Safety and Pharmacokinetic Study of MM-302 in Patients With Advanced Breast Cancer

Study Overview
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Brief Summary
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This study is a Phase 1 and pharmacologic open-label dose-escalation trial using a 3+3 design. Successive cohorts of three or more patients will be treated at escalating doses until a maximum tolerated dose is identified. Once the maximum tolerated dose is identified, an Expansion Cohort will be enrolled at that dose to further characterize safety and pharmacologic endpoints. Additional arms will be enrolled to explore the combination of MM-302 with trastuzumab or trastuzumab plus cyclophosphamide in patients with advanced HER2 positive breast cancer.

Official Title
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A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, and Pharmacokinetic Clinical Study of Intravenously Administered MM-302 Monotherapy and in Combination With Trastuzumab With or Without Cyclophosphamide in Patients With Advanced HER2 Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: MM-302 Monotherapy
* Drug: MM-302 in combination with trastuzumab
* Drug: MM-302 in combination with trastuzumab q3w
* Drug: MM-302 in combination with trastuzumab and cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced/unresectable or metastatic breast cancer Eighteen years of age or above Able to understand and sign an informed consent (or have a legal representative who is able to do so) Measurable disease according to RECIST v1.1 ECOG Performance Score of 0 or 1 Adequate bone marrow, hepatic, renal and cardiac function Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-302 Exclusion Criteria: Patients for whom potentially curative anticancer therapy is available Active infection or fever > 38.5°C during screening visits or on the first scheduled day of dosing Symptomatic CNS disease Known hypersensitivity to any of the components of MM-302 or who have had hypersensitivity reactions to fully human monoclonal antibodies Received other recent antitumor therapy Pregnant or breast feeding Patients with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: MM-302<br> | Drug: MM-302 Monotherapy<br>* Escalating doses of MM-302 as a single agent<br>|
| Experimental: MM-302 in Combination with Trastuzumab<br> | Drug: MM-302 in combination with trastuzumab<br>* Escalating MM-302 at an every 4 week dosing schedule, while the dose of trastuzumab is fixed at an every 2 week dosing schedule<br>* Other names: Herceptin;|
| Experimental: MM-302 in Combination with Trastuzumab q3w<br> | Drug: MM-302 in combination with trastuzumab q3w<br>* Escalating MM-302 at an every 3 week dosing schedule, while the dose of trastuzumab is fixed at an every 3 week dosing schedule<br>* Other names: herceptin;|
| Experimental: MM-302 in Combination with Trastuzumab and Cyclophosphamide<br> | Drug: MM-302 in combination with trastuzumab and cyclophosphamide<br>* Escalating MM-302 at an every 3 week dosing schedule, while the dose of trastuzumab and cyclophosphamide is fixed at an every 3 week dosing schedule<br>* Other names: cytoxan; neosar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The severity and the number of adverse events related to escalating doses of the MM-302. |  | 12 months | 
| The severity and the number of adverse events related to escalating doses of the MM-302 in combination with trastuzumab with or without cyclophosphamide |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate of MM-302 |  | 12 months | 
| The pharmacokinetics of MM-302 as determined by measuring AUC, Tmax and Cmax |  | 12 months | 
| Immunogenicity of MM-302 by confirming whether MM-302 elicits an immune response or not |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MM302, Breast Cancer, Locally advanced/unresectable, metastatic