Clinical trial NCT02980341: Phase I/II Study of U3-1402 in Subjects With Human Epidermal Growth Factor Receptor 3 (HER3) Positive Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Oncology
HER3
Antibody drug conjugate
Developmental Phase I/II
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
name: Merck Sharp & Dohme LLC
First posted: 2016-12-02
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Key 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).

Primary outcomes:
measure: Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 28 days post last dose, up to approximately 9 months
measure: 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
timeFrame: From screening until disease progresses, up to approximately 9 months
Secondary outcomes:
measure: Dose Escalation Part: Area Under the Serum Concentration Time Curve (AUC) of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Finding Part: AUC of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
measure: Dose Expansion Part: AUC of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Escalation Part: Maximum Plasma Concentration (Cmax) of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Finding Part: Cmax of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
measure: Dose Expansion Part: Cmax of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Escalation Part: Time to Maximum Plasma Concentration (Tmax) of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Finding Part: Tmax of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
measure: Dose Expansion Part: Tmax of Anti-HER3-ac-DXd
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Escalation Part: Area Under the Concentration-Time Curve of Total Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Finding Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
measure: Dose Expansion Part: Area Under the Concentration-Time Curve in Total Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Escalation Part: Cmax of Total Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Finding Part: Cmax of Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
measure: Dose Expansion Part: Cmax in Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Escalation Part: Tmax of Total Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
measure: Dose Finding Part: Tmax of Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 4, Day 21 (each cycle is 21 days)
measure: Dose Expansion Part: Tmax in Anti-HER3 Antibody
timeFrame: Cycle 1, Day 1 to Cycle 3, Day 21 (each cycle is 21 days)
Other outcomes:
Locations:
city: Newnan
country: United States
facility: Southeastern Regional Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Center
state: Texas
city: Sapporo-Shi
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Hiroshima
country: Japan
facility: Local Independent Administrative Corporation Hiroshima City Hospital Organization Hiroshima City Hiroshima Citizens Hospital
city: Kagoshima
country: Japan
facility: Hakuaikai Social Medical Corporation Sagara Hospital
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Saitama
country: Japan
facility: Saitama Medical University International Medical Center
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: