Clinical Trials /

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

NCT04707248

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.

Related Conditions:
  • Malignant Ovarian Neoplasm
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
DS-6000aDose Escalation
DS-6000aDose 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

NameTypeDescriptionInterventions
Dose EscalationExperimentalParticipants with ovarian cancer (OVC) or renal cell carcinoma (RCC) will receive an intravenous infusion of DS-6000a (starting dose 1.6 mg/kg).
  • DS-6000a
Dose Expansion: Cohort B-1ExperimentalParticipants with RCC will receive an intravenous infusion of DS-6000a at the RDE.
  • DS-6000a
Dose Expansion: Cohort B-2ExperimentalParticipants with OVC will receive an intravenous infusion of DS-6000a at the RDE.
  • 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
      
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

July 13, 2021