor; Raludotatug deruxtecan (R-DXd; DS-6000a)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma, Renal Cell; Carcinoma; Ovarian Neoplasms
• Other Study ID Numbers: DS6000-A-U101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No