A Study of MM-111 in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Cancers

Study Overview
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Brief Summary
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This study is an open-label Phase 1 trial of MM-111.

Detailed Description
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Phase 1: Patients with any solid tumor type may be enrolled to evaluate the safety and tolerability of MM-111.

Official Title
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A Phase 1 and Pharmacologic Study of MM-111 in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Cancers

Conditions
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Her2 Amplified Solid Tumors, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: MM-111


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed advanced cancer that is: HER2 amplified (IHC 2+ or greater) based on archived tumor evaluation Heregulin positive based on a study required fresh biopsy sample performed at screening and confirmed by central laboratory Patients must have blocks of archived formalin-fixed, paraffin-embedded tumor tissue available for sectioning and immunohistochemical staining Patient's cancer must have recurred or progressed following standard therapy, have not responded to standard therapy, or for which no standard therapy exists. Patients must be >= 18 years of age Patients or their legal representatives must be able to understand and sign an informed consent Patients may have measurable or non-measurable tumor(s) Patients should have ECOG Performance Score (PS) 0 or 1 Patients must have adequate bone marrow reserves as evidenced by: Absolute neutrophil count (ANC) >= 1,500/uL and Platelet count >= 100,000/uL Hemoglobin >= 9 g/dL Patients must have tumor tissue amenable to biopsy Patients must be willing to undergo biopsy prior to treatment to MM-111 Exclusion Criteria: Patients for whom potentially curative antineoplastic therapy is available Patients who are pregnant or lactating Patients with an active infection or with an unexplained fever greater than 38.5 C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled) Patients with untreated and/or symptomatic primary or metastatic CNS malignancies (patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies (patients with a history of hypersensitivity to trastuzumab, a humanized antibody, are not excluded) Patients with known HIV, hepatitis B or C (if patients have previously been treated for C and have undetectable viral loads, they can be considered eligible for the trial)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MM-111<br> | Drug: MM-111<br>* For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) or Maximum Feasible Dose | The Maximum Tolerated Dose (MTD) was defined as the highest dose level in which a DLT is experienced by fewer than two patients in a cohort of 3 - 6 patients. If a DLT is observed in at least two patients in a cohort of 3 - 6 patients, the MTD will be determined to have been exceeded and an additional three patients (up to a total of six) are to be treated at the next lower dose level. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine the Clinical Activity of MM-111 in Patients Based on Objective Response Rate (ORR), Duration of Response (DoR), Progression Free Survival (PFS), and 16 & 24-week Clinical Benefit Rate (CBR) |  | December 2011 | 
| To Explore the Role Functional Imagining (FDG-PET CT Scan), as a Predictor of Clinical Activity |  | December 2011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Her2 amplified solid tumors, Breast Cancer, Her3/ErbB3, Bispecific Antibody