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

Recruiting now · Phase 2

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

In brief

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.

Key facts

Study ID: NCT06172478
Run by: Daiichi Sankyo
People needed: 740
Starts: 2024-02-26
Expected to finish: 2028-10-10
Last updated by the study team: 2026-05-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
Pathologically documented high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
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
Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix.
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
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.
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
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.

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.

Where it is running

Yale Cancer Center — New Haven, Connecticut, United States (enrolling)
AdventHealth Medical Group Oncology Research at Celebration — Kissimmee, Florida, United States (enrolling)
University of Illinois Cancer Center — Chicago, Illinois, United States (enrolling)
Johns Hopkins University — Baltimore, Maryland, United States (enrolling)
Health Partners Frauenshuh Cancer Center — Saint Louis Park, Minnesota, United States (enrolling)
Health Partners Cancer Center at Regions Hospital — Saint Paul, Minnesota, United States (enrolling)
Washington University, School of Medicine — St Louis, Missouri, United States (enrolling)
Roswell Park Cancer Institute IDS — Buffalo, New York, United States (enrolling)
Memorial Sloan Kettering Hospital — New York, New York, United States (enrolling)
SCRI Oncology Partners — Nashville, Tennessee, United States (enrolling)
The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
Fred Hutchinson Cancer Center — Seattle, Washington, United States (enrolling)
Chris O'Brien Lifehouse — Camperdown, Australia (enrolling)
Icon Cancer Centre Chermside — Chermside, Australia (enrolling)
Monash Medical Centre Clayton — Clayton, Australia (enrolling)
Icon Cancer Centre Hobart — Hobart, Australia (enrolling)
Icon Cancer Centre Townsville — Hyde Park, Australia (enrolling)
Cliniques Universitaires Saint-Luc — Brussels, Belgium (enrolling)
UZA — Edegem, Belgium (enrolling)
Universitair Ziekenhuis Gent — Ghent, Belgium (enrolling)
Universitair Ziekenhuis Brussel — Jette, Belgium (enrolling)
UZ Leuven — Leuven, Belgium (enrolling)
Cross Cancer Institute — Edmonton, Alberta, Canada (enrolling)
Sunnybrook Research Institute — Toronto, Canada (enrolling)
City of Hope — Duarte, California, United States (enrolling)

Full record on ClinicalTrials.gov

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