New drug targets Hard-to-Treat cancers in large trial

NCT ID NCT06172478

Disease control Sponsor: Daiichi Sankyo Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Sep 18, 2026 · Updated 10 times

Summary

This phase 2 trial is testing an experimental drug called patritumab deruxtecan (HER3-DXd) in 740 people with advanced solid tumors, including melanoma, lung, breast, and other cancers. The drug is given by IV every three weeks. The main goal is to see if the drug shrinks tumors. Researchers are also monitoring side effects. This study is recruiting now.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Patritumab deruxtecan (HER3-DXd)
What this could lead to: If successful, this could provide a new treatment option for many types of advanced solid tumors that have not responded to other therapies.
What could go wrong: This is an early-phase, proof-of-concept study, so the drug may not shrink tumors or improve survival. Side effects could be significant, and results may not apply to all cancer types tested.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 740 people

The number the study aims to enrol. It can still change while the study runs.

Started

Feb 2024

Expected to finish

Oct 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.

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Conditions

The condition(s) this trial relates to.

breast cancer breast neoplasm carcinoma of esophagus cervical cancer cutaneous melanoma endometrial cancer endometrium neoplasm esophageal cancer Esophageal Neoplasms exocrine pancreatic carcinoma fallopian tube cancer fallopian tube carcinoma gastric adenocarcinoma gastric cancer gastric neoplasm head and neck cancer Head and Neck Neoplasms head and neck squamous cell carcinoma lung cancer lung neoplasm melanoma non-small cell lung carcinoma ovarian cancer ovarian carcinoma ovarian serous adenocarcinoma pancreatic adenocarcinoma pancreatic neoplasm primary peritoneal carcinoma prostate cancer urinary bladder carcinoma Urinary Bladder Neoplasms Uterine Cervical Neoplasms

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced solid tumor Bladder cancer Breast cancer Cervical cancer Endometrial cancer Esophageal cancer Gastric cancer Head and neck cancer Lung cancer Melanoma Non-small cell lung cancer (NSCLC) Ovarian carcinoma Pancreatic carcinoma Prostate cancer

How to take part

Only the study team decides who joins. These are the ways to reach them.

The study's own enquiry address

This study publishes an address for enquiries. See it below .
The places running it

86 sites in 16 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Show contact details

Study contacts

Contact

Email: •••••@•••••

Locations

AOU Federico II - Oncologia Clinica
RECRUITING

Naples, 80131, Italy
AdventHealth Medical Group Oncology Research at Celebration
RECRUITING

Kissimmee, Florida, 34747, United States
Aichi Cancer Center Hospital
RECRUITING

Nagoya, 464-8681, Japan
Akershus universitetssykehus
COMPLETED

Lørenskog, 1478, Norway
Amsterdam UMC locatie Vumc
RECRUITING

Amsterdam, 1081 HV, Netherlands
Asan Medical Center
RECRUITING

Seoul, 05505, South Korea
BC Cancer - Vancouver
RECRUITING

Vancouver, V5Z4E6, Canada
Bacs-Kiskun Varmegyei Oktatokorhaz
RECRUITING

Kecskemét, 6000, Hungary
Barts Hospital
RECRUITING

London, EC1A 7BE, United Kingdom
Cancer Institute Hospital of JFCR
RECRUITING

Tokyo, 135-8550, Japan
Centre Georges Franăois Leclerc
RECRUITING

Dijon, 21079, France
Centre Léon Bérard
RECRUITING

Lyon, 69008, France
Centro Ricerche Cliniche di Verona s.r.l.
RECRUITING

Verona, 37134, Italy
Cha Bundang Medical Center, Cha University
RECRUITING

Seongnam, 13496, South Korea
Chang Gung Memorial Hospital
RECRUITING

Taoyuan, 333, Taiwan
Chris O'Brien Lifehouse
RECRUITING

Camperdown, 2050, Australia
Chu Bordeaux
RECRUITING

Bordeaux, 33000, France
Chu Nantes - Hătel Dieu
RECRUITING

Nantes, 44093, France
City of Hope
RECRUITING

Duarte, California, 91010, United States
Cliniques Universitaires Saint-Luc
RECRUITING

Brussels, Belgium
Cross Cancer Institute
RECRUITING

Edmonton, Alberta, T6G 1Z2, Canada
Fred Hutchinson Cancer Center
COMPLETED

Seattle, Washington, 98109, United States
HOSPITAL REGIONAL UNIVERSITARIO de MALAGA AVDA.
RECRUITING

Málaga, 29010, Spain
Haukeland universitetssjukehus
COMPLETED

Lørenskog, 1478, Norway
Health Partners Cancer Center at Regions Hospital
RECRUITING

Saint Paul, Minnesota, 55101, United States
Health Partners Frauenshuh Cancer Center
RECRUITING

Saint Louis Park, Minnesota, 55426, United States
Hopital Claude Huriez - Chu Lille
RECRUITING

Lille, 59000, France
Hospital Clinic de Barcelona
RECRUITING

Barcelona, 08036, Spain
Hospital Clinico Universitario de Valencia
RECRUITING

Valencia, 46010, Spain
Hospital General Universitario Gregorio Marañon
RECRUITING

Madrid, 28009, Spain
Hospital Universitari Vall D'Hebron
RECRUITING

Barcelona, 08035, Spain
Hospital Universitario 12 de Octubre
RECRUITING

Madrid, 28041, Spain
Hospital Universitario Ramon Y Cajal
RECRUITING

Madrid, 28034, Spain
Hospital Universitario Virgen Macarena
RECRUITING

Seville, 41009, Spain
Hospital de La Santa Creu I Sant Pau
RECRUITING

Barcelona, 08041, Spain
Humanitas Gavazzeni
RECRUITING

Bergamo, 24125, Italy
Hăpital de La Timone
RECRUITING

Marseille, 13005, France
ICL - Alexis Vautrin
RECRUITING

Vandœuvre-lès-Nancy, 54500, France
IRCCS Ospedale Policlinico San Martino
RECRUITING

Genova, 16132, Italy
Icon Cancer Centre Chermside
RECRUITING

Chermside, 4032, Australia
Icon Cancer Centre Hobart
RECRUITING

Hobart, 7000, Australia
Icon Cancer Centre Townsville
RECRUITING

Hyde Park, 4812, Australia
Institut Claudius Regaud
RECRUITING

Toulouse, 31100, France
Institut Gustave Roussy
RECRUITING

Villejuif, 94805, France
Johns Hopkins University
RECRUITING

Baltimore, Maryland, 21205, United States
Kanagawa Cancer Center
RECRUITING

Kanagawa, 241-8515, Japan
Kaohsiung Chang Gung Memorial Hospital
RECRUITING

Kaohsiung City, 833, Taiwan
Kindai University Hospital
RECRUITING

Osakasayama-shi, 589-8511, Japan
Koo Foundation Sun Yat-Sen Cancer Center
RECRUITING

Taipei, 11209, Taiwan
Krankenhaus Nordwest GmbH
RECRUITING

Frankfurt, 60488, Germany
Kyungpook National University Chilgok Hospital
RECRUITING

Daegu, 41404, South Korea
Leids Universitair Medisch Centrum
RECRUITING

Leiden, 2333 ZG, Netherlands
Maastricht University Medical Center
RECRUITING

Maastricht, 6229 HX, Netherlands
Memorial Sloan Kettering Hospital
RECRUITING

New York, New York, 10065, United States
Monash Medical Centre Clayton
RECRUITING

Clayton, 3168, Australia
NHO Shikoku Cancer Center
RECRUITING

Matsuyama, 791-0245, Japan
National Cancer Center
RECRUITING

Gyeonggi-do, 410-769, South Korea
National Cancer Center Hospital
RECRUITING

Tokyo, 104-0045, Japan
National Cancer Center Hospital East
RECRUITING

Kashiwa-shi, 277-8577, Japan
National Cheng Kung University Hospital
RECRUITING

Tainan, 704, Taiwan
National Taiwan University Hospital
RECRUITING

Taipei, 100225, Taiwan
Nottingham City Hospital Campus
RECRUITING

Nottingham, NG5 1PB, United Kingdom
Oslo Universitetssykehus HF, Radiumhospitalet
RECRUITING

Oslo, 0379, Norway
Princess Margaret Cancer Centre
COMPLETED

Toronto, M5G2M9, Canada
Radboud University Medical Center
RECRUITING

Nijmegen, 6525 GA, Netherlands
Roswell Park Cancer Institute IDS
RECRUITING

Buffalo, New York, 14203, United States
Royal Free Hospital
RECRUITING

London, NW3 2QG, United Kingdom
SCRI Oncology Partners
RECRUITING

Nashville, Tennessee, 37203, United States
Saitama Medical University International Medical Center
RECRUITING

Hidaka, 350-1298, Japan
Samsung Medical Center
RECRUITING

Seoul, 06351, South Korea
Seoul National University Bundang Hospital
RECRUITING

Seongnam, 13620, South Korea
Seoul National University Hospital
RECRUITING

Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
RECRUITING

Seoul, 03722, South Korea
Shizuoka Cancer Center
RECRUITING

Nagaizumi-cho, 411-8777, Japan
Sun Yat-sen University Cancer Center
RECRUITING

Guangzhou, 510060, China
Sunnybrook Research Institute
RECRUITING

Toronto, M4N 3M5, Canada
Taichung Veterans General Hospital
RECRUITING

Taichung, 407219, Taiwan
Taipei Veterans General Hospital
RECRUITING

Taipei, 11217, Taiwan
The University of Texas MD Anderson Cancer Center
RECRUITING

Houston, Texas, 77030, United States
UZ Leuven
RECRUITING

Leuven, 3000, Belgium
UZA
RECRUITING

Edegem, 2650, Belgium
Universitair Medisch Centrum Groningen
RECRUITING

Groningen, 9713 GZ, Netherlands
Universitair Ziekenhuis Brussel
RECRUITING

Jette, Belgium
Universitair Ziekenhuis Gent
RECRUITING

Ghent, 9000, Belgium
University Hospital Coventry
RECRUITING

Coventry, CV2 2DX, United Kingdom
University of Illinois Cancer Center
RECRUITING

Chicago, Illinois, 60612, United States
Washington University, School of Medicine
RECRUITING

St Louis, Missouri, 63110, United States
West China Hospital, Sichuan University
RECRUITING

Chengdu, 610098, China
Yale Cancer Center
RECRUITING

New Haven, Connecticut, 06510, United States
Yokohama City University Medical Center
RECRUITING

Yokohama, 232-0024, Japan

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