Subjects With Resectable and Localized Gastric Cancer, Subjects With Resectable Esophageal Cancer or Liver Cancer, Subjects With Resectable Liver Cancer
Conditions
Brief summary
This is a phase II, open-label, prospective single-centered study. Subjects who meet the inclusion/exclusion criteria will be allocated to appropriate cohorts: 1) gastric cancer, 2) esophageal cancer and 3) hepatocellular carcinoma. Each cancer cohort group will be treated with two cycles of neoadjuvant immune checkpoint inhibitor of IMC-001 (1 cycle = 2 weeks) followed by curative resection and be followed up consecutively.
Detailed description
This is a phase II, open-label, prospective single-centered study. Subjects who meet the inclusion/exclusion criteria will be allocated to appropriate cohorts: 1) gastric cancer, 2) esophageal cancer and 3) hepatocellular carcinoma. Each cancer cohort group will be treated with two cycles of neoadjuvant immune checkpoint inhibitor of IMC-001 (1 cycle = 2 weeks) followed by curative resection and be followed up consecutively. The sample size of the study is determined based on a major pathologic response rate (primary endpoint) and by using Simon's single stage design from the subjects who receive preoperative neoadjuvant therapy of IMC-001. In each cancer cohort group, the null and alternative response rates are assumed as 5% and 20%, respectively. This provides a power of 80% when calculating the difference between major pathologic response rates of 5% and 20% in two-tailed significance level of 0.153 (Type I error\[two-tailed\] of 15.3%). In order to reject the null hypothesis, at least two major pathological respondents are needed among 14 assessable subjects for each cancer cohort. After choosing the margin of safety as 10%, each cancer cohort will require 16 subjects and therefore a total of 48 subjects will be enrolled into the study.
Interventions
DRUGIMC-001
IMC-001 is a fully human anti-programmed cell death ligand 1 (PD-L1) recombinant monoclonal antibody that strongly binds to PD-L1 to inhibit its binding to programmed cell death protein 1 (PD-1) or B7-1 (CD80). IMC-001 showed robust dose-dependent efficacy in animal models and no evidence of toxicity in cynomolgus monkeys
Sponsors
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is a prospective, IMC-001 single arm, open label, single center, phase II study.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\<Disease-related inclusion criteria\> 1. Histologically confirmed localized gastric adenocarcinoma, esophageal squamous cell carcinoma, hepatocellular carcinoma or clinically diagnosed hepatocellular carcinoma according to American Association for the Study of Liver Disease (AASLD) guidelines.However, in cases of hepatic carcinoma that can be clinically diagnosed according to AASLD guideline, no biopsy is performed. 2. Curatively resectable gastric adenocarcinoma, esophageal squamous cell carcinoma or hepatocellular carcinoma A. Gastric adenocarcinoma: clinical stage ≥T2 or regional lymph node metastasis (N+) (AJCC 8th) B. Esophageal squamous cell carcinoma: clinical stage ≥T1b or N+ (AJCC 8th) C. Hepatocellular carcinoma: a single hepatocellular carcinoma limited to liver or 3 or less hepatocellular carcinoma limited to liver without invasion to main portal trunk 3. The requirements for hematology, blood chemistry, and functionality in major organs are as follows (should be met within 7 days prior to the first administration of investigational medicinal product): A. Absolute neutrophil count ≥1,000/μL B. Platelets count ≥75,000/μL C. Total bilirubin ≤1.5 × Upper limit of Normal (ULN) (subjects with Gilbert syndrome: bilirubin ≤ 3.0 × ULN) D. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN E. Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/minute (creatinine clearance is first calculated by the formula of Cockcroft-Gault and in case of the value less than 50 mL/min, by collecting and examining 24-hour urine the subjects with the creatine clearance ≥50 mL/minute can be enrolled) (Refer to Supplement 1). F. Urine protein-creatinine ratio (UPC) ≤1 (in case of UPC \>1, by collecting and examining 24-hour urine the subjects with the urine protein \<2 g/day can be enrolled) G. Also, in case of hepatocellular carcinoma, liver function with Child-Pugh grade A (Refer to Supplement 2) and encephalopathy grade 0. 4. Measurable or evaluable lesion(s) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Refer to Supplement 3). 5. Tumor tissue specimen, classified as appropriate for biomarker analysis, must be provided (in case of hepatocellular carcinoma, subjects, without tissue specimen prior to the administration of investigational medicinal product, are allowed for enrollment into the study). \<General inclusion criteria\> 6. Aged ≥ 19 years old 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 8. Signed informed consent form 9. In the case of fertility men and women, Those who should be using adequate contraceptive measures while on study drug and for 3months following the last dose of study drug.
Exclusion criteria
\<Tumor-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major pathologic response rate | After surgical resection within 28days | Evaluation of major pathologic response rate (a proportion of residual viable tumor cells \<10%) after administration of pre-operative immune checkpoint inhibitor IMC-001 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The safety and feasibility | Within 14 days after the end of Cycle 2 (+,- 4days) | Evaluation of safety assessed by NCI CTCAE v. 4.03 and evaluation of feasibility assessed by the occurrence of delays in prearranged surgery. |
| R0 resection rate | After surgical resection within 1 month | Evaluation of R0 resection rate |
| Clinical tumor response rate | 1 month | Evaluation of clinical tumor response rate by RECIST v1.1 |
| Clnical disease control rate | 1 month | Evaluation of clinical disease control rate by RECIST v1.1 |
| Progression-free survival | 2 years | Evaluation of progression-free survival |
| Relapse-free survival | 2 years | Evaluation of relapse-free survival |
| Overall survival | 2 years | Evaluation of overall survival |
| The rates and patterns of cancer progression/relapse | 2 years | Evaluation of the rates of cancer progression/relapse |
| Patterns of cancer progression/relapse | 2 years | Evaluation of the pattern of cancer progression/relapse |
Countries
South Korea
Outcome results
None listed