Claudin18.2 CAR-T (CT041) in Patients with Gastric, Pancreatic Cancer, or Other Specified Digestive Cancers

NCT04404595 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CT041-ST-02
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 16

Brief Summary

A Phase 1b/2, open label, multi-center, clinical study of Chimeric Antigen Receptor T Cells (CAR-T) targeting claudin18.2 in patients with advanced gastric, pancreatic or other specified digestive system cancers

Conditions

Gastric Cancer; Pancreatic Cancer

Keywords

CAR-T

Outcome Measures

Primary Outcomes (5)

• Phase 1b (Cohort A): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with specified advanced digestive system cancers (STAD, PAAD, or BTC).

  Incidence of adverse events (AEs), AEs of special interest (cytokine release syndrome \[CRS\], neurotoxicity, secondary malignancy), serious adverse events (SAEs).

  up to year 15

• Phase 1b (Cohort A): Identify the recommended Phase 2 dose (RP2D) of CT041 therapy in subjects with advanced STAD, PAAD, or BTC.

  Incidence of dose-limiting toxicities (DLTs)

  day 0 - day 28

• Phase 1b (Cohort A): Identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) of CT041 therapy in subjects with STAD, PAAD, or BTC.

  The highest dose below the dose where the escalation was stopped when the frequency or severity of DLTs exceeds predefined safety criteria.

  day 0 - day 28

• Phase 1b (Cohort B): Determine the efficacy of CT041 by ORR in subjects with advanced STAD, PAAD, or BTC.

  Objective response rate by IRC assessment (RECIST v1.1)

  up to year 15

• Phase 2 (Cohort C): Determine the efficacy of CT041 by ORR in subjects with advanced STAD treated at the RP2D.

  Objective response rate by IRC assessment (RECIST v1.1)

  up to year 15

Secondary Outcomes (20)

• Phase 1b/2: Objective Response Rate (ORR) per investigator assessment

  up to year 15

• Phase 1b (Cohort A): Duration of Response

  up to year 15

• Phase 1b (Cohort A): Time to Progression

  up to year 15

• Phase 1b (Cohort A): Disease Control Rate

  up to year 15

• Phase 1b (Cohort A): Progression free survival

  up to year 15

Study Arms (1)

anti-claudin18.2 chimeric antigen receptor T-cell therapy

EXPERIMENTAL

Phase 1b will include two parts, dose escalation phase (Cohort A) followed by a dose expansion phase (Cohort B). Phase 2 (Cohort C) will evaluate the chosen dose in patients with advanced gastric cancer.

Biological: CT041

Interventions

CT041 BIOLOGICAL

treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion

anti-claudin18.2 chimeric antigen receptor T-cell therapy

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily signed the ICF;
• Age ≥ 18 and \< 76 years with pathologically/histologically confirmed diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, referred to collectively as STAD, or pancreatic adenocarcinoma (PAAD);or biliary tract cancers (BTCs, including intrahepatic/extrahepatic cholangiocarcinoma and gallbladder cancer but not ampullary carcinoma);
• Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay;
• Estimated life expectancy \> 4 months\*;
• Failed or been intolerant of prior lines of systemic therapy:
• For screening:
• Leukapheresis can be performed for subjects with STAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
• Leukapheresis can be performed for subjects with PAAD who are receiving first-line treatment, or,
• Leukapheresis can be performed for subjects with BTC who are receiving first-line treatment.
• Baseline\*:
• Subjects with STAD who have progressed or were intolerant of at least 2 prior lines of systemic therapy, or,
• Subjects with PAAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
• Subjects with BTC who have progressed or were intolerant of at least 1 prior line of systemic therapy. For subjects with CCA with who has FGFR2 fusions or rearrangements, or IDH1-mutant must have received FDA-approved target therapies.
• At least 1 measurable lesion per RECIST 1.1\*;
• ECOG performance status of 0 or 1\*;

You may not qualify if:

• Pregnant or lactating women\*;
• HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV), or active syphilis infection;
• Any active infection requiring systemic treatment\*;
• AEs from previous treatment that have not recovered\*;
• Patients who have clinically significant thyroid dysfunction;
• Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell;
• Patients who have received:
• prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) within one year.
• organ transplantation.
• previous anti-claudin18.2 CAR T-cell therapy, mRNA-based cancer immunotherapy, or bispecific T cell engager.
• Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
• Patients with heavy tumor burdens;
• Unstable/active ulcer, anastomotic recurrence with full-thickness tumor infiltration or tumor involving any major vessels, digestive tract bleeding, or recent digestive surgery that may have increased risk of bleeding\*;
• Patients who have a history of esophageal or gastric resection plus current evidence of locally recurrent tumor that involves any major blood vessels or that has evidence of recent bleeding or perforation\*;
• Patients requiring anticoagulant therapy such as warfarin or heparin;

Sponsors & Collaborators

• CARsgen Therapeutics Co., Ltd.: lead

Study Sites (16)

City of Hope

Duarte, California, 91010, United States

Location

University of Southern California

Los Angeles, California, 90089, United States

Location

UCSD

San Diego, California, 92093, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mayo Cancer Hospital

Rochester, Minnesota, 55905, United States

Location

Northwell Cancer Institute

New Hyde Park, New York, 11042, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

TX Oncology-Baylor Charles Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5GH 2C1, Canada

Location

Related Publications (1)

• Botta GP, Chao J, Ma H, Hahn M, Sierra G, Jia J, Hendrix AY, Nolte Fong JV, Ween A, Vu P, Miller A, Choi M, Heyman B, Daniels GA, Kaufman D, Jamieson C, Li Z, Cohen E. Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells. J Immunother Cancer. 2024 Feb 5;12(2):e007927. doi: 10.1136/jitc-2023-007927.

  PMID: 38316518 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Harry H Yoon, MD

  Mayo

  PRINCIPAL INVESTIGATOR

• Dae Won Kim, MD

  Moffitt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation and expansion

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: May 27, 2020
• Study Start: October 23, 2020
• Primary Completion: June 1, 2025
• Study Completion (Estimated): September 1, 2035
• Last Updated: January 8, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); CA (1)