Open Label Extension Study of Conatumumab and Ganitumab (AMG 479)

Study Overview
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Brief Summary
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The purpose of this protocol is to allow continued treatment with conatumumab and/or ganitumab, with or without chemotherapy, to participants who completed a separate Amgen-sponsored conatumumab or ganitumab study without disease progression whose previous studies were closed.

Official Title
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A Phase 2 Open Label Extension Study of Conatumumab and AMG 479

Conditions
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Advanced Solid Tumors, Carcinoid, Colorectal Cancer, Locally Advanced, Lymphoma, Metastatic Cancer, Non-Small Cell Lung Cancer, Sarcoma, Solid Tumors

Intervention / Treatment
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* Drug: Modified FOLFOX6
* Biological: Conatumumab
* Biological: Ganitumab
* Biological: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be enrolled in this study, subjects must be currently enrolled in a prior Amgen-sponsored conatumumab or AMG 479 study and are eligible according to the parent study to receive their next dose of conatumumab (with or without co-therapy), or AMG 479 alone. Subjects must have their eligibility assessed for this study and be enrolled within 30 days of their last treatment on the parent protocol Exclusion Criteria: Discontinued from a conatumumab study due to an adverse event considered by the investigator to be related to conatumumab treatment, including intolerance to conatumumab Subjects determined to have disease progression during their participation in the parent Amgen study Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last dose of protocol-specified therapy administration Subject is pregnant or breast feeding, or planning to become pregnant within 6 months after the last dose of protocol-specified therapy administration Male subject with a pregnant partner who is not willing to use a condom during treatment and for an additional 6 months after the last dose of protocol-specified therapy administration Subject has previously entered this study Subject will not be available for protocol required study visits, to the best of the subject and investigator's knowledge Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conatumumab Monotherapy<br>Participants will continue to receive conatumumab every 2 weeks (Q2W) or every 3 weeks (Q3W) at the same dose and regimen as at the conclusion of the parent study. | Biological: Conatumumab<br>* Administered by intravenous infusion Q2W or Q3W.<br>* Other names: AMG 655;|
| Experimental: Conatumumab + Ganitumab<br>Participants will receive conatumumab and ganitumab by intravenous infusion at the same dose and regimen as at the conclusion of the parent study. | Biological: Conatumumab<br>* Administered by intravenous infusion Q2W or Q3W.<br>* Other names: AMG 655;Biological: Ganitumab<br>* Administered by intravenous infusion Q3W or Q4W.<br>* Other names: AMG 479;|
| Experimental: Ganitumab Monotherapy<br>Participants will continue to receive ganitumab Q3W or every 4 weeks (Q4W) at the same dose and regimen as at the conclusion of the parent study. | Biological: Ganitumab<br>* Administered by intravenous infusion Q3W or Q4W.<br>* Other names: AMG 479;|
| Experimental: Conatumumab + mFOLFOX6 ± Bevacizumab<br>Participants will continue to receive conatumumab by intravenous infusion in addition to modified FOLFOX6 chemotherapy with or without bevacizumab. | Drug: Modified FOLFOX6<br>* The mFOLFOX6 regimen is a combination therapy of oxaliplatin 85 mg/m² administered as a 2-hour intravenous (IV) infusion on day 1 and leucovorin 400 mg/m² racemate or 200 mg/m² levo-leucovorin administered as a 2-hour infusion on day 1, followed by a loading dose of 5-fluorouracil (5-FU) 400 mg/m² IV bolus administered on day 1, then 5-FU 2400 mg/m² via ambulatory pump administered for a period of 46 to 48 hours every 14 days.<br>* Other names: Oxaliplatin-Leucovorin-Fluorouracil chemotherapy;Biological: Conatumumab<br>* Administered by intravenous infusion Q2W or Q3W.<br>* Other names: AMG 655;Biological: Bevacizumab<br>* Administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle.<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment. | From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab. | 
| Number of Participants With Serious Adverse Events | A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: fatal, life threatening (places the participant at immediate risk of death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect, and/or other medically important serious event. | From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Change From Baseline in Blood Pressure | Maximum change from baseline is defined for each participant as the maximum change from baseline value observed across all visits. | Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab. | 
| Minimum Change From Baseline in Blood Pressure | Minimum change from baseline is defined for each participant as the minimum change from baseline value observed across all visits. | Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab. | 
| Number of Participants With CTCAE Grade 3 or Higher Clinical Laboratory Toxicities | Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. | From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab. | 
| Best Overall Response | Radiological assessments to evaluate disease extent (with change compared to nadir from the parent protocol) were performed at regular intervals, at a minimum once every 6 months or more frequently if clinically indicated (starting from their last scan on the parent protocol), per standard of care (SOC) at each facility. Tumor response was assessed by the Investigator as either complete response, partial response, stable disease, or progressive disease. | Approximately every 6 months until end of treatment; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab. | 
| Number of Participants With Disease Progression or Death Due to Disease Progression |  | From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab. | 

 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, Bevacizumab, Modified FOLFOX6, mFOLFOX6, FOLFOX, Lymphoma, Trail Receptor, ganitumab, conatumumab