QUILT-3.026: AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors

Study Overview
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Brief Summary
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This is a multi-center, 2-part phase 1b/2 study of AMG 655 in combination with AMG 479 to be conducted in the United States and Spain. Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerable. Part 2 will evaluate the safety and estimate the efficacy of AMG 655 at the dose selected in Part 1 in combination with AMG 479 for the treatment of patients with advanced NSCLC (non-squamous histology; squamous histology), CRC, pancreatic cancer, ovarian cancer, and sarcoma.

Official Title
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A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination With AMG 479 in Subjects With Advanced, Refractory Solid Tumors

Conditions
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Colorectal Cancer, Locally Advanced, Metastatic Cancer, Non-Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Sarcoma, Solid Tumors

Intervention / Treatment
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* Biological: AMG 479
* Biological: AMG 655


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: Histologically or cytologically confirmed, locally advanced or metastatic, treatment-refractory solid tumors Part 2: Histologically or cytologically confirmed, locally advanced or metastatic: NSCLC (squamous or non-squamous cell carcinoma; up to 2 prior treatment regimens), Colorectal Cancer (up to 2 prior treatment regimens), Pancreatic Cancer (up to 1 prior treatment regimen), Ovarian cancer (up to 2 prior treatment regimens), or Sarcoma (up to 2 prior treatment regimens), according to cohort availability Eastern Cooperative Group (ECOG performance status of 0 or 1 Women or men ≥16 years of age Adequate hematology, renal, hepatic, coagulation and glycemic function. Exclusion Criteria: Presence of uncontrolled central nervous system (CNS) disease Systemic chemotherapy, hormonal therapy, immunotherapy, experimental or approved anticancer proteins/antibodies therapy ≤28 days before enrollment. Prior treatment with death receptor agonists (including but not limited to rhApo2L/TRAIL [AMG951], apomab, mapatumumab, lexatumumab, CS-1008) Prior treatment with IGF receptor antagonists (including but not limited to CP-751, 871, MK0646, AVE1642 or IMC-A12)

Ages Eligible for Study
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Minimum Age: 16 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Cohort 3<br>AMG 479 18 mg/kg IV plus AMG 655 15 mg/kg IV (day 1 of each Q3W cycle) | Biological: AMG 479<br>* AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.<br>Biological: AMG 655<br>* AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5.<br>* Other names: AMG 655 is also known as conatumumab.;|
| Experimental: Part 1 Cohort 1<br>AMG 479 18 mg/kg IV plus AMG 655 1 mg/kg IV (day 1 of each Q3W cycle) | Biological: AMG 479<br>* AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.<br>Biological: AMG 655<br>* AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5.<br>* Other names: AMG 655 is also known as conatumumab.;|
| Experimental: Part 1 Cohort 2<br>AMG 479 18 mg/kg IV plus AMG 655 3 mg/kg IV (day 1 of each Q3W cycle) | Biological: AMG 479<br>* AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.<br>Biological: AMG 655<br>* AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5.<br>* Other names: AMG 655 is also known as conatumumab.;|
| Experimental: Part 2<br>AMG 479 18 mg/kg IV plus AMG 655 15 mg/kg Q3W, or the MTD, as determined in Part 1 of the study | Biological: AMG 479<br>* AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.<br>Biological: AMG 655<br>* AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5.<br>* Other names: AMG 655 is also known as conatumumab.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incedence of dose limiting toxicity |  | Length of Study | 
| Objective response rate |  | Length of Study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response |  | Length of Study | 
| Duration of response |  | Length of Study | 
| Progression free survival |  | Length of Study | 
| To evaluate anti-AMG 655 antibody formation and anti-AMG 479 antibody formation |  | Length of Study | 
| To evaluate the PK of AMG 655 and of AMG 479 |  | Length of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 655, AMG 479, Apoptosis, Monoclonal Antibody, Tumor Necrosis Factor, Insulin-like Growth Factor