Clinical Study of Pabolizumab for Neoadjuvant Immunotherapy of Locally Advanced Microsatellite-unstable Gastric Adenocarcinoma

Our study is aim to evaluate the efficacy and safety of pabolizumab in neoadjuvant immunotherapy of locally advanced microsatellite-unstable gastric adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Gastric Adenocarcinoma
• Intervention / Treatment: Drug: pabolizumab

Detailed Description

Patients with microsatellite-unstable gastric adenocarcinoma cannot benefit from chemotherapy, According to the guideline of the Chinese Society of Clinical Oncology, It is not recommended to receive chemotherapy for patients with microsatellite-unstable gastric cancer, therefore, immunotherapy is the only hope for those patients.

• Study Type: Observational
• Enrollment (Anticipated): 32

Contacts and Locations

• Study Contact: Name: Jialin Li, MD; Phone Number: 8601088196970; Email: ljldoc@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Jiafu Ji, MD; Phone Number: 0086-01-88196391; Email: jiafuj@hotmail.com
      • Principal Investigator: Zhaode Bu, MD
      • Contact: Jialin Li, MD; Phone Number: 0086-01-88196967; Email: ljldoc@163.com
      • Sub-Investigator: Jialin Li, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with locally advanced microsatellite-unstable gastric adenocarcinoma

Description

Inclusion Criteria:

1. ECOG 0-1.
2. Gastroscopy confirmed adenocarcinoma of the gastroesophageal junction or stomach and biopsy pathology confirmed adenocarcinoma of the stomach.
3. Advanced gastric cancer as assessed by ultrasonography and/or gastric CT (cT3-T4b, Nany, M0).
4. Biopsy tissues with IHC indicates deficient mismatch repair(dMMR),that is, the loss of at least one of the four proteins ,MSH1, MSH2, MSH6, PMS2; or gene detection implies MSI-H;
5. Subjects must have at least one measurable lesion in accordance with RECIST v1.1. A lesion previously treated with local therapies such as radiotherapy can be considered a target lesion if there is objective evidence of progression in the lesion.
6. Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.
7. Has life expectancy of greater than 6 months.
8. Adequate organ function.

Exclusion Criteria:

1. Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
2. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
3. as a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
4. Any disease requiring systemic treatment. Local replacement steroids are permitted
5. Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with the exceptions of the following: vitiligo, alopecia, Grave disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of hormone replacement therapy and type I diabetes only requiring steady doses of insulin replacement therapy, or completely relieved childhood asthma that requires no intervention in adulthood, or primary diseases that will not relapse unless triggered by external factors.
6. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
7. Known history of active tuberculosis (TB).
8. Serious infections within 4 weeks prior to the first dose of study drug, including but not limited to complications requiring hospitalization, sepsis or severe pneumonia.
9. An active infection requiring systemic therapy.
10. Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 2000 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.
11. Known history of testing positive for human immunodeficiency virus (HIV).
12. Any conditions that, in the investigator's opinion, may put subjects treated with the study drug at risks, or interfere with the evaluation of study drug or subject safety, or the interpretation of results.
13. Known history of allergy or hypersensitivity to Pabolizumab or any of its components

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental; pabolizumab	Drug: pabolizumab; pabolizumab IV every 3 weeks (q3w)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) Rate	pCR is defined as absence of viable tumor (pT0pT0N0) in examined tissue	Up to approximately 15 Weeks (Time of surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival is defined as the time from randomization to death due to any cause.	Up to approximately 71 months.
Progression free survival (PFS)	The time from registration to the date of disease progression or death resulting from any cause.	3 years.
R0 resection rate	Proportion of patients who achieved R0 resection.	Within 4 weeks following the operation.

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: April 4, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: neoadjuvant; immunotherapy; PD-1; immuno-oncology; pabolizumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: LGH2021374

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No