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

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

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.

Study Overview

• Status: Terminated
• Conditions: Sarcoma; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer; Non-Small Cell Lung Cancer; Metastatic Cancer; Solid Tumors; Locally Advanced
• Intervention / Treatment: Biological: AMG 479; Biological: AMG 655

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicities	Incidence of adverse events and clinical laboratory abnormalities defined as DLTs. Dose-limiting toxicities included any grade 3 or higher hematologic or nonhematologic toxicity related to conatumumab or the combination of conatumumab with ganitumab except for lymphocytopenia and anemia.	Time from first dose up to 24 months
Objective Response Rate	The objective response rate (ORR) is defined as confirmed complete response or partial response using modified Response Evaluation Criteria in Solid Tumors [RECIST]: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Time from first dose up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression-free survival is defined as the number of days from study day 1 (first dose of investigational product) to the first observation of disease progression (by modified RECIST; or clinical progression, whichever came first) or death due to any cause. Disease progression by RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.	Time from first dose up to 24 months
To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation		Time from first dose up to 24 months
To Evaluate the Concentration Level of AMG 655	Median, minimum, and maximum concentration of AMG 655 at specified time points.	Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
To Evaluate the Concentration Level of AMG 479	Median, minimum, and maximum concentration of AMG 479 at specified time points.	Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
Time to Response	Time to response is the time from study day 1 to the first observation of an objective response. Subjects without an objective response are excluded from the analysis of this endpoint. Objective response is defined as a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors (RECIST) and will be determined based on the Investigator-reported assessment only for subjects with measurable disease at baseline. Per RECIST v 1.1: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Time from first dose up to 24 months
Duration of Response	Duration of response is defined as the number of days between the date of first objective response to the time of the first progressive disease (per modified Response Evaluation Criteria in Solid Tumors [RECIST] or clinical progression, whichever occurs first) or death due to any cause. Objective response is defined as a tumor response assessment of either complete response or partial response per modified RECIST where a complete response is the disappearance of all target lesions and a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Per RECIST v 1.1, disease progression is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.	Time from objective response to 24 months

Collaborators and Investigators

• Sponsor: NantCell, Inc.
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Chawla S, Tabernero, J, Kindler, H., Reckamp, K., Chiorean, E., Azad, N., Lockhard, A., Hsu, CP., Baker, N., Galimi, F., Beltran, P., Baselga, J..Anticancer activity of the type I insulin-like growth factor receptor antagonist, ganitumab, in combination with the death receptor 5 agonist, conatumumab.Targeted Oncology;Tabernero J, Chawla SP, Kindler H, Reckamp K, Chiorean EG, Azad NS, Lockhart AC, Hsu CP, Baker NF, Galimi F, Beltran P, Baselga J. Anticancer activity of the type I insulin-like growth factor receptor antagonist, ganitumab, in combination with the death receptor 5 agonist, conatumumab. Target Oncol. 2014 May 11. [Epub ahead of print]
• Tabernero J, Chawla SP, Kindler H, Reckamp K, Chiorean EG, Azad NS, Lockhart AC, Hsu CP, Baker NF, Galimi F, Beltran P, Baselga J. Anticancer activity of the type I insulin-like growth factor receptor antagonist, ganitumab, in combination with the death receptor 5 agonist, conatumumab. Target Oncol. 2015 Mar;10(1):65-76. doi: 10.1007/s11523-014-0315-z. Epub 2014 May 11.

Helpful Links

• AmgenTrials clinical trials website
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2009
• Primary Completion (Actual): August 10, 2011
• Study Completion (Actual): August 10, 2011

Study Registration Dates

• First Submitted: January 6, 2009
• First Submitted That Met QC Criteria: January 6, 2009
• First Posted (Estimated): January 8, 2009

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Monoclonal Antibody; AMG 479; Tumor Necrosis Factor; Apoptosis; AMG 655; Insulin-like Growth Factor
• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Conatumumab
• Other Study ID Numbers: 20070411; QUILT-3.026 (Other Identifier: NantCell, Inc.)