A Study to Evaluate U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer

Stopped early · Phase 2

Conditions studied: Metastatic Colorectal Cancer

In brief

This study is designed to primarily evaluate the safety and efficacy of U3-1402 in participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2 prior lines of therapy and will explore clinical benefit according to human epidermal growth factor receptor 3 (HER3) tumor expression level in otherwise refractory tumors.

Key facts

Study ID

NCT04479436

Run by

Daiichi Sankyo

People needed

40

Starts

2020-09-14

Expected to finish

2022-02-03

Last updated by the study team

2025-05-18

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participant has provided written informed consent prior to the start of any study specific procedures.
• Participants ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
• Pathological/histological confirmation of advanced or metastatic colon or rectal adenocarcinoma.
• Must be resistant, refractory, or intolerant to at least 2 prior lines of systemic therapy, that must include all of the following agents:
• Fluoropyrimidine
• Irinotecan
• Platinum agents (e.g, oxaliplatin)
• An anti-epidermal growth factor receptor (EGFR) agent, if clinically indicated
• An anti-VEGF agent, if clinically indicated (eg, bevacizumab)
• An immune checkpoint inhibitor (eg, microsatellite instability-high [MSI-H] status)
• A BRAF inhibitor, if clinically indicated (eg, BRAF V600E positive)
• Has at least 1 measurable lesion confirmed by blinded independent central review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1.
• Willing to provide a required pre-treatment tumor biopsy and an additional archival tissue sample for the assessment of HER3 expression levels by immunohistochemistry and exploratory biomarkers, defined as:
• Pre-treatment tumor biopsy. Participants may be exempted from the requirement to provide a pre-treatment tumor biopsy if archival tumor tissue was collected within 3 months of screening during or after treatment with the last prior cancer treatment and is of sufficient quantity (2 cores or 20 slides with adequate tumor tissue content).
• An additional archival tissue sample collected greater than 3 months prior to screening must be available and of sufficient quantity, as defined above, at the time of screening. If an archival tissue sample (collected greater than 3 months prior to screening) is not available, a subject may be included provided the pre-treatment tumor biopsy is obtained and after discussion and agreement from Sponsor (Medical Monitor or designee).
• Consent to provide on-treatment tumor biopsy. When at least 10 treatment tumor biopsies have been collected, the Sponsor will provide written notification of a change to the requirement.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Life expectancy ≥3 months.
• Has adequate bone marrow reserve and organ function at baseline based on local laboratory data defined as follows within 14 days prior to Cycle 1 Day 1:
• Platelet count: ≥100,000/mm\^3 or ≥100 × 10\^9/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)
• Hemoglobin: ≥9.0 g/dL (transfusion and/or growth factor support is allowed)
• Absolute neutrophil count: ≥1500/mm\^3 or ≥1.5 × 10\^9/L
• Serum creatinine (SCr) OR creatinine clearance (CrCl): SCr ≤ 1.5 × upper limit of normal (ULN), OR CrCl ≥ 30 mL/min as calculated using the Cockcroft- Gault equation or measured CrCl; confirmation of CrCl is only required when creatinine is >1.5 × ULN
• Alanine aminotransferase /aspartate aminotransferase: ≤3 × ULN (if liver metastases are present, ≤5 × ULN)
• Total bilirubin: ≤1.5 × ULN if no liver metastases (<3 × ULN in the presence of documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases)

You may not qualify if…

• Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
• Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
• any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion)
• any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)
• OR prior complete pneumonectomy.
• Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone 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.
• Evidence of leptomeningeal disease.
• Evidence of clinically active spinal cord compression or brain metastases
• Inadequate washout period prior to Cycle 1 Day 1 of U3-1402:
• Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;
• Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study <14 days or 5 half-lives, whichever is longer;
• Monoclonal antibodies other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFRs) <28 days;
• Immune checkpoint inhibitor therapy <21 days;
• Major surgery (excluding placement of vascular access) <4 weeks;
• Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days;
• Chloroquine/hydroxychloroquine ≤14 days.
• Prior treatment with an anti-HER3 antibody and/or antibody drug conjugate (ADC) that consists of an exatecan derivative that is any topoisomerase I inhibitor (e.g, trastuzumab deruxtecan).
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≤1 or baseline.
• Had primary malignancies other than CRC within 3 years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
• Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1.
• Known Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1.
• Participants with past or resolved hepatitis B virus (HBV) infection are eligible if:
• Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR
• HBsAg positive and HBV deoxyribonucleic acid (DNA) viral load is documented to be ≤2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases values (in the absence of liver metastasis); OR
• HBsAg positive and HBV DNA viral load is documented to be ≤2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation for participants with liver metastasis and abnormal transaminases with a result of AST/ALT <3 × ULN.

Where it is running

• Highlands Oncology — Fayetteville, Arkansas, United States
• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• University of Colorado Hospital — Aurora, Colorado, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Emory University — Atlanta, Georgia, United States
• Northwestern Medical Faculty Foundation NMFF Hematology Oncology — Chicago, Illinois, United States
• John Hopkins Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States
• Henry Ford Health System — Detroit, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Washington University — St Louis, Missouri, United States
• Nebraska Cancer Specialists — Omaha, Nebraska, United States
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• West Cancer Center — Germantown, Tennessee, United States
• Sarah Cannon — Nashville, Tennessee, United States
• Mary Crowley Cancer Research — Dallas, Texas, United States
• University of Texas Southwestern Medical Center — Dallas, Texas, United States
• MD Anderson Cancer Center University of Texas — Houston, Texas, United States
• Utah Cancer Specialists — Salt Lake City, Utah, United States
• Virgina Cancer Specialists — Fairfax, Virginia, United States
• UZ Antwerpen — Edegem, Belgium
• UZ Leuven — Leuven, Belgium
• Centre Georges-Franois Leclerc — Dijon, France
• CHU Nantes — Nantes, France

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.