Phase 2 Study of HER3-DXd in Locally Advanced or Metastatic Solid Tumors
- Conditions
- Advanced Solid TumorMelanomaHead and Neck CancerGastric CancerOvarian CarcinomaCervical CancerEndometrial CancerBladder CancerEsophageal CancerPancreatic Carcinoma
- Registration Number
- 2023-507641-29-00
- Lead Sponsor
- Daiichi Sankyo Inc.
- Brief Summary
This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma \[cutaneous/acral\], squamous cell carcinomas of the head and neck (SCCHN), HER2-negative gastric cancer ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer.
- Detailed Description
This study is designed to assess the safety and efficacy of HER3-DXd monotherapy in subjects with refractory locally advanced unresectable or metastatic solid tumors who have been previously treated with ≥1 prior line of systemic anticancer therapy.
The primary objective of the study is to assess the efficacy of HER3-DXd monotherapy for each type of indicated locally advanced unresectable or metastatic tumor. Secondary objectives include the assessment of safety and tolerability, efficacy, and pharmacokinetics of HER3-DXd monotherapy for each type of indicated locally advanced unresectable or metastatic tumor. HER3 protein expression in tumor tissue and its relationship with HER3-DXd efficacy will also be evaluated.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 740
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method The primary endpoint of the study is ORR as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). for all cohorts except Prostate cancer cohort The primary endpoint of the study is ORR as assessed by the investigator per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). for all cohorts except Prostate cancer cohort
For Prostate Cohort only:The PE is PSA50. Changes in PSA have been shown to correlate with OS, and this EP will allow for timely understanding of the antitumor activity in parallel with available safety endpoints. PSA50 response rate, defined as the proportion of patients with a ≥50% decrease in PSA level from baseline to the lowest postbaseline PSA result, confirmed by a consecutive PSA assessment at least 3 weeks later has been used in other clinical studies in prostate cancer For Prostate Cohort only:The PE is PSA50. Changes in PSA have been shown to correlate with OS, and this EP will allow for timely understanding of the antitumor activity in parallel with available safety endpoints. PSA50 response rate, defined as the proportion of patients with a ≥50% decrease in PSA level from baseline to the lowest postbaseline PSA result, confirmed by a consecutive PSA assessment at least 3 weeks later has been used in other clinical studies in prostate cancer
- Secondary Outcome Measures
Name Time Method Overall Number of Participants With Treatment-emergent Adverse Events Following HER3-DXd Monotherapy (All Cohorts) Baseline up to 27 months Adverse events (AEs) will be coded using MedDRA and AEs and will be graded by using NCI-CTCAE v5.0.
Duration of Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 27 months Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) to the date of the first documentation of progressive disease (PD) or death. The DoR will be calculated for responding participants (PR or CR) only.
Clinical Benefit Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months Clinical benefit rate (CBR) is the proportion of participants with a best overall response of confirmed CR, confirmed PR, or SD lasting ≥183 days.
Disease Control Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD (or non-CR/non-PD) by investigator assessment per RECIST v1.1.
Time to Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) From the start date of study drug to the date of the first documentation of response (CR or PR) that is subsequently confirmed, up to approximately 27 months Time to response (TTR) will be calculated for confirmed responders only.
Progression-free Survival As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) From the start date of study drug to the earlier date of the first objective documentation of radiographic disease progression as assessed by investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 27 months Overall Survival Following HER3-DXd Monotherapy (All Cohorts) From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 27 months Pharmacokinetic Parameter Maximum Serum Concentration for HER3-DXd (All Cohorts) Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days) Maximum serum concentration (Cmax) will be assessed using non-compartmental methods.
Pharmacokinetic Parameter Time to Maximum Serum Concentration for HER3-DXd (All Cohorts) Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days) Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.
Pharmacokinetic Parameter Trough Serum Concentration (Ctrough) for HER3-DXd (All Cohorts) Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days) Trough serum concentration (Ctrough) will be assessed using non-compartmental methods.
Pharmacokinetic Parameter Area Under the Concentration Curve for HER3-DXd (All Cohorts) Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8, Day 15 (each cycle is 21 days) Area under the concentration-time curve up to the last quantifiable time (AUClast) and Area under the concentration-time curve during dosing interval (AUCtau) will be assessed using non-compartmental methods.
Radiographic Progression-free Survival (rPFS) As Assessed by Prostate Cancer Working Group 3 (PCWG3) Criteria by the Investigator or Death Due to Any Cause Following HER3-DXd Monotherapy (Prostate Cancer Cohort Only) From the start date of study drug to the earlier date of the first objective documentation of radiographic disease progression as assessed per PCWG3 criteria by investigator or death due to any cause, whichever occurs first, up to approximately 27 months Proportion of Participants Achieving a ≥30% Decrease in PSA (Prostate Cancer Cohort Only) Baseline, each cycle before infusion (each cycle is 21 days), and end of treatment, up to approximately 27 months Time to First Subsequent Anticancer Therapy (TFST) (Prostate Cancer Cohort Only) From the start date of study drug to initiation of the first subsequent anticancer therapy or death, whichever occurs first, up to approximately 27 months Time to First Symptomatic Skeletal-Related Event (SSRE) (Prostate Cancer Cohort Only) From start date of study drug to the first occurrence of any of the following: Use of EBRT, New symptomatic pathologic bone fracture, Spinal cord compression, A tumor-related orthopedic surgical intervention, up to approximately 27 months Correlation Between HER3 Protein Expression and Efficacy From the start date of study drug up to approximately 27 months HER3 protein expression in tumor tissue as determined by IHC and correlation with ORR, DoR, and PFS.
Trial Locations
- Locations (75)
City of Hope
🇺🇸Duarte, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
AdventHealth Medical Group Oncology Research at Celebration
🇺🇸Kissimmee, Florida, United States
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Health Partners Frauenshuh Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Health Partners Cancer Center at Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
Washington University, School of Medicine
🇺🇸Saint Louis, Missouri, United States
Roswell Park Cancer Institute IDS
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering Hospital
🇺🇸New York, New York, United States
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