Phase II Study of Neoadjuvant Immune Checkpoint Inhibitor in Patients With Resectable Gastrointestinal Cancers

NCT04196465 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2019-0988
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Subjects With Resectable and Localized Gastric Cancer; Subjects With Resectable Esophageal Cancer or Liver Cancer; Subjects With Resectable Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Major pathologic response rate

  Evaluation of major pathologic response rate (a proportion of residual viable tumor cells \<10%) after administration of pre-operative immune checkpoint inhibitor IMC-001

  After surgical resection within 28days

Secondary Outcomes (9)

• The safety and feasibility

  Within 14 days after the end of Cycle 2 (+,- 4days)

• R0 resection rate

  After surgical resection within 1 month

• Clinical tumor response rate

  1 month

• Clnical disease control rate

  1 month

• Progression-free survival

  2 years

Other Outcomes (1)

• Discovery of predictive and/or prognostic biomarkers

  2 years

Study Arms (1)

Neoadjuvant IMC-001

EXPERIMENTAL

Neoadjuvant immune check point inhibitor of IMC-001 in participants with resectable and localized gastric cancer, esophageal cancer, and hepatocellular carcinoma

Drug: IMC-001

Interventions

IMC-001 DRUG

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

Neoadjuvant IMC-001

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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.
• Measurable or evaluable lesion(s) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Refer to Supplement 3).
• 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).

You may not qualify if:

• Curatively unresectable or metastatic disease
• Patients with history of other cancers within three years prior to the study treatment. However, patients with other cancers with less influence on their prognosis such as carcinoma in situ or thyroid papillary carcinoma, in the opinion of the investigator, can be enrolled into the study.
• History of hepatic encephalopathy.
• Clinically significant ascites defined as follows:
• A. When screening, the physical examination reveals ascites or
• B. Previous ascites that required treatment and continuous prevention or current ascites that require treatment.
• History of active autoimmune disease with systematic treatment (i.e. immunomodulator, corticosteroid, or immunosuppressant) required within the past 2 years. Replacement therapy (e.g. physiological corticosteroid replacement therapy due to dysfunction of thyroxine, insulin, adrenal gland, or pituitary gland, etc.) is not regarded as a form of systematic treatment and would be allowed.
• Diagnosis of immunodeficiency or within 7 days prior to the first administration of investigational medicinal product treatments with chronic systematic steroids (the dose equivalent to 10 mg/day of prednisone) or immunosuppressive therapy in any other forms are not permitted.
• History of non-infectious interstitial pneumonia requiring treatment of steroids or currently diagnosed.
• Any prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or other antibodies or drugs, specifically target co-stimulatory T cells or immune checkpoint pathways.
• Any known hypersensitivity or anaphylaxis of severeness to recombinant proteins containing monoclonal antibodies.
• Active infection with systematic treatment required.
• From the viewpoint of the investigator, medical conditions, treatments, or laboratory test abnormalities that are likely to cause confusion in clinical trial results, or that are likely to interfere with subjects' participation throughout the entire study, or that are not considered to be in the best interests of the subjects.
• Positive urine test or blood pregnancy test in childbearing females within 7 days prior to the first administration of investigational medicinal product.
• Pregnant or lactating, or during the scheduled study period of 90 days after the final administration of investigational medicinal product, subjects have a plan to have conception.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

IMC-001

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor

Model Details: This study is a prospective, IMC-001 single arm, open label, single center, phase II study.

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: December 12, 2019
• Study Start: September 9, 2019
• Primary Completion (Estimated): September 9, 2026
• Study Completion (Estimated): September 26, 2026
• Last Updated: April 10, 2025

Record last verified: 2025-04

Locations

KR (1)