A Study of HER3-DXd in Subjects With Locally Advanced or Metastatic Solid Tumors
- Conditions
- Advanced Solid TumorMelanomaBladder CancerCervical CancerEsophageal CancerGastric CancerOvarian CarcinomaPancreatic CarcinomaHead and Neck CancerEndometrial Cancer
- Interventions
- Drug: HER3-DXd
- Registration Number
- NCT06172478
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma \[cutaneous/acral\], squamous cell carcinomas of the head and neck (SCCHN), and HER2-negative gastric cancerovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, and prostate cancer.
- Detailed Description
This study is designed to assess the safety and efficacy of HER3-DXd monotherapy in subjects with refractory locally advanced 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 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 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
- 400
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HER3-DXd Monotherapy HER3-DXd Participants with locally advanced or metastatic cancer (melanoma, head and neck, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, and prostate cancer) will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W).
- Primary Outcome Measures
Name Time Method Number of Participants With Objective Response Rate 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 Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Proportion of Participants Achieving a ≥50% 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
- 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.
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.
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; Cycle 1: Day 15 (each cycle is 21 days) Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.
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.
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 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; Cycle 1: Day 15 (each cycle is 21 days) Trough serum concentration (Ctrough) will be assessed using non-compartmental methods.
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 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; Cycle 1: Day 15 (each cycle is 21 days) Maximum serum concentration (Cmax) 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; Cycle 1: 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 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 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
Trial Locations
- Locations (61)
City of Hope
🇺🇸Duarte, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, 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
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, Australia
Icon Cancer Centre Chermside
🇦🇺Chermside, Australia
Monash Medical Centre Clayton
🇦🇺Clayton, Australia
Icon Cancer Centre Hobart
🇦🇺Hobart, Australia
Icon Cancer Centre Townsville
🇦🇺Hyde Park, Australia
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
UZA
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Universitair Ziekenhuis Brussel
🇧🇪Jette, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Chu Bordeaux
🇫🇷Bordeaux, France
Centre Georges Franăois Leclerc
🇫🇷Dijon, France
Hopital Claude Huriez - Chu Lille
🇫🇷Lille, France
Centre Léon Bérard
🇫🇷Lyon, France
Hăpital de La Timone
🇫🇷Marseille, France
Chu Nantes - Hătel Dieu
🇫🇷Nantes, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Saitama Medical University International Medical Center
🇯🇵Hidaka, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Japan
NHO Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya, Japan
Kindai University Hospital
🇯🇵Osakasayama-shi, Japan
Shizuoka Cancer Center
🇯🇵Sunto-gun, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Yokohama City University Medical Center
🇯🇵Yokohama, Japan
Cha Bundang Medical Center, Cha University
🇰🇷Seongnam, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
HOSPITAL REGIONAL UNIVERSITARIO de MALAGA AVDA.
🇪🇸Málaga, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
University Hospital Coventry
🇬🇧Coventry, United Kingdom
Barts Hospital
🇬🇧London, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Nottingham City Hospital Campus
🇬🇧Nottingham, United Kingdom