Phase I/II Study of U3-1402 in Subjects With Human Epidermal Growth Factor Receptor 3 (HER3) Positive Metastatic Breast Cancer

NCT02980341 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: U31402-A-J101JapicCTI-163401
• Study Type: interventional
• Target: 182
• Locations: 2 countries
• Sites: 26

Brief Summary

This is an open-label, three-part, multiple-dose study to evaluate safety, tolerability, and efficacy of U3-1402 in patients with HER3-positive metastatic breast cancer. HER3 is a unique member of the human epidermal growth factor receptor, which defines a certain type of cancer. The number of patients and treatment cycles are not fixed in this study. Subjects who continue to derive clinical benefit from the study treatment in the absence of withdrawal of consent, progressive disease (PD), unacceptable toxicity, or death may continue the study treatment until the end of the trial.

Conditions

Metastatic Breast Cancer

Keywords

Oncology; HER3; Antibody drug conjugate; Developmental Phase I/II

Outcome Measures

Primary Outcomes (2)

• Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)

  AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose

  Baseline up to 28 days post last dose, up to approximately 9 months

• Number of Participants With Best Overall Tumor Response Using Blinded Independent Central Review Based on Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

  CR was defined as a disappearance of all target and non-target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target and non-target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target and non-target lesions. Objective response rate is the number of patients with confirmed complete response and confirmed partial response.

  From screening until disease progresses, up to approximately 9 months

Secondary Outcomes (18)

• Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd

  Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

• Dose Finding Part: AUC of Anti-HER3-ac-DXd

  Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

• Dose Expansion Part: AUC of Anti-HER3-ac-DXd

  Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

• Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd

  Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)

• Dose Finding Part: Cmax of Anti-HER3-ac-DXd

  Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)

Study Arms (3)

Dose Escalation Part

EXPERIMENTAL

Participants receive U3-1402 from 1.6 mg/kg to 8.0 mg/kg, administered via intravenous (IV) solution at 3-week intervals.

Drug: Patritumab Deruxtecan

Dose Finding Part

EXPERIMENTAL

Participants receive 1 of 5 different U3-1402 dosing regimens, administered via IV solution at 2 or 3-week intervals at doses at or lower than those studied in the Dose Escalation Part.

Drug: Patritumab Deruxtecan

Dose Expansion Part

EXPERIMENTAL

Participants with HER3 high, HER2 negative, HR positive status receive 4.8 mg/kg or 6.4 mg/kg of U3-1402 administered via intravenous (IV) solution at 3-week intervals. Participants with HER3 low, HER2 negative, HR positive status receive 6.4 mg/kg of U3-1402 administered via intravenous (IV) solution at 3-week intervals. Participants with HER3 high, HER2 negative, HR negative status receive 6.4 mg/kg of U3-1402 administration via intravenous (IV) solution at 3-week intervals.

Drug: Patritumab Deruxtecan

Interventions

Patritumab Deruxtecan DRUG

U3-1402 consists of an antibody component (patritumab, U3-1287) covalently conjugated to a drug-linker (MAAA-1162a) containing a drug component (MAAA-1181a)

Also known as: U3-1402

Dose Escalation Part; Dose Expansion Part; Dose Finding Part

Eligibility Criteria

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

You may qualify if:

• Is 18 Years and older in the United States or 20 Years and older in Japan
• Has a pathologically documented advanced/unresectable or metastatic breast cancer
• Documented HER3-positive disease measured by immunohistochemistry (IHC)
• Has disease that is refractory to or intolerable with standard treatment, or for which standard treatment no longer is available
• Has an Eastern Cooperative Oncology Group Performance Status 0-1
• Has Left Ventricular Ejection Fraction ≥ 50%
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression
• Has documented hormone (estrogen and progesterone) receptor (HR)-negative and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines
• Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer.

You may not qualify if:

• Prior treatment with a HER3 antibody
• Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)
• Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment
• Has a medical history of myocardial infarction or unstable angina
• Has a corrected QT prolongation to \> 450 millisecond (ms) in males and \> 470 ms in females
• Has a medical history of clinically significant lung diseases (eg, interstitial pneumonia, pneumonitis, pulmonary fibrosis, and radiation pneumonitis) or who are suspected to have these diseases by imaging at screening period
• Has clinically significant corneal disease
• Prior treatment with an govitecan derivative (eg, IMMU-132).

Sponsors & Collaborators

• Daiichi Sankyo Co., Ltd.: lead
• Daiichi Sankyo: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (26)

Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10022, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75231, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Fukushima Medical University Hospital

Fukushima, 960-1295, Japan

Location

Local Independent Administrative Corporation Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital

Hiroshima, 730-518, Japan

Location

Hakuaikai Social Medical Corporation Sagara Hospital

Kagoshima, 892-0833, Japan

Location

Kanagawa Cancer Center

Kanagawa, 241-0815, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Aichi Cancer Center Hospital

Nagoya, 464-8681, Japan

Location

Nagoya City University Hospital

Nagoya, 467-8602, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, 540-0006, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Kindai University Hospital

Osaka, 589-8511, Japan

Location

Saitama Medical University International Medical Center

Saitama, 350-1298, Japan

Location

Saitama Cancer Center

Saitama, 362 0806, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Tokyo, 135-8550, Japan

Location

Related Publications (1)

• Krop IE, Masuda N, Mukohara T, Takahashi S, Nakayama T, Inoue K, Iwata H, Yamamoto Y, Alvarez RH, Toyama T, Takahashi M, Osaki A, Saji S, Sagara Y, O'Shaughnessy J, Ohwada S, Koyama K, Inoue T, Li L, Patel P, Mostillo J, Tanaka Y, Sternberg DW, Sellami D, Yonemori K. Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. J Clin Oncol. 2023 Dec 20;41(36):5550-5560. doi: 10.1200/JCO.23.00882. Epub 2023 Oct 6.

  PMID: 37801674 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

patritumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

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 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: December 2, 2016
• Study Start: November 28, 2016
• Primary Completion: August 16, 2021
• Study Completion: September 7, 2023
• Last Updated: October 30, 2024
• Results First Posted: August 13, 2024

Record last verified: 2024-10

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 (10); JP (16)