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

Metastatic Breast Cancer Clinical Trial

Official title:

Phase 1/2, Multicenter, Open-label, Multiple-Dose First-in-human Study of U3-1402, in Subjects With HER3 Positive Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02980341
• Other study ID #: U31402-A-J101
• Secondary ID: JapicCTI-163401
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 28, 2016
• Est. completion date: September 7, 2023

Study information

• Verified date: December 2023
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: September 7, 2023
• Est. primary completion date: August 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Is 18 Years and older in the United States or 20 Years and older in Japan

2. Has a pathologically documented advanced/unresectable or metastatic breast cancer

3. Documented HER3-positive disease measured by immunohistochemistry (IHC)

4. Has disease that is refractory to or intolerable with standard treatment, or for which standard treatment no longer is available

5. Has an Eastern Cooperative Oncology Group Performance Status 0-1

6. Has Left Ventricular Ejection Fraction = 50%

7. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Additional Inclusion Criteria for Dose Finding Part and Dose Expansion Part:

8. Has received 2-6 prior chemotherapy regimens for breast cancer, at least 2 of which were administered for treatment of advanced/unresectable or metastatic disease. At least 1 prior chemotherapeutic regimen must have included a taxane, administered in the neoadjuvant, adjuvant, or advanced setting. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)

Additional Inclusion Criteria for Dose Expansion Part Only:

9. Is able to submit a fresh tumor biopsy sample prior to starting study treatment if not already submitted for HER3 expression

10. Has documented hormone (estrogen and/or progesterone) receptor (HR)-positive and HER2 negative expression according to American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines. (With exception of Dose Expansion Part TNBC cohort. See additional inclusion criteria for Dose Expansion Part TNBC cohort.)

Additional Inclusion Criteria for Dose Expansion Part TNBC cohort Only:

11. 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

12. Has progressed after receiving 1 to 2 prior chemotherapy regimens for advanced/unresectable or metastatic breast cancer.

Exclusion Criteria:

1. Prior treatment with a HER3 antibody

2. Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)

3. Has a medical history of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment

4. Has a medical history of myocardial infarction or unstable angina

5. Has a corrected QT prolongation to > 450 millisecond (ms) in males and > 470 ms in females

6. 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

7. Has clinically significant corneal disease

Additional Exclusion Criteria for Dose Expansion Part:

8. Prior treatment with an govitecan derivative (eg, IMMU-132).

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

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

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East	Chiba
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Local Independent Administrative Corporation Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital	Hiroshima
Japan	Hakuaikai Social Medical Corporation Sagara Hospital	Kagoshima
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kumamoto University Hospital	Kumamoto
Japan	Aichi Cancer Center Hospital	Nagoya
Japan	Nagoya City University Hospital	Nagoya
Japan	Kindai University Hospital	Osaka
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Saitama Cancer Center	Saitama
Japan	Saitama Medical University International Medical Center	Saitama
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo-Shi	Hokkaido
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Tokyo
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Northwestern University	Chicago	Illinois
United States	Texas Oncology, P.A.	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Southeastern Regional Medical Center	Newnan	Georgia
United States	Mays Cancer Center	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.	Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants experiencing adverse events (AEs)	AEs will be collected systematically from signing of the informed consent form (ICF) through 28 days after last dose	within about 6 months
Primary	Number of participants with tumor response throughout the study using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1		From screening until disease progresses, within about 6 months
Secondary	Dose Escalation Part: Area under the serum concentration time curve (AUC) of U3-1402	Samples are obtained for all secondary outcome measures in the Dose Escalation Part at Cycle 1: Days 1, 2, 4, 8, 15; Cycle 2: Days 1, 8, 15; Cycle 3: Days 1, 2, 4, 8, 15; Cycles 4, 6, 8: Day 1	Cycle 1, Day 1 to Cycle 8, Day 1 (148 days)
Secondary	Dose Finding Part: AUC of U3-1402	Samples are obtained for all secondary outcome measures in the Dose Finding Part for the following categories: Cohorts 1 and 2: at Cycle 1: Days 1, 2, 4, 8, 15; Cycle 2: Day 1; Cycle 3: Days 1, 8, 15; Cycles 4, 5, 6, 8: Day 1; Cohort 3: at Cycles 1, 2, 3: Days 1, 8, 15; Cycles 4, 5, 6, 8: Day 1; Cohorts 4 and 5: at Cycle 1: Days 1, 4, 8; Cycle 2: Day 1; Cycle 3: Days 1, 4, 8; Cycle 4: Days 1, 8, 15; Cycles 5, 6, 8: Day 1	Cycle 1, Day 1 to Cycle 8, Day 1 (148 days)
Secondary	Dose Expansion Part: AUC of U3-1402	Samples are obtained for all secondary outcome measures in the Dose Expansion Part at Cycle 1, Days 1, 2, 4, 8, 15; Cycle 2, Day 1; Cycle 3, Days 1, 8, 15; Cycles 4, 6, 8; Day 1	Cycle 1, Day 1 to Cycle 8, Day 1 (148 days)
Secondary	Dose Escalation Part: Maximum plasma concentration (Cmax) of U3-1402		within 148 days
Secondary	Dose Finding Part: Cmax of U3-1402		within 148 days
Secondary	Dose Expansion Part: Cmax of U3-1402		within 148 days
Secondary	Dose Escalation Part: Time to maximum plasma concentration (Tmax) of U3-1402		within 148 days
Secondary	Dose Finding Part: Tmax of U3-1402		within 148 days
Secondary	Dose Expansion Part: Tmax of U3-1402		within 148 days
Secondary	Dose Escalation Part: Change in Total anti-HER3 antibody from U3-1402		Baseline, 6 months
Secondary	Dose Finding Part: Change in Total anti-HER3 antibody from U3-1402		Baseline, 6 months
Secondary	Dose Expansion Part: Change in Total anti-HER3 antibody from U3-1402		Baseline, 6 months
Secondary	Dose Escalation Part: Change in MAAA-1181 level from U3-1402		within 148 days
Secondary	Dose Finding Part: Change in MAAA-1181 level from U3-1402		within 148 days
Secondary	Dose Expansion Part: Change in MAAA-1181 level from U3-1402		within 148 days