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

• 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) [ Time Frame: December 2011 ] [ Designated as safety issue: No ]
• To explore the role functional imagining (FDG-PET CT Scan), as a predictor of clinical activity [ Time Frame: December 2011 ] [ Designated as safety issue: No ]

This study is an open-label Phase 1 trial of MM-111.

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

• Her2 Amplified Solid Tumors
• Metastatic Breast Cancer

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)