Clinical trial NCT04707248: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Renal Cell Carcinoma
Ovarian Tumor
Keywords: Renal Cell Carcinoma
Ovarian Tumor
Raludotatug deruxtecan (R-DXd; DS-6000a)
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-01-13
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 adverse events 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.

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, datopotamab deruxtecan, ifinatamab deruxtecan, DS-3939)
* 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 cardiac arrhythmia requiring treatment
* Lung-specific intercurrent clinically significant illnesses
* Has an uncontrolled infection requiring systemic therapy

Primary outcomes:
measure: Number of Participants With Dose-limiting toxicities (DLTs)
timeFrame: Day 1 to Day 21 in Cycle 1 (each cycle is 21 days)
measure: Number of Participants Reporting Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest
timeFrame: From start of treatment up to 40 days after last dose, up to approximately 52 months
measure: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (Dose Expansion)
timeFrame: From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 52 months (each cycle is 21 days)
Secondary outcomes:
measure: Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve from Time Zero to 21 Days (AUC 21d) for R-DXd and its Metabolites
timeFrame: 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)
measure: Pharmacokinetic Analysis Area Under the Plasma Concentration-Time Curve Up to the Last Quantifiable Time (AUClast) for R-DXd and its Metabolites
timeFrame: 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)
measure: Pharmacokinetic Analysis Maximum Plasma Concentration (Cmax) for R-DXd and its Metabolites
timeFrame: 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)
measure: Pharmacokinetic Analysis Lowest Plasma Concentration (Ctrough) for R-DXd and its Metabolites
timeFrame: 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)
measure: Pharmacokinetic Analysis Time to Maximum Plasma Concentration (Tmax) for R-DXd and its Metabolites
timeFrame: 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)
measure: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Per Investigator and Blinded Independent Central Review (Dose Escalation)
timeFrame: From start of treatment (Cycle 1, Day 1) up to disease progression, up to approximately 52 months (each cycle is 21 days)
measure: Duration of Response (DoR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review
timeFrame: From date of first documented response to date of progression or death due to any cause (whichever occurs first), up to approximately 52 months
measure: Disease Control Rate (DCR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review
timeFrame: From start of treatment up to first documented response (CR, PR, or SD), disease progression, or death (due to any cause), up to approximately 52 months
measure: Clinical Benefit Rate (CBR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review
timeFrame: 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 52 months
measure: Time to Response (TTR) Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review
timeFrame: From start of treatment up to first documented response (CR, PR, or SD), disease progression, or death (due to any cause), up to approximately 52 months
measure: Progression-free Survival Based on RECIST v1.1 Per Investigator and Blinded Independent Central Review
timeFrame: From start of treatment up to disease progression or death (due to any cause), up to approximately 52 months
measure: Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Percentage of Participants Who Have Treatment-emergent ADA
timeFrame: 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 52 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC HOPE (A)A HOPE)
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Lake Mary
state: Florida
city: Oklahoma City
country: United States
facility: Oklahoma University
state: Oklahoma
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyusyu Cancer Center
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Nagaizumi
country: Japan
facility: Shizuoka Cancer Center
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: