Clinical Trial to Evaluate the Safety and Efficacy of IM96 CAR-T Cells Therapy in Patients With Advanced Digestive System Neoplasms

This is a open-label, single center to determine the efficacy and safety of IM96 CAR-T cells in Patients With Advanced Digestive System Neoplasms

Study Overview

• Status: Recruiting
• Conditions: Digestive System Neoplasms; Advanced Solid Tumors; Pancreatic Cancer Resectable; Colorectal (Colon or Rectal) Cancer
• Intervention / Treatment: Drug: IM96 CAR-T cells

• Study Type: Interventional
• Enrollment (Anticipated): 19
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 to 75 years, either sex;
• Patients with pathologically diagnosed advanced gastrointestinal cancer:Patients with metastatic colorectal cancer who have failed or cannot tolerate second-line or above standard treatment;Patients with unresectable locally advanced or metastatic pancreatic cancer who have failed or cannot tolerate first-line or above standard treatment; Patients with unresectable locally advanced or metastatic other gastrointestinal cancer (gastric cancer, esophageal cancer, small intestinal cancer, etc.) who have failed or cannot tolerate standard treatment, or have no standard treatment regimen;
• At least one measurable lesion meeting RECIST 1.1 criteria;
• Tumor tissue samples were positive for GUCY2C IHC staining;
• Estimated life expectancy >3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Women of childbearing age who had a negative blood pregnancy test before the start of the trial and agreed to take effective contraceptive measures during the trial period until the last follow-up; male subjects with fertility partners agreed to take effective contraceptive measures during the trial period until the last follow-up;
• Adequate organ function;
• Volunteer to participate in this trial and sign on the informed consent.

Exclusion Criteria:

• Patients have brain metastasis；
• Patients with a history of organ transplantation or awaiting organ transplantation;
• The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; other tolerable events determined by investigator;
• There is a large amount of serous effusion that cannot be controlled by treatment (such as pleural effusion, peritoneal effusion and pericardial effusion);
• History of autoimmune disease (eg Crohn's disease, rheumatoid arthritis, systemic lupus) within the last 2 years;
• Presence of acute or chronic graft-versus-host disease (GVHD);
• Use prohibited drugs or treatments within a specified period of time before cell collection；
• History or presence of CNS disorder, such as epilepsy, epileptic seizures, cerebrovascular disease (ischemia / hemorrhage / cerebral infarction), brain edema, reversible posterior white matter encephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, cerebral organic syndrome or mental disease;
• Chronic or active infections requiring systemic treatment, and a history of symptomatic viral infection that has not been completely cured；
• Live vaccine received within 6 weeks before the start of screening;
• Cardiac dysfunction includes: long QTc syndrome or QTc interval > 480 MS; Complete left bundle branch block, grade II / III atrioventricular block; Serious and uncontrolled arrhythmias requiring drug treatment; A history of chronic congestive heart failure with NYHA ≥ 3, and the cardiac ejection fraction was less than 50% within 6 months before screening; Cardiac valvular disease with CTC AE ≥ 3; Myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, history of severe pericardial disease or other clinically significant heart diseases within 6 months before screening;
• Patients requiring anticoagulant therapy;
• Patients requiring continuous anti-platelet therapy;
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment;
• A history of malignancy other than non melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast), unless it has been disease-free for at least 3 years;
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and bacterial pharyngitis are permitted if the investigator evaluates that it can be controlled by treatment, they can be included in the group;
• Patients with gastrointestinal obstruction;
• Patients at high risk of hemorrhage or perforation;
• Patients were enrolled in another clinical study at the same time, unless it was an observational (non intervention) clinical study;
• In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IM96 CAR-T cells	Drug: IM96 CAR-T cells; treatment with anti-GUCY2C chimeric antigen receptor T-cell infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Related adverse events (AEs)	Incidence of treatment related AE.	Up to 28 days after CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1	Up to 24 weeks after CAR-T cell infusion
Progression-free survival (PFS)	PFS, defined as the time from CAR-T cell infusion to the first occurrence of disease progression or death from any cause (whichever occurs first) , as determined by the investigator according to RECIST v1.1	Up to 24 weeks after CAR-T cell infusion
Overall survival (OS)	OS , defined as the time from CAR-T cell infusion to death from any cause	Up to 24 weeks after CAR-T cell infusion
Persistence of CAR-T cells (cell counts and cell percentage in peripheral blood)	The persistence over time of CAR T cells in the peripheral blood as determined by flow cytometry and qPCR.	Up to 24 weeks after CAR-T cell infusion
Objective response rate (ORR)	ORR, defined as the proportion of participants with a complete response or partial response, as determined by the investigator according to RECIST v1.1	Up to 24 weeks after CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Beijing Immunochina Medical Science & Technology Co., Ltd.
• Investigators: Principal Investigator: Lin Shen, Ph.D, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Digestive System Neoplasms; Pancreatic Cancer Resectable; Colorectal (Colon or Rectal) Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Pancreatic Diseases; Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: YMCART9601

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No