Study of ABT-700 in Subjects With Advanced Solid Tumors

A Multi-Center, Phase 1/1b, Open-Label, Dose Escalation Study of ABT-700, a Monoclonal Antibody in Subjects With Advanced Solid Tumors

This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-700 in subjects with advanced solid tumors that may have MET amplification or c-Met overexpression. ABT-700, previously known as h224G11 in publications, is an anti-c-Met antibody. The early clinical development plan for ABT-700 is based on the activity demonstrated in preclinical models. Up to 124 subjects will be enrolled.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: ABT-700; Drug: ABT-700; Drug: docetaxel; Drug: FOLFIRI; Drug: cetuximab; Drug: erlotinib

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject with advanced solid tumors; Dose-expansion: evidence for MET gene amplification.
• Subject must have disease: a) that is not amenable to surgical resection, or b) that has progressed or recurred despite standard therapy, or c) that has failed to respond to standard therapy, or d) for which no effective therapy exists.
• Subject cannot tolerate or must not be eligible for other approved therapeutic options with known survival advantage.
• Subjects enrolled on the combination therapy phase must satisfy the above inclusion criteria and also the following: Subjects must have inoperable, locally advanced or metastatic cancer and be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib in combination with ABT-700.

Exclusion Criteria:

• Subject has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days, or herbal therapy within 7 days prior to the first dose of ABT-700.
• Subjects with uncontrolled metastases of the central nervous system. Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease after definitive therapy and have not used steroids for at least 1 month prior to first dose of ABT-700.
• Subject has unresolved adverse events > Grade 1 from prior anticancer therapy except for alopecia or anemia.
• Subject has had major surgery within 21 days prior to the first dose of ABT-700.
• Subjects enrolled on the combination therapy phase must not meet the above exclusion criteria and must be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib per most current prescribing information, or at the discretion of the Investigator. Subjects with K-Ras mutation-positive colorectal cancer will be excluded from receiving FOLFIRI/cetuximab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort A; ABT-700 will be administered by intravenous infusion at escalating dose levels in 21-day dosing cycles. Additional subjects will be enrolled in an expansion cohort that will further evaluate ABT-700.	Drug: ABT-700; ABT-700 will be administered by intravenous infusion at escalating dose levels on day 1 in 21-day dosing cycles. Additional subjects will be enrolled in an dose expansion cohort that will further evaluate ABT-700.; Drug: ABT-700; ABT-700 will be administered by intravenous infusion on Day 1 and Day 15 in 28-day dosing cycles.
EXPERIMENTAL: Cohort B; ABT-700 plus docetaxel.	Drug: ABT-700; ABT-700 will be administered by intravenous infusion at escalating dose levels on day 1 in 21-day dosing cycles. Additional subjects will be enrolled in an dose expansion cohort that will further evaluate ABT-700.; Drug: ABT-700; ABT-700 will be administered by intravenous infusion on Day 1 and Day 15 in 28-day dosing cycles.; Drug: docetaxel; Docetaxel will be administered by intravenous infusion on Day 1 in 21-day dosing cycles.
EXPERIMENTAL: Cohort C; ABT-700 plus FOLFIRI/cetuximab	Drug: ABT-700; ABT-700 will be administered by intravenous infusion at escalating dose levels on day 1 in 21-day dosing cycles. Additional subjects will be enrolled in an dose expansion cohort that will further evaluate ABT-700.; Drug: ABT-700; ABT-700 will be administered by intravenous infusion on Day 1 and Day 15 in 28-day dosing cycles.; Drug: FOLFIRI; 5-fluorouracil, Folinic acid and Irinotecan will be administered by intravenous infusion on Day 1 and 15 in 28-day dosing cycles.; Drug: cetuximab; Cetuximab will be administered by intravenous infusion weekly.
EXPERIMENTAL: Cohort D; ABT-700 plus erlotinib	Drug: ABT-700; ABT-700 will be administered by intravenous infusion at escalating dose levels on day 1 in 21-day dosing cycles. Additional subjects will be enrolled in an dose expansion cohort that will further evaluate ABT-700.; Drug: ABT-700; ABT-700 will be administered by intravenous infusion on Day 1 and Day 15 in 28-day dosing cycles.; Drug: erlotinib; Erlotinib will be taken orally daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib	Evaluation of vital signs, clinical lab testing, physical exams and adverse event monitoring	First cycle of treatment through 60 day follow-up visit
To Evaluate the pharmacokinetics of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib	Pharmacokinetic profile of ABT-700 analyzed from blood samples	At each cycle of treatment through 60 days after last dose.
To determine the recommended Phase 2 dose for ABT-700		First cycle of treatment through 60 day follow-up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the preliminary efficacy of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib	Objective response rate (complete and partial response), progression-free survival and duration of response	Screening through 60 day follow-up visit

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Investigators: Study Director: Louie Naumovski, MD, AbbVie

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 6, 2011
• Primary Completion (ACTUAL): April 27, 2017
• Study Completion (ACTUAL): April 27, 2017

Study Registration Dates

• First Submitted: October 14, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (ESTIMATE): November 16, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Neoplasms; MET amplification; c-Met overexpression; h224G11
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Docetaxel; Erlotinib Hydrochloride; Cetuximab
• Other Study ID Numbers: M12-375