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

NCT ID: NCT04479436

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-14
• Study Completion Date: 2022-02-03

Brief Summary

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.

Detailed Description

There will be 2 cohorts with enrollment in 2 parts. Participants will be treated on Day 1 of each 21-day cycle (every 3 weeks) with U3-1402 5.6 mg/kg intravenous (IV). The estimated treatment period is approximately 8 months and the follow-up period is approximately 4 months.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: HER3 High (IHC 3+, 2+)

Cohort 1 participants will have high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen.

Group Type: EXPERIMENTAL

Patritumab Deruxtecan

Intervention Type: DRUG

U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

Cohort 2: HER3 Low/Negative (IHC 1+, 0)

Cohort 2 participants will have low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels in a pre-treatment biopsy specimen.

Group Type: EXPERIMENTAL

Patritumab Deruxtecan

Intervention Type: DRUG

U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

Interventions

Patritumab Deruxtecan

U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

Intervention Type: DRUG

Other Intervention Names

U3-1402

Eligibility Criteria

Inclusion Criteria

• 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:

1. 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).

2. 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).

3. 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)
• Serum albumin: ≥2.5 g/dL
• Prothrombin time (PT) or PT-international normalized ratio (INR) and activated partial thromboplastin time (aPTT) / partial thromboplastin time (PTT): ≤1.5 × ULN except for subjects on coumarin- derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator

Exclusion Criteria

• 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:

1. any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion)

2. 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:

1. Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;

2. 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;

3. Monoclonal antibodies other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFRs) <28 days;

4. Immune checkpoint inhibitor therapy <21 days;

5. Major surgery (excluding placement of vascular access) <4 weeks;

6. Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days;

7. 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.

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.

2. Participants with a history of hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer).

• Participant with any human immunodeficiency virus (HIV) infection.
• Any evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses, active infection), psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

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

Hospital St Antoine

Paris, , France

Asst Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Aichi Cancer Center Hospital

Nagoya, Nagoya-shi, Aichi-ken, Japan

National Hospital Organization - Osaka National Hospital (ONH)

Osaka, Osaka-shi, Osaka-fu, Japan

Kindai University Hospital

Osaka, Osakasayama Shi, Japan

National Cancer Center Hospital East

Chiba, , Japan

The Cancer Institute Hospital Of JFCR

Tokyo, , Japan

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Ostrów Wielkopolski, Poznan, Poland

Szpital Kliniczny Przemienienia Pańskiego.University Hospital, Chemotherapy Department

Poznan, , Poland

M Sklodowska Curie Memorial Cancer Center

Warsaw, , Poland

M Sklodowska Curie Memorial Cancer Center

Warsaw, , Poland

Hospital del Mar - Institut Hospital del Mar d'Investigacions Mediques IMIM

Barcelona, , Spain

VHIO Valle de Hebron Instituto de Oncologia

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario HM Sanchinarro, CIOCC

Madrid, , Spain

Consorci Corporació Sanitària Parc Taulí de Sabadell

Sabadell, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Royal Marsden Hospital NHS

London, , United Kingdom

Sarah Cannon Research Institute UK

London, , United Kingdom

Royal Marsden Hospital NHS

London, , United Kingdom

Sarah Cannon

London, , United Kingdom

Countries

United States; Belgium; France; Italy; Japan; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2019-004418-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U31402-A-U202

Identifier Type: -

Identifier Source: org_study_id