A Study of HER3-DXd in Subjects With Locally Advanced or Metastatic Solid Tumors

HERTHENA-PanTumor01 (U31402-277): A Phase 2, Multicenter, Multicohort, Open-Label, Proof of Concept Study of Patritumab Deruxtecan (HER3-DXd; U3-1402) in Subjects With Locally Advanced or Metastatic Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Cervical Cancer; Breast Cancer; Head and Neck Cancer; Gastric Cancer; Esophageal Cancer; Lung Cancer; Prostate Cancer; Bladder Cancer; Advanced Solid Tumor; Endometrial Cancer; Non-small Cell Lung Cancer (NSCLC); Ovarian Carcinoma; Pancreatic Carcinoma
• Intervention / Treatment: Drug: HER3-DXd

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.

• Study Type: Interventional
• Enrollment (Estimated): 740
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daiichi Sankyo Contact for Clinical Trial Information; Phone Number: 9089926400; Email: CTRinfo@dsi.com

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Recruiting
    • Chris O'Brien Lifehouse
  • Chermside, Australia, 4032
    • Recruiting
    • Icon Cancer Centre Chermside
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Medical Centre Clayton
  • Hobart, Australia, 7000
    • Recruiting
    • Icon Cancer Centre Hobart
  • Hyde Park, Australia, 4812
    • Recruiting
    • Icon Cancer Centre Townsville
• Belgium
  • Brussels, Belgium
    • Recruiting
    • Cliniques universitaires Saint-Luc
  • Edegem, Belgium, 2650
    • Recruiting
    • UZA
  • Ghent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
  • Jette, Belgium
    • Recruiting
    • Universitair Ziekenhuis Brussel
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
• Canada
  • Toronto, Canada, M5G2M9
    • Recruiting
    • Princess Margaret Cancer Centre
  • Toronto, Canada, M4N 3M5
    • Recruiting
    • Sunnybrook Research Institute
  • Vancouver, Canada, V5Z4E6
    • Recruiting
    • BC Cancer - Vancouver
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
• China
  • Chengdu, China, 610098
    • Recruiting
    • West China Hospital, Sichuan University
  • Guangzhou, China, 510060
    • Recruiting
    • Sun Yat-sen University Cancer Center
• France
  • Bordeaux, France, 33000
    • Recruiting
    • CHU Bordeaux
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges Franăois Leclerc
  • Lille, France, 59000
    • Recruiting
    • Hopital Claude Huriez - CHU Lille
  • Lyon, France, 69008
    • Recruiting
    • Centre Leon Berard
  • Marseille, France, 13005
    • Recruiting
    • Hăpital de La Timone
  • Nantes, France, 44093
    • Recruiting
    • Chu Nantes - Hătel Dieu
  • Toulouse, France, 31100
    • Recruiting
    • Institut Claudius Regaud
  • Vandœuvre-lès-Nancy, France, 54500
    • Recruiting
    • ICL - Alexis Vautrin
  • Villejuif, France, 94805
    • Recruiting
    • Institut Gustave Roussy
• Germany
  • Frankfurt, Germany, 60488
    • Recruiting
    • Krankenhaus Nordwest GmbH
• Hungary
  • Kecskemét, Hungary, 6000
    • Recruiting
    • Bács-Kiskun Vármegyei Oktatókórház
• Italy
  • Bergamo, Italy, 24125
    • Recruiting
    • Humanitas Gavazzeni
  • Genova, Italy, 16132
    • Recruiting
    • IRCCS Ospedale Policlinico San Martino
  • Naples, Italy, 80131
    • Recruiting
    • AOU Federico II - Oncologia Clinica
  • Verona, Italy, 37134
    • Recruiting
    • Centro Ricerche Cliniche di Verona S.r.l.
• Japan
  • Hidaka, Japan, 350-1298
    • Recruiting
    • Saitama Medical University International Medical Center
  • Kashiwa-shi, Japan, 277-8577
    • Recruiting
    • National Cancer Center Hospital East
    • Contact: See Central Contact
  • Matsuyama, Japan, 791-0245
    • Recruiting
    • Nho Shikoku Cancer Center
    • Contact: See Central Contact
  • Nagaizumi-cho, Japan, 411-8777
    • Recruiting
    • Shizuoka Cancer Center
    • Contact: See Central Contact
  • Nagoya, Japan, 464-8681
    • Recruiting
    • Aichi Cancer Center Hospital
  • Osakasayama-shi, Japan, 589-8511
    • Recruiting
    • Kindai University Hospital
    • Contact: See Central Contact
  • Tokyo, Japan, 104-0045
    • Recruiting
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • Recruiting
    • Cancer Institute Hospital of JFCR
  • Yokohama, Japan, 232-0024
    • Recruiting
    • Yokohama City University Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • Amsterdam UMC Locatie VUMC
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Universitair Medisch Centrum Groningen
  • Leiden, Netherlands, 2333 ZG
    • Recruiting
    • Leids Universitair Medisch Centrum
  • Maastricht, Netherlands, 6229 HX
    • Recruiting
    • Maastricht University Medical Center
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboud University Medical Center
• Norway
  • Lørenskog, Norway, 1478
    • Recruiting
    • Akershus Universitetssykehus
  • Lørenskog, Norway, 1478
    • Recruiting
    • Haukeland Universitetssjukehus
  • Oslo, Norway, 0379
    • Recruiting
    • Oslo Universitetssykehus HF, Radiumhospitalet
• South Korea
  • Seongnam, South Korea, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seongnam, South Korea, 13496
    • Recruiting
    • Cha Bundang Medical Center, Cha University
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08041
    • Recruiting
    • Hospital De La Santa Creu I Sant Pau
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital General Universitario Gregorio Marañón
  • Málaga, Spain, 29010
    • Recruiting
    • HOSPITAL REGIONAL UNIVERSITARIO de MALAGA AVDA.
  • Seville, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clinico Universitario de Valencia
• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: See Central Contact
  • Taipei, Taiwan, 100225
    • Recruiting
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • Recruiting
    • University Hospital Coventry
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free Hospital
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • Barts Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Recruiting
    • Nottingham City Hospital Campus
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Contact: Principal Investigator
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Cancer Center
  • Florida
    • Kissimmee, Florida, United States, 34747
      • Recruiting
      • AdventHealth Medical Group Oncology Research at Celebration
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins University
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55426
      • Recruiting
      • Health Partners Frauenshuh Cancer Center
    • Saint Paul, Minnesota, United States, 55101
      • Recruiting
      • Health Partners Cancer Center at Regions Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University, School of Medicine
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • Roswell Park Cancer Institute IDS
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Principal Investigator
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

Participants must meet all of the following criteria to be eligible for enrollment into the study:

1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all subjects to meet the baseline tumor tissue requirement.
2. Participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).

3. Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) as follows:

   Cutaneous (acral and non-acral) melanoma

   1. Histologically or cytologically confirmed cutaneous (acral or non-acral) melanoma

   2. Disease progression while on or after having received treatment with ≥1 prior line of anti-programmed cell death protein (PD-1) or anti-programmed death-ligand 1 (PD-L1) based therapy (previous use of other immune checkpoint inhibitors [ICIs] [ie, anti-CTLA4, anti- LAG-3] is acceptable). Prior anti-PD-(L)1 therapy in the adjuvant setting is allowed if there is recurrence within 12 weeks of the last dose. If the participant had BRAFm melanoma, they must have had disease progression on BRAF/MEK inhibitor therapy as well.

      Squamous cell carcinomas of the head and neck

   3. Squamous cell carcinoma of the head and neck (with a primary location of oral cavity,oropharynx, larynx, hypopharynx) that is human papillomavirus (HPV) positive or negative (as determined by local standard). Excludes tumor location in the nasopharynx, nasal cavity, paranasal sinuses, and unknown primary locations.

   4. Disease progression after having received treatment with ≥1 and <3 prior lines of systemic therapy in the unresectable recurrent or metastatic setting.

      Must have had disease progression on anti-PD-(L)1 (either as monotherapy or in combination with chemotherapy or other therapies). Must also have had disease progression on a platinum-based chemotherapy (PBC) regimen either in the recurrent or metastatic setting or in the locally advanced setting with curative intent.

      Gastric or GEJ adenocarcinoma

   5. Tumor tissue must be confirmed as negative for HER2 expression (immunohistochemistry [IHC] 0/1+ or IHC 2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.

   6. Disease progression after having received treatment with ≥2 prior lines of therapy that include PBC with or without anti-PD-1 therapy.

      Ovarian Carcinoma

   7. Pathologically documented high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

   8. Documented disease progression ≥4 weeks after the last dose of PBC and <6 months of last dose of PBC in the advanced or metastatic setting. Prior use of folate reductase alpha targeting antibody-drug conjugate (ADC) (ie, mirvetuximab soravtansine) is allowed.

      Cervical Cancer

   9. Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix.

   10. Disease progression after having received ≥1 line of systemic therapy in the recurrent or metastatic setting. This may include prior anti-PD-(L)1 treatment and/or tissue factor directed ADC (tisotumab vedotin [TV]) per regional standard of care.

       Endometrial Cancer

   11. Pathologically or cytologically documented endometrial cancer (carcinoma of any histological sub-type or endometrial carcinosarcoma), irrespective of microsatellite instability (MSI) or mismatch repair (MMR) status.

   12. Documented disease progression after having received ≥1 prior line of therapy (maximum of 3) PBC containing systemic treatment and an anti-PD(L)-1 therapy-containing regimen (combined or sequential) in the advanced/metastatic setting.

       Bladder Cancer

   13. Pathologically or cytologically documented locally advanced/unresectable or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant. Small cell/neuroendocrine tumors are not allowed even if mixed histology.

   14. Relapsed or progressed after treatment with ≥1 prior line of therapy (maximum of 3) that contains anti-PD-(L)1 therapy in the perioperative or metastatic setting. At least 1 line of therapy must also contain one of the following treatment modalities: chemotherapy or enfortumab vedotin. Prior fibroblast growth factor receptor (FGFR)-inhibitor treatment for those who are eligible are allowed.

       • Required treatments can be given in combination or sequentially
       • Prior cisplatin-based therapy or PD-(L)1 inhibitor therapy given for the treatment of muscle invasive urothelial carcinoma is counted as 1 line of therapy
       • The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy
       • Participants in the second-line setting who have previously received enfortumab vedotin and pembrolizumab in combination can be enrolled.

       Esophageal Carcinoma

   15. Pathologically or cytologically documented esophageal squamous cell carcinoma.

   16. Must have documented disease progression after having received 2 prior lines of therapy including previous PBC with or without an anti-PD-1 therapy-containing regimen (combined or sequential) in the advanced/metastatic setting.

       Pancreatic Carcinoma

   17. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma.

   18. Relapsed or disease progression after having received 1 prior line of systemic therapy in the locally advanced/metastatic setting.

       Prostate Cancer

   19. Pathologically or cytologically documented unresectable locally advanced or metastatic castration-resistant prostate cancer (CRPC).
   20. Adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
   21. Surgically or medically castrated, with testosterone levels of <50 ng/dL.
   22. Documented objective progression as determined by radiographic progression for subjects with measurable disease after androgen deprivation.
   23. Relapsed or disease progression after having received treatment with ≥1 of the following novel hormonal agents: abiraterone, enzalutamide, apalutamide, or darolutamide.

   24. Relapsed or disease progression after having received ≥1 cytotoxic chemotherapy regimen that included a taxane.

       Gastric Cancer 2L

   25. Must have had gastric or GEJ adenocarcinoma confirmed as negative for HER2 expression (IHC 0/1+ or IHC 2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
   26. Disease progression after having received treatment with only 1 prior line of systemic anti-cancer therapy that includes 5-FU-based chemotherapy with or without an anti-PD-1 therapy. For subjects whose tumors are claudin (CLDN) 18.2 positive, treatment with 5-FU based chemotherapy with CLDN18.2 directed therapy in the first-line setting is allowed.

   Non-small Cell Lung Cancer aa. Histologically or cytologically documented metastatic or locally advanced nonsquamous NSCLC not amenable to curative surgery or radiation bb. Documentation of absence of actionable driver mutation (ie, ALK rearrangement, BRAF V600E mutation, EGFR-activating mutations [exon 19 deletion or L858R mutation], EGFR exon 20 insertion mutation, HER2 mutation, KRAS G12C mutation, MET exon 14 skipping mutation, NTRK 1/2/3 gene fusion, RET rearrangement, or ROS1 rearrangement). New testing for these genomic alterations is not required for Screening.

   cc. Relapsed or disease progression after receiving only anti-PD-(L)1 and PBC (ie, platinum doublet) administered in combination or sequentially for metastatic disease.

   Breast Cancer dd. Pathologically documented breast cancer that is assessed as HER2 negative (IHC2+/ISH-, IHC1+, or IHC0 per ASCO/CAP guidelines), and HR positive (either ER and/or PgR positive [ER or PgR ≥1%] per ASCO/CAP guidelines). The HER2 and HR results must be from a tumor sample obtained in the metastatic setting.

   ee. Participant must have received one line of chemotherapy for mBC, but not more than one line and must have a clinically or radiologically documented evidence of tumor progression on or after CDK 4/6 inhibitor combined with endocrine therapy; previous treatments with phosphoinositide 3-kinase (PI3K) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, protein kinase B (PKB) inhibitors also known as AKT-inhibitors and poly ADP ribose polymerase (PARP)-inhibitors are allowed.

4. Has ≥1 measurable lesion on CT or MRI as per RECIST v1.1 by investigator assessment. Prostate cancer participants with bone only disease may be eligible.

5. Provides a pretreatment tumor tissue sample that meets 1 of the following collection requirements:

   1. Tumor biopsy from ≥1 lesion not previously irradiated and performed since progression with the most recent systemic cancer therapy regimen and prior to signature of the tissue ICF (ARCHIVAL PRETREATMENT sample).

      OR

   2. Newly obtained pretreatment tumor biopsy from ≥1 lesion not previously irradiated and amenable to sampling, after signature of tissue ICF (FRESH PRETREATMENT sample)
6. Has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at screening.

Exclusion Criteria

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Has HER2-positive gastric cancer as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
2. Has nasopharyngeal cancer.
3. Has mucosal or uveal melanoma.
4. Has a history of (non-infectious) interstitial lung disease (ILD), that required corticosteroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
5. Has clinically severe respiratory compromise (based on the investigator's assessment) resulting from intercurrent pulmonary illnesses

6. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone daily or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1.

   Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.

7. Had prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).

8. Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following:

   1. Adequately treated nonmelanoma skin cancer
   2. Adequately treated intraepithelial carcinoma of the cervix
   3. Any other curatively treated in situ disease
9. Has any evidence of severe or uncontrolled diseases (eg, active bleeding diatheses, active serious infection) psychiatric illness/social situations, geographical factors, substance abuse, or other factors that, in the investigator's opinion, make it high risk for the subject to participate in the study or that would jeopardize compliance with the protocol
10. Has previously received topoisomerase-1 inhibitors (e.g., irinotecan) treatment in the advanced or metastatic disease setting.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HER3-DXd Monotherapy; Participants with locally advanced unresectable or metastatic cancer (melanoma, head and neck, 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) will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W).

Drug: HER3-DXd; Intravenous infusion 5.6 mg/kg administered Q3W on Day 1 of each 21-day cycle; Other Names: U3-1402; Patritumab Deruxtecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Objective Response Rate Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)	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.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months
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

Outcome Measure	Measure Description	Time Frame
Overall Number of Participants With Treatment-emergent Adverse Events Following HER3-DXd Monotherapy (All Cohorts)	Adverse events (AEs) will be coded using MedDRA and AEs and will be graded by using NCI-CTCAE v5.0.	Baseline up to 27 months
Duration of Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)	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.	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
Clinical Benefit Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)	Clinical benefit rate (CBR) is the proportion of participants with a best overall response of confirmed CR, confirmed PR, or SD lasting ≥183 days.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months
Disease Control Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)	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.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months
Time to Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)	Time to response (TTR) will be calculated for confirmed responders only.	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
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
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
Pharmacokinetic Parameter Maximum Serum Concentration for HER3-DXd (All Cohorts)	Maximum serum concentration (Cmax) will be assessed using non-compartmental methods.	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)
Pharmacokinetic Parameter Time to Maximum Serum Concentration for HER3-DXd (All Cohorts)	Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.	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)
Pharmacokinetic Parameter Trough Serum Concentration (Ctrough) for HER3-DXd (All Cohorts)	Trough serum concentration (Ctrough) will be assessed using non-compartmental methods.	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)
Pharmacokinetic Parameter Area Under the Concentration Curve for HER3-DXd (All Cohorts)	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.	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)
Correlation Between HER3 Protein Expression and Efficacy	HER3 protein expression in tumor tissue as determined by IHC and correlation with ORR, DoR, and PFS.	From the start date of study drug up to approximately 27 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo

Publications and helpful links

General Publications

• Powles T, Bhatia A, Burtness B, Kogawa T, Nishina T, Nakayama I, Fountzilas C, Castillo DR, McKean M, Meric-Bernstam F, Colombo N, Smithy JW, Fayette J, Chandra S, Sternberg DW, Jin F, Sullivan K, Yueh S, Clinthorne G, Aguilo AE, Kudchadkar R, Hayashi H. HERTHENA-PanTumor01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated advanced solid tumors. Future Oncol. 2025 Oct;21(25):3283-3292. doi: 10.1080/14796694.2025.2561539. Epub 2025 Oct 14.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 10, 2028

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; Head and Neck Cancer; Lung Cancer; Bladder cancer; Gastric Cancer; Prostate cancer; Melanoma; Advanced Solid Tumor; Esophageal carcinoma; Cervical cancer; Endometrial cancer; HER3-DXd; Patritumab Deruxtecan; U3-1402; Ovarian carcinoma; Pancreatic carcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Esophageal Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Uterine Cervical Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Urinary Bladder Diseases; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Stomach Neoplasms; Lung Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Head and Neck Neoplasms; Melanoma; Urinary Bladder Neoplasms; Endometrial Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; patritumab deruxtecan
• Other Study ID Numbers: U31402-277; 2023-507641-29-00 (Other Identifier: EU CTIS); jRCT2031230575 (Other Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No