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

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ClinicalTrials.gov Identifier: NCT04707248
Recruitment Status : Recruiting
First Posted : January 13, 2021
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

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
Renal Cell Carcinoma Ovarian Tumor Drug: DS-6000a 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 25, 2021
Estimated Primary Completion Date : February 1, 2023
Estimated Study Completion Date : February 1, 2023


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




Primary Outcome Measures :
  1. Number of Participants With Dose-limiting toxicities (DLTs) [ Time Frame: Day 1 to Day 21 in Cycle 1 (each cycle is 21 days) ]
  2. 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 30 days after last dose, up to approximately 24 months ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
    ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR).

  7. 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 ]
    DoR is defined as the duration from the first documented response to the date of progression or death due to any cause.

  8. 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 ]
    DCR is defined as the proportion of participants with BOR of CR, PR, or SD.

  9. 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 ]
    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.

  10. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04707248


Contacts
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Contact: (US sites) Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com

Locations
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United States, Florida
Florida Cancer Lake Mary Recruiting
Lake Mary, Florida, United States, 32746
Contact: Site Coordinator         
United States, Oklahoma
Oklahoma University Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Principal Investigator         
United States, Pennsylvania
Sydney Kimmel Cancer Center at Thomas Jefferson University Hospital Withdrawn
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Tennessee Oncology-Nashville Recruiting
Nashville, Tennessee, United States, 37203
Contact: Principal Investigator         
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Site Coordinator         
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT04707248    
Other Study ID Numbers: DS6000-A-U101
First Posted: January 13, 2021    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
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.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo, Inc.:
Renal Cell Carcinoma
Ovarian Tumor
DS-6000a
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders