This study will evaluate the safety and efficacy of R-DXd therapy in participants with ovarian, peritoneal, or fallopian tube cancer.
This study will focus on R-DXd in participants with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancer. R-DXd is an antibody-drug conjugate that specifically binds to CDH6, which is overexpressed in tumor cells. The Phase 2 dose-optimization part of the study (Part A) intends to define the recommended dose based on safety and efficacy, while the Phase 3 (Part B) part of the study will compare R-DXd with Investigator's choice of chemotherapy and further evaluate efficacy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
860
R-DXd will be administered as an intravenously (IV) infusion
Paclitaxel will be administered as an IV infusion
Topotecan will be administered as an IV infusion
Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Assessment (Part A)
The ORR was defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR), by BICR assessment based on RECIST version 1.1.
Time frame: From date of randomization to data cut off, up to 18 months
Progression-free Survival (PFS) Based on BICR Assessment (Part B)
PFS is defined as the time from the date of randomization to the date of disease progression, defined as the first documented radiological progression or death due to any cause, whichever comes first.
Time frame: From date of randomization to data cut off, up to 26 months
Objective Response Rate (ORR) Based on Investigator Assessment
The ORR was defined as the percentage of participants who achieved Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR), by Investigator assessment based on RECIST version 1.1.
Time frame: From date of randomization to data cut off, up to 30 months
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause.
Time frame: From date of randomization to data cut off, up to 40 months
Duration of Response (DOR)
DoR is defined as the time from the date of the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of disease progression or death due to any cause, whichever occurs first.
Time frame: From date of randomization to data cut off, up to 40 months
Progression-free Survival (PFS) Based on BICR and Investigator Assessment
Medical Director Contact for Clinical Trial Information
CONTACT
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PLD will be administered as an IV infusion
Alaska Women's Cancer Care
Anchorage, Alaska, United States
ACTIVE_NOT_RECRUITINGYale University School of Medicine
New Haven, Connecticut, United States
RECRUITINGSylvester Comprehensive Cancer Center at Lennar
Coral Gables, Florida, United States
ACTIVE_NOT_RECRUITINGSylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
ACTIVE_NOT_RECRUITINGFlorida Cancer Specialists
Lake Mary, Florida, United States
ACTIVE_NOT_RECRUITINGSylvester Cancer Center
Miami, Florida, United States
ACTIVE_NOT_RECRUITINGMount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
ACTIVE_NOT_RECRUITINGSylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
ACTIVE_NOT_RECRUITINGCommunity MD Anderson Cancer Center- East
Indianapolis, Indiana, United States
ACTIVE_NOT_RECRUITINGCommunity MD Anderson Cancer Center- South
Indianapolis, Indiana, United States
ACTIVE_NOT_RECRUITING...and 110 more locations
PFS is defined as the time from the date of randomization to the date of disease progression, defined as the first documented radiological progression or death due to any cause.
Time frame: From date of randomization to data cut off, up to 30 months
Disease Control Rate (DCR)
DCR is defined as the proportion of participants who achieved a confirmed CR, PR, or stable disease maintained for ≥12 weeks, as assessed by BICR and investigator based on RECIST version 1.1
Time frame: From date of randomization to data cut off, up to 40 months
Time to Next Treatment (TTNT)
TTNT is defined as the time from randomization to the start date of the next line of therapy
Time frame: From date of randomization to data cut off, up to 40 months
Progression-free Survival 2 (PFS2) Based on Investigator Assessment
PFS2 is defined as the time from randomization to the first documented objective disease progression on next line therapy or death due to any cause, whichever comes first.
Time frame: From date of randomization to data cut off, up to 40 months
Percentage of Participants With Cancer Antigen 125 (CA-125) Response Rate
CA-125 response rate is defined as the percentage of participants with a reduction of 50% in CA-125 levels when compared to levels from a pretreatment sample, as assessed by blood sample based on Gynecological Cancer InterGroup criteria
Time frame: From baseline to data cut off, up to 40 months
Number of participants with Treatment-emergent Adverse Events (TEAEs)
TEAEs are defined as those AEs with a start or worsening date during the on-treatment period (from the first dose date to 40 days after the last dose date of study treatment).
Time frame: From first dose to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Maximum Plasma Drug Concentration (Cmax) of R-DXd
Time frame: From first dose to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Time to Reach Maximum Plasma Drug Concentration (Tmax) of R-DXP
Time frame: From first dose to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Area Under the Concentration-Time Curve (AUC) of R-DXd
Time frame: From first dose to data cut off, up to 40 months
Percentage of Participants With Treatment Emergent Antidrug Antibody (ADA)
Time frame: From baseline to data cut off, up to 40 months
Pharmacokinetic (PK) Analysis: Terminal Half-Life (t1/2) of R-DXd
Time frame: From first dose to data cut off, up to 40 months
Change from Baseline in Abdominal/gastrointestinal (GI) Symptoms (Part B)
Change from baseline in abdominal and gastrointestinal symptoms as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) OV28 abdominal/GI subscale
Time frame: From baseline to Week 12 and up to data cut off, up to 40 months
Change from Baseline in Fatigue/Pain Symptoms (Part B)
Change from baseline as measured by the EORTC QLQ C30 Fatigue/Pain subscale score
Time frame: From baseline to data cut off, up to 40 months
Time to Deterioration in Fatigue/Pain Symptoms (Part B)
Time to deterioration in pain from baseline as measured by the EORTC QLQ C30 Fatigue/Pain subscale score
Time frame: From baseline to data cut off, up to 40 months
Time to Deterioration in GI Symptoms (Part B)
Time to deterioration in pain from baseline as measured by the EORTC QLQ OV28 abdominal/GI subscale total score
Time frame: From baseline to data cut off, up to 40 months
Time to Deterioration in Disease Impacts (Part B)
Time to deterioration in selected subscales of EORTC QLQ C30; physical functioning, global health status, overall quality of life.
Time frame: From baseline to data cut off, up to 40 months
Change from Baseline in Disease Impacts (Part B)
Change from Baseline in selected subscales of EORTC QLQ C30; physical functioning, global health status, overall quality of life.
Time frame: From baseline to data cut off, up to 40 months
Cadherin-6 (CDH6) protein expression in tumor tissue as determined by immunochemistry assay and correlation with ORR, DoR, PFS and OS
CDH6 protein expression in tumor tissue as determined by immunohistochemistry.
Time frame: From baseline to data cut off, up to 40 months