A Five-Tier, Open-Label Study of IMC-A12 in Advanced Sarcoma

A Five-Tier, Phase 2 Open-Label Study of IMC-A12 Administered as a Single Agent Every 2 Weeks in Patients With Previously-Treated, Advanced or Metastatic Soft Tissue and Ewing's Sarcoma/PNET

This multicenter study will enroll approximately 185 participants with metastatic or advanced sarcoma, to assess the effectiveness and safety of IMC-A12 monotherapy for this indication. Participants will be stratified into five tiers according to diagnosis:

1. Ewing's sarcoma/peripheral neuroectodermal tumor (PNET)
2. rhabdomyosarcoma
3. leiomyosarcoma
4. adipocytic sarcoma
5. synovial sarcoma.

A total of 85 participants will be enrolled initially, 17 in each tier. Participants will receive single agent IMC-A12 every 2 weeks. A treatment cycle will be defined as 6 weeks, with radiological evaluation at every cycle.

Safety and response in the initial 17 participants in each tier will be used to determine whether to extend enrollment to the target total of 37 participants per tier.

The purpose of this study is to determine the progression-free survival (PFS) rate assessed 12 weeks after the initiation of IMC-A12 monotherapy, administered every 2 weeks to participants with previously-treated, advanced or metastatic soft tissue and Ewing's sarcoma/PNET.

Inclusion:

• Histologically or cytologically-confirmed sarcoma of one of the following histologies: (1) Ewing's sarcoma / PNET; (2) rhabdomyosarcoma; (3) leiomyosarcoma; (4) adipocytic sarcoma; or (5) synovial sarcoma
• Has measurable disease, at least one lesion ≥ 2 centimeters (cm) on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
• Has at least one measurable lesion located outside of a previously irradiated area
• Has radiographic documentation of disease progression within 6 months prior to study entry
• Has relapsed, refractory, and/or metastatic disease, incurable by surgery, radiotherapy, or other conventional systemic therapy
• Been considered ineligible for systemic chemotherapy or received at least one previous regimen for relapsed, refractory, and/or metastatic disease
• Adequate hematologic function
• Has adequate hepatic function
• Has adequate coagulation function
• Has adequate renal function
• Has fasting serum glucose < 120 milligrams per deciliter (mg/dL) or below the upper limit of normal (ULN)
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

Exclusion:

• Has uncontrolled brain or leptomeningeal metastases
• Not recovered to grade ≤ 1 from adverse events due to agents administered more than 3 weeks prior to study entry
• Is receiving any other investigational agent(s)
• Major surgery, hormonal therapy (other than replacement), chemotherapy, radiotherapy, or any form of investigational therapy within 3 weeks prior to enrollment
• History of treatment with other agents targeting the insulin-like growth factor-I receptor (IGF-IR)
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to that of IMC-A12
• Has poorly controlled diabetes mellitus
• Is receiving therapy with immunosuppressive agents
• Is pregnant or breastfeeding