Brief Title
A Study of AbGn-107 in Patients With Gastric, Colorectal, Pancreatic or Biliary Cancer
Official Title
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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Adverse events (AEs) graded according to CTCAE v4.03.
Secondary Outcome
Cmax (maximum measured concentration of the analyte in plasma)
Condition
Gastric Cancer
Intervention
AbGn-107
Study Arms / Comparison Groups
AbGn-107
Description: AbGn-107 will be administered every 14-days or 28-days via intravenous infusion. Patients with a complete response (CR), partial response (PR), or stable disease (SD), or with evidence of clinical benefit may be treated every continuously every 14-days or 28-days..
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
39
Start Date
April 24, 2017
Completion Date
February 28, 2021
Primary Completion Date
February 28, 2021
Eligibility Criteria
Inclusion Criteria:
1. Age ≥18 years. A patient may be of either sex and of any race/ethnicity.
2. 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).
1. Patient must not have curative options available (e.g. a single metastatic focus
in the liver in a patient with MCRC eligible for metastasectomy).
2. 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.
3. 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.
4. Measurable disease by RECIST 1.1 criteria
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
6. Adequate organ function within 3 weeks prior to first study drug administration as
evidenced by:
1. Absolute neutrophil count ≥1.5 x 10^9/L,
2. Hemoglobin ≥9 g/dL,
3. Platelet count ≥100 x 10^9/L,
4. Serum creatinine ≤1.5 x upper limit of normal (ULN) or a calculated creatinine
clearance >60 mL/min,
5. Total bilirubin <1.5 x ULN, except for patients with Gilbert's disease who are
eligible if total bilirubin ≤ 3 mg/dL.
6. Aspartate aminotransferase (AST)/serum glutamic-oxalacetic transaminase (SGOT)
and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT)
<2.5 x ULN, or, in the presence of documented liver metastases, ≤5 x ULN.
7. Ability to adhere to dose and visit schedules.
8. Women of childbearing potential (WOCP) must have a negative pregnancy test result
prior to enrollment. WOCP and men whose partners are WOCP must agree to use a highly
effective method of birth control during the study and for 6 months following the last
dose of study drug. A highly effective method of birth control is defined as one which
results in a low failure rate (less than 1% per year).
9. Ability to provide written informed consent
10. Life expectancy of at least 3 months.
Exclusion Criteria:
1. 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.
2. Radiation therapy within 2 weeks prior to first study drug administration.
3. Major surgery within 3 weeks prior to first study drug administration.
4. Any chemotherapy within 30 days of enrollment.
5. 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).
6. 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.
7. 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.
8. Known active hepatitis B or C. HBV and HCV tests are required prior to Day 1.
9. 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.
10. Pregnancy or breastfeeding.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Shih-Yao (David) Lin, MD, PhD, ,
Location Countries
Taiwan
Location Countries
Taiwan
Administrative Informations
NCT ID
NCT02908451
Organization ID
2016.006.01
Responsible Party
Sponsor
Study Sponsor
AbGenomics B.V Taiwan Branch
Study Sponsor
Shih-Yao (David) Lin, MD, PhD, Study Director, AbGenomics B.V.
Verification Date
July 2020