A Phase I Dose Escalation Study, With Cohort Expansion, to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AbGn-107 Therapy in Patients With Chemo-refractory Locally Advanced, Recurrent, or Metastatic Gastric, Colorectal, Pancreatic or Biliary Cancer

AbGenomics B.V Taiwan Branch9 sites in 2 countries39 target enrollmentApril 24, 2017

ConditionsGastric Cancer Colorectal Cancer Pancreatic Cancer Biliary Cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Gastric Cancer
Sponsor: AbGenomics B.V Taiwan Branch
Enrollment: 39
Locations: 9
Primary Endpoint: Adverse events (AEs) graded according to CTCAE v4.03.
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This study is to define the safety profile and to determine the Maximal tolerated dose regimen and preliminary efficacy of AbGn-107 administered every 14 days (Q2W regimen) or 28 days (Q4W regimen) in patients with chemo-refractory locally advanced, recurrent or metastatic gastric, colorectal, pancreatic or biliary cancer.

Detailed Description

AbGn-107 is an antibody drug conjugate (ADC) which targets an antigen (AG7 antigen) present in gastric, colorectal, pancreatic cancer or biliary cancer. This study is a standard 3 + 3 dose escalation design with cohort expansion. AbGn-107 will be administered every 14 days (Q2W regimen) or 28 days (Q4W regimen) in patients with chemo-refractory locally advanced, recurrent or metastatic gastric, colorectal, pancreatic adenocarcinoma or biliary cancer. The primary objectives of this study are to define the safety profile and to determine the maximum tolerated dose regimen of AbGn-107, and the secondary objectives are to evaluate the pharmacokinetic (PK) parameters, the immunogenicity, and preliminary efficacy of AbGn-107.

Registry

clinicaltrials.gov

Start Date

April 24, 2017

End Date

February 28, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

AbGenomics B.V Taiwan Branch

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥18 years. A patient may be of either sex and of any race/ethnicity.
•Histologically confirmed, chemo-refractory, locally advanced, recurrent or metastatic gastric (including GE junction), colorectal, or pancreatic adenocarcinoma or biliary cancer (including cholangiocarcinoma, gallbladder and ampullary carcinomas).
•Patient must not have curative options available (e.g. a single metastatic focus in the liver in a patient with MCRC eligible for metastasectomy).
•Chemo-refractory is defined as:
•Progression on or following, or intolerant of, at least one prior line of standard systemic therapy for advanced or metastatic gastric or pancreatic or biliary cancers.
•Progression on or following, or intolerant of, at least two prior lines of standard systemic therapy for advanced or metastatic colorectal cancers.
•Patients who have progressed/recurred following neoadjuvant/adjuvant chemotherapy for earlier stage disease, if completed within the previous 6 months, are eligible.
•Archived tissue must be available for all patients (both dose escalation and expansion cohorts). Dose Escalation Only-If tissue is not available, patients may still be considered eligible for enrollment, if all other eligibility criteria are confirmed and after discussion with and approval by the sponsor medical monitor. Cohort Expansion Only-Tissue must be to confirmed high expression of AG7 antigen during the Pre-Screening period, defined as immune reactive score (IRS) ≥8, via slides from original diagnostic biopsy material or biopsy of recurrent/metastatic disease, prior to enrollment.
•Measurable disease by RECIST 1.1 criteria
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-

Exclusion Criteria

•Any persistent, unresolved Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 drug-related toxicity (except alopecia, erectile impotence, tinnitus, hot flashes, and loss of libido) associated with previous treatment. Inclusion of patients with persistent neuropathy or hearing loss Grade ≥2 due to previous treatment requires discussion with the sponsor.
•Radiation therapy within 2 weeks prior to first study drug administration.
•Major surgery within 3 weeks prior to first study drug administration.
•Any chemotherapy within 30 days of enrollment.
•Participation in any other clinical study with a potentially therapeutic agent or receipt of another investigational product within 21 days or 5 plasma half-lives, whichever is longer, prior to first day of drug administration (Day 1).
•Active central nervous system metastases. Patients with a history of brain metastases may be eligible, provided they have been definitively treated and are clinically stable, after discussion with sponsor. Treated or untreated leptomeningeal disease is not permitted.
•Known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy. Note: HIV testing is not required unless there is any clinical suspicion that the patient might be HIV positive.
•Known active hepatitis B or C. HBV and HCV tests are required prior to Day
•Any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would impair with their ability to receive or tolerate the planned treatment, or interfere with the study evaluations or optimal participation in the study.
•Pregnancy or breastfeeding.

Outcomes

Primary Outcomes

Adverse events (AEs) graded according to CTCAE v4.03.

Time Frame: 28 days

Secondary Outcomes

Overall Response Rate Evaluated by Response Evaluation Criteria in Solid Tumor (RECIST)(Every 2 treatment cycles for Q4W regimen or every 4 treatment cycles for Q2W regimen, up to 2 years from the first patient enrolled)
Tmax (time from dosing to maximum measured concentration)(70 days after treatment)
T1/2 (half-life of the analyte)(70 days after treatment)
Immunogenicity evaluation based on anti-drug antibodies titer(70 days after treatment)
Cmax (maximum measured concentration of the analyte in plasma)(70 days after treatment)