This pan-tumor trial is designed as a signal-seeking trial to assess efficacy and safety of raludotatug deruxtecan (R-DXd) monotherapy in locally advanced or metastatic solid tumors with various cadherin-6 (CDH6) expression levels, including gynecological cancers (endometrial cancer, cervical cancer, and non-high-grade serous ovarian cancer) and genitourinary cancers (urothelial cancer and clear cell renal cell carcinoma \[ccRCC\]).
This trial is designed to evaluate the efficacy and safety of R-DXd in locally advanced or metastatic solid tumors with various CDH6 expression levels. Solid tumor types will include gynecological cancers (endometrial cancer, cervical cancer, and non-high-grade serous ovarian cancer) and genitourinary cancers (urothelial cancer and ccRCC). For all cohorts except ccRCC, the primary endpoint will be objective response rate (ORR) by investigator assessment per RECIST 1.1. For the ccRCC cohort, the primary endpoint will be disease control rate (DCR) by investigator assessment per RECIST 1.1. All cohorts will also have the assessment of safety and tolerability as another primary objective.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
IV administration Q3W
Objective Response Rate as Assessed by the Investigator (All Cohorts Except ccRCC)
Objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 criteria.
Time frame: Baseline up to 32 months
Disease Control Rate (DCR) as Assessed by the Investigator (ccRCC Cohort Only)
Disease control rate (DCR) is defined as proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (maintained for ≥5 weeks) according to RECIST version 1.1.
Time frame: Baseline up to 32 months
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) (All Cohorts)
Time frame: Baseline up to 32 months
Progression-free Survival (PFS) as Assessed by the Investigator
Progression-free survival (PFS) is defined as the time interval from the start date of trial intervention to the date of radiographic disease progression according to RECIST version 1.1 criteria or death due to any cause, whichever comes first.
Time frame: Baseline up to 32 months
Duration of Response (DoR) as Assessed by the Investigator
Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (CR or PR) that is subsequently confirmed to the date of the first documentation of radiographic disease progression according to RECIST version 1.1 criteria or death due to any cause, whichever occurs first.
Time frame: Baseline up to 32 months
Time to Response (TTR) as Assessed by the Investigator
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Northside Hospital
Marietta, Georgia, United States
University of Michigan Comprehensive Cancer Center Michigan Medicine
Ann Arbor, Michigan, United States
Astera Cancer Care
East Brunswick, New Jersey, United States
Women's Cancer Care Associates
Albany, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Clinical Research Alliance
Westbury, New York, United States
West Cancer Center and Research Institute
Germantown, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
UZ Leuven Gynaec onco
Leuven, Belgium
ZAS Sint-Augustinus
Wilrijk, Belgium
...and 38 more locations
Time to response (TTR) is defined as the time from the start date of trial intervention to the date of the first documentation of response (CR or PR) that is subsequently confirmed. TTR will be calculated for confirmed responders only.
Time frame: Baseline up to 32 months
Objective Response Rate as Assessed by the Investigator (ccRCC Cohort Only)
Objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 criteria.
Time frame: Baseline up to 32 months
Disease Control Rate (DCR) as Assessed by the Investigator (All Cohorts Except ccRCC Cohort)
Disease control rate (DCR) is defined as proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (maintained for ≥5 weeks) according to RECIST version 1.1.
Time frame: Baseline up to 32 months
Pharmacokinetic Parameter Maximum Concentration (Cmax) of R-DXd
Time frame: Cycles 1 and 3 Day 1 predose and end of infusion (EOI), 3 hours (hr), and 5 hr postdose; Cycle 1 Days 8, 15, and 22; Cycle 2 Day 1 predose and EOI postdose; Cycle 4 (and every 2 cycles thereafter) predose, up to 32 months (each cycle is 21 days)
The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have a Treatment-emergent ADA
Time frame: Baseline up to 32 months