Safety and Efficacy of INCB007839 With Trastuzumab and Vinorelbine in Patients With Metastatic HER2+ Breast Cancer

Study Overview
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Brief Summary
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This Phase I/II study is designed to assess the safety and therapeutic effect of INCB007839 in combination with trastuzumab and vinorelbine in patients with metastatic HER2+ breast cancer.

Official Title
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A Phase I/II Study to Assess the Safety and Therapeutic Effect of INCB007839 in Combination With Trastuzumab and Vinorelbine in Patients With Metastatic HER2+ Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: INCB007839 300mg BID
* Drug: Trastuzumab
* Drug: Vinorelbine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with diagnosis of metastatic (or locally recurrent-inoperable) breast cancer Subject with histological HER2+ status as determined by FISH with a gene amplification score of ≥ 2.2 Subject with availability of archival biopsy tissue from primary tumor or metastatic lesions Subject with presence of measurable disease based on RECIST 1.1 Subject who has received no more than three prior HER2-directed therapeutic regimens for advanced breast cancer Exclusion Criteria: Subject with Left ventricular ejection fraction (LVEF) below institutional normal range Subject with metastasis to the central nervous system UNLESS asymptomatic and clinically stable Subject with current active malignancy other than breast cancer Subject with prior history of other malignancy except for cancers from which the patient is currently disease free Subject with significant renal or hepatic dysfunction Subject with history of venous or arterial thrombosis or risk factor for thrombosis other than history of malignancy Subject with insufficient bone marrow function Subject with contraindication to vinorelbine, trastuzumab, aspirin and/or warfarin therapy. Subject with current active bacterial, Hepatitis B or C, and/or HIV infections

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A - INCB007839 300mg BID<br>This is a single arm, open label study in which all patients will receive a single dose of the investigational product INCB007839 in combination with a standard regimen of trastuzumab and vinorelbine. | Drug: INCB007839 300mg BID<br>* INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met.<br>Drug: Trastuzumab<br>* INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met.<br>Drug: Vinorelbine<br>* INCB007839 tablets (300 mg BID) in combination with trastuzumab and vinorelbine will be administered in an initial Cycle of 28 days and followed by continuous 21-day cycles subsequently. Trastuzumab will be administered in continuous 21-day cycles beginning on Day 8 of Cycle 1. Vinorelbine will be administered on a weekly schedule for a minimum of the first four cycles beginning on Cycle 1 Day 8. All drugs will be administered continuously as tolerated or until a protocol-defined stopping criteria is met.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety and tolerabilty as determined by monitoring the frequency and severity of adverse events (AEs) and performing clinical assessments and laboratory investigations. |  | Measured monthly starting at Baseline (estimated duration 6-9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall objective response rate assessed by RECIST criteria |  | Measured at Baseline, Cycle 4 and approximately every 9 weeks after (estimated duration 6-9 months) |