Open Label Trial of INCB07839 to Determine Effect and Safety of INCB007839 Plus Trastuzumab in HER2 Positive Metastatic Breast Cancer

Study Overview
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Brief Summary
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This is a single arm, modified dose escalation, open label trial with the objectives of: (1) Determining a safe optimal dose of INCB007839 in combination with trastuzumab and docetaxel (2) Determining clinical efficacy and safety of INCB007839 in combination with trastuzumab and docetaxel.

Official Title
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A Phase 1/2, Modified Dose Escalation, Open Label Trial to Determine the Therapeutic Effect and Safety of INCB007839 Combined With Trastuzumab in Patients With Previously Untreated HER2 Positive Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: INCB007839
* Drug: INCB007839
* Drug: INCB007839
* Drug: INCB007839
* Drug: trastuzumab
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed metastatic breast carcinoma that is HER2 positive Measurable disease as defined by the RECIST criteria Life expectancy greater than or equal to 6 months Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Received any anticancer medications in the 28 days prior to enrollment into this study Received any anticancer medications for cancers other than breast cancer within 6 months prior to enrollment in this study. History of deep venous thrombosis within the last year Contraindication to low dose warfarin therapy Clinically significant cardiomyopathy Prior treatment with INCB007839 or trastuzumab or lapatinib

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A - INCB007839 and Trastuzumab<br>INCB007839 100 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1. | Drug: INCB007839<br>* 100 mg BID<br>Drug: trastuzumab<br>* trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.<br>|
| Experimental: Treatment B - INCB007839 and Trastuzumab<br>INCB007839 200 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1. | Drug: INCB007839<br>* 200 mg BID<br>Drug: trastuzumab<br>* trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.<br>|
| Experimental: Treatment C - INCB007839 and Trastuzumab<br>INCB007839 300 mg BID and trastuzumab In Cycle 1, trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1. | Drug: INCB007839<br>* 300 mg BID<br>Drug: trastuzumab<br>* trastuzumab will be administered at a loading dose of 8 mg/kg as a 90 minute intravenous infusion on Day 8. In all subsequent 21-day cycles, trastuzumab will be administered at 6 mg/kg as a 90 minute intravenous infusion on Day 1.<br>|
| Experimental: Treatment D - INCB007839 and Docetaxel<br>INCB007839 300mg BID with docetaxel | Drug: INCB007839<br>* 300 mg BID<br>Drug: Docetaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (complete + partial response) using RECIST (Response Evaluation Criteria in Solid Tumor) criteria |  | Day 1 of each completed subsequent 21-day treatment cycle and the End of Study Visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the plasma pharmacokinetic (PK) profile of INCB007839 and trastuzumab when given in combination | For Cycle 1, PK samples to be collected on Day 8 and Day 15 at pre-dose the morning dose of INCB007839. For Cycles 2, 3 and 4, PK will be collected as a single sample, obtained at pre-dose, on Day 1. PK samples will not be collected at Cycle 5 or later. o. For Cycle 1, PD samples to be collected at time of screening and at pre-dose on Day 1, Day | Monthly |