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

NCT04479436 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: U31402-A-U2022019-004418-32
• Study Type: interventional
• Target: 40
• Locations: 8 countries
• Sites: 46

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer; U3-1402

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer

  ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.

  From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Secondary Outcomes (16)

• Duration of Response (DoR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer

  From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

• Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer

  From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

• Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer

  From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

• Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer

  From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

• Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer

  From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

Study Arms (2)

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

EXPERIMENTAL

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

Drug: Patritumab Deruxtecan

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

EXPERIMENTAL

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.

Drug: Patritumab Deruxtecan

Interventions

Patritumab Deruxtecan 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.

Also known as: U3-1402

Cohort 1: HER3 High (IHC 3+, 2+); Cohort 2: HER3 Low/Negative (IHC 1+, 0)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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).

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;

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (46)

Highlands Oncology

Fayetteville, Arkansas, 72703, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern Medical Faculty Foundation NMFF Hematology Oncology

Chicago, Illinois, 60611, United States

Location

John Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Sarah Cannon

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center University of Texas

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Virgina Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Georges-Franois Leclerc

Dijon, 21000, France

Location

CHU Nantes

Nantes, 44000, France

Location

Hospital St Antoine

Paris, 75012, France

Location

Asst Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Aichi Cancer Center Hospital

Nagoya, Nagoya-shi, Aichi-ken, 464-8681, Japan

Location

National Hospital Organization - Osaka National Hospital (ONH)

Osaka, Osaka-shi, Osaka-fu, 540-0006, Japan

Location

Kindai University Hospital

Osaka, Osakasayama Shi, 589-8511, Japan

Location

National Cancer Center Hospital East

Chiba, 277-0023, Japan

Location

The Cancer Institute Hospital Of JFCR

Tokyo, 135-8550, Japan

Location

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

Ostrów Wielkopolski, Poznan, 60-569, Poland

Location

Szpital Kliniczny Przemienienia Pańskiego.University Hospital, Chemotherapy Department

Poznan, Poland

Location

M Sklodowska Curie Memorial Cancer Center

Warsaw, 02-034, Poland

Location

M Sklodowska Curie Memorial Cancer Center

Warsaw, Poland

Location

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

Barcelona, 08003, Spain

Location

VHIO Valle de Hebron Instituto de Oncologia

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario HM Sanchinarro, CIOCC

Madrid, 28050, Spain

Location

Consorci Corporació Sanitària Parc Taulí de Sabadell

Sabadell, 08208, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Royal Marsden Hospital NHS

London, SW3 6JJ, United Kingdom

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

Royal Marsden Hospital NHS

London, United Kingdom

Location

Sarah Cannon

London, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

patritumab deruxtecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo, Inc.

CTRinfo@dsi.com

9089926400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 21, 2020
• Study Start: September 14, 2020
• Primary Completion: February 3, 2022
• Study Completion: February 3, 2022
• Last Updated: May 18, 2025
• Results First Posted: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies 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 from 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 (21); GB (4); IT (1); JP (5); ES (6); PL (4); FR (3); BE (2)