Safety Study of the Drug MM-151 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

• Number of dose limiting toxicities (DLTs) within a cohort [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Adverse event profile of MM-151 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Objective response to MM-151 based on RECIST [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• Number of dose limiting toxicities (DLTs) within a cohort [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Adverse event profile of MM-151 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• To describe any objective response to MM-151 based on RECIST [ Time Frame: 2 years ] [ Designated as safety issue: No ]

This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design, evaluating MM-151 at varying dose levels and frequencies.

This study is a Phase 1 and pharmacologic open-labeled 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. The study will explore a weekly dosing schedule, an every other week dosing schedule and an every three week dosing schedule. An Expansion Cohort will be enrolled following demonstration of safety and adequate MM-151 concentration levels in the dose escalation phase. The expansion cohort will further characterize safety, pharmacokinetics and explore pharmacodynamic endpoints. It is expected that approximately 4 study sites will participate.

• Experimental: MM-151 Weekly Dosing
  Dose escalation frequency - once weekly
  Intervention: Drug: MM-151
• Experimental: MM-151 Every Other Week Dosing
  Dose escalation frequency - every other week
  Intervention: Drug: MM-151
• Experimental: MM-151 Every Three Week Dosing
  Dose escalation frequency - every three weeks
  Intervention: Drug: MM-151

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed advanced malignant solid tumor that has recurred or progressed following standard therapy, or that has not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
• Patients must be > 18 years of age
• Patients of their legal representatives must be able to understand and sign an informed consent form
• Patients must have evaluable or measurable tumor(s)
• Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy
• Women of childbearing potential as well as fertile men and their partners must agree 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-151 (an effective form of contraception is an oral contraceptive or a double barrier method)

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 > 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 CNS malignancies (primary or metastatic); 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