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

Phase 2TerminatedNCT00819169

NantCell, Inc.89 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Colorectal Cancer Locally Advanced Metastatic Cancer Non-Small Cell Lung Cancer Ovarian Cancer

Interventions

AMG 479BIOLOGICAL

AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.

AMG 655BIOLOGICAL

AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5.

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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 frame: 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 frame: Time from first dose up to 24 months

Secondary Outcomes

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 frame: Time from first dose up to 24 months

To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation

Time frame: 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.

Time frame: 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.

Time frame: 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 frame: 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 frame: Time from objective response to 24 months