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

NCT06172478 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: U31402-2772023-507641-29-00jRCT2031230575
• Study Type: interventional
• Target: 740
• Locations: 16 countries
• Sites: 84

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.

Conditions

Advanced Solid Tumor; Melanoma; Head and Neck Cancer; Gastric Cancer; Cervical Cancer; Endometrial Cancer; Bladder Cancer; Esophageal Cancer; Pancreatic Carcinoma; Prostate Cancer; Non-small Cell Lung Cancer (NSCLC); Lung Cancer; Breast Cancer; Ovarian Carcinoma

Keywords

Advanced Solid Tumor; Melanoma; Head and Neck Cancer; Gastric Cancer; Ovarian carcinoma; Cervical cancer; Endometrial cancer; Bladder cancer; Esophageal carcinoma; Pancreatic carcinoma; Prostate cancer; Patritumab Deruxtecan; HER3-DXd; U3-1402; Lung Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (16)

• Overall Number of Participants With Treatment-emergent Adverse Events Following HER3-DXd Monotherapy (All Cohorts)

  Baseline up to 27 months

• 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

• 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

• 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

• 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

Study Arms (1)

HER3-DXd Monotherapy

EXPERIMENTAL

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

Interventions

HER3-DXd DRUG

Intravenous infusion 5.6 mg/kg administered Q3W on Day 1 of each 21-day cycle

Also known as: Patritumab Deruxtecan, U3-1402

HER3-DXd Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for enrollment into the study:
• 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.
• Participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old).
• Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) as follows:
• Cutaneous (acral and non-acral) melanoma
• Histologically or cytologically confirmed cutaneous (acral or non-acral) melanoma
• 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
• 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.
• 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
• 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.
• Disease progression after having received treatment with ≥2 prior lines of therapy that include PBC with or without anti-PD-1 therapy.
• Ovarian Carcinoma

You may not qualify if:

• Participants who meet any of the following criteria will be disqualified from entering the study:
• 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.
• Has nasopharyngeal cancer.
• Has mucosal or uveal melanoma.
• 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.
• Has clinically severe respiratory compromise (based on the investigator's assessment) resulting from intercurrent pulmonary illnesses
• 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.
• 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).
• Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following:
• Adequately treated nonmelanoma skin cancer
• Adequately treated intraepithelial carcinoma of the cervix
• Any other curatively treated in situ disease
• 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
• Has previously received topoisomerase-1 inhibitors (e.g., irinotecan) treatment in the advanced or metastatic disease setting.

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (84)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06510, United States

RECRUITING

AdventHealth Medical Group Oncology Research at Celebration

Kissimmee, Florida, 34747, United States

RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

Health Partners Frauenshuh Cancer Center

Saint Louis Park, Minnesota, 55426, United States

RECRUITING

Health Partners Cancer Center at Regions Hospital

Saint Paul, Minnesota, 55101, United States

RECRUITING

Washington University, School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Roswell Park Cancer Institute IDS

Buffalo, New York, 14203, United States

RECRUITING

Memorial Sloan Kettering Hospital

New York, New York, 10065, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Chris O'Brien Lifehouse

Camperdown, 2050, Australia

RECRUITING

Icon Cancer Centre Chermside

Chermside, 4032, Australia

RECRUITING

Monash Medical Centre Clayton

Clayton, 3168, Australia

RECRUITING

Icon Cancer Centre Hobart

Hobart, 7000, Australia

RECRUITING

Icon Cancer Centre Townsville

Hyde Park, 4812, Australia

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, Belgium

RECRUITING

UZA

Edegem, 2650, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

Universitair Ziekenhuis Brussel

Jette, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

Sunnybrook Research Institute

Toronto, M4N 3M5, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, M5G2M9, Canada

RECRUITING

BC Cancer - Vancouver

Vancouver, V5Z4E6, Canada

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, 510060, China

RECRUITING

Chu Bordeaux

Bordeaux, 33000, France

RECRUITING

Centre Georges Franăois Leclerc

Dijon, 21079, France

RECRUITING

Hopital Claude Huriez - Chu Lille

Lille, 59000, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Hăpital de La Timone

Marseille, 13005, France

RECRUITING

Chu Nantes - Hătel Dieu

Nantes, 44093, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31100, France

RECRUITING

ICL - Alexis Vautrin

Vandœuvre-lès-Nancy, 54500, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Krankenhaus Nordwest GmbH

Frankfurt, 60488, Germany

RECRUITING

Bacs-Kiskun Varmegyei Oktatokorhaz

Kecskemét, 6000, Hungary

RECRUITING

Humanitas Gavazzeni

Bergamo, 24125, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

RECRUITING

AOU Federico II - Oncologia Clinica

Naples, 80131, Italy

RECRUITING

Centro Ricerche Cliniche di Verona s.r.l.

Verona, 37134, Italy

RECRUITING

Saitama Medical University International Medical Center

Hidaka, 350-1298, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, 277-8577, Japan

RECRUITING

NHO Shikoku Cancer Center

Matsuyama, 791-0245, Japan

RECRUITING

Shizuoka Cancer Center

Nagaizumi-cho, 411-8777, Japan

RECRUITING

Aichi Cancer Center Hospital

Nagoya, 464-8681, Japan

RECRUITING

Kindai University Hospital

Osakasayama-shi, 589-8511, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, 104-0045, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

RECRUITING

Yokohama City University Medical Center

Yokohama, 232-0024, Japan

RECRUITING

Amsterdam UMC locatie Vumc

Amsterdam, 1081 HV, Netherlands

RECRUITING

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Leids Universitair Medisch Centrum

Leiden, 2333 ZG, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

RECRUITING

Radboud University Medical Center

Nijmegen, 6525 GA, Netherlands

RECRUITING

Akershus universitetssykehus

Lørenskog, 1478, Norway

RECRUITING

Haukeland universitetssjukehus

Lørenskog, 1478, Norway

RECRUITING

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, 0379, Norway

RECRUITING

Cha Bundang Medical Center, Cha University

Seongnam, 13496, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, 28009, Spain

RECRUITING

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

HOSPITAL REGIONAL UNIVERSITARIO de MALAGA AVDA.

Málaga, 29010, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

RECRUITING

University Hospital Coventry

Coventry, CV2 2DX, United Kingdom

RECRUITING

Barts Hospital

London, EC1A 7BE, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

RECRUITING

Nottingham City Hospital Campus

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 41088723 DERIVED

MeSH Terms

Conditions

Melanoma; Head and Neck Neoplasms; Stomach Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Urinary Bladder Neoplasms; Esophageal Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Breast Neoplasms

Interventions

patritumab deruxtecan

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Esophageal Diseases; Pancreatic Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Central Study Contacts

Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

9089926400; CTRinfo@dsi.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 15, 2023
• Study Start: February 26, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 10, 2028
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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.

Locations

US (13); FR (9); ES (9); CN (1); GB (4); IT (4); KR (6); TW (5); NO (3); DE (1); JP (9); NL (5); AU (5); BE (5); CA (4); HU (1)