CT041: treatment with anti-claudin18.2 chimeric antigen receptor T-cell infusion
Study 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
Eligibility
Sex
ALL
Min age
18 Years
Max age
76 Years
Healthy volunteers
No
Inclusion Criteria:
Patients are eligible for screening for potential inclusion in the study (\* indicates inclusion criteria at Baseline (for subjects to be eligible for preconditioning)):
1. Voluntarily signed the ICF;
2. 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);
3. Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay;
4. Estimated life expectancy \> 4 months\*;
5. Failed or been intolerant of prior lines of systemic therapy:
1. 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.
2. 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.
6. At least 1 measurable lesion per RECIST 1.1\*;
7. ECOG performance status of 0 or 1\*;
8. Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
9. Patients should have adequate CBC counts, renal and hepatic functions\*;
10. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception\*;
11. Men must be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion\*;
12. Sufficient nutritional status.
Exclusion Criteria for screening (\* indicates exclusion criteria for baseline as well):
1. Pregnant or lactating women\*;
2. HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV), or active syphilis infection;
3. Any active infection requiring systemic treatment\*;
4. AEs from previous treatment that have not recovered\*;
5. Patients who have clinically significant thyroid dysfunction;
6. Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell;
7. Patients who have received:
1. prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) within one year.
2. organ transplantation.
3. previous anti-claudin18.2 CAR T-cell therapy, mRNA-based cancer immunotherapy, or bispecific T cell engager.
8. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
9. Patients with heavy tumor burdens;
10. 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\*;
11. 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\*;
12. Patients requiring anticoagulant therapy such as warfarin or heparin;
13. Patients requiring long-term antiplatelet therapy;
14. Use of prednisone \>/= 10mg daily or other equivalent steroids within 14 days before leukapheresis or preconditioning\*;
15. Anticancer treatment within approximately 2 weeks prior to leukapheresis or preconditioning\*;
16. Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning\*;
17. Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients\*;
18. Inadequate pulmonary function\*;
19. Patients known to have active autoimmune diseases;
20. Patients with second malignancies;
21. Patients have significant neurologic disorders;
22. Patients are unable or unwilling to comply with the requirements of clinical trial.
Additional exclusion criteria solely for baseline (prior to conditioning regimen):
23. Fever \> 38.0°C;
24. Active illness or existing toxicity that would place the subject at undue risk;
25. Abrupt deterioration of clinical status or condition;
26. Subjects who have received a live attenuated vaccine 4 weeks before preconditioning.
Inclusion Criteria Before Infusion: There are no inclusion criteria at this timepoint.
Exclusion Criteria Before Infusion:
1. Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
2. Inadequate pulmonary function;
3. Active infection requiring systemic therapy or causing fever within 7 days prior to investigational infusion;
4. Active illness or toxicity that would place the subject at undue risk;
5. Abrupt deterioration of clinical status or condition;
6. New or worsening Grade ≥ 3 non-hematologic toxicities.
Primary outcome measure(s)
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). — up to year 15 Incidence of adverse events (AEs), AEs of special interest (cytokine release syndrome \[CRS\], neurotoxicity, secondary malignancy), serious adverse events (SAEs).
Phase 1b (Cohort A): Identify the recommended Phase 2 dose (RP2D) of CT041 therapy in subjects with advanced STAD, PAAD, or BTC. — day 0 - day 28 Incidence of dose-limiting toxicities (DLTs)
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. — day 0 - day 28 The highest dose below the dose where the escalation was stopped when the frequency or severity of DLTs exceeds predefined safety criteria.
Phase 1b (Cohort B): Determine the efficacy of CT041 by ORR in subjects with advanced STAD, PAAD, or BTC. — up to year 15 Objective response rate by IRC assessment (RECIST v1.1)
Phase 2 (Cohort C): Determine the efficacy of CT041 by ORR in subjects with advanced STAD treated at the RP2D. — up to year 15 Objective response rate by IRC assessment (RECIST v1.1)
Trial sites (16)
Facility
City
Region
Status
City of Hope
Duarte
California
University of Southern California
Los Angeles
California
UCSD
San Diego
California
UCSF
San Francisco
California
Moffitt Cancer Center
Tampa
Florida
University of Kansas Cancer Center
Kansas City
Kansas
Karmanos Cancer Center
Detroit
Michigan
Mayo Cancer Hospital
Rochester
Minnesota
Northwell Cancer Institute
New Hyde Park
New York
The Mount Sinai Hospital
New York
New York
Memorial Sloan Kettering Cancer Center
New York
New York
Ohio State University
Columbus
Ohio
TX Oncology-Baylor Charles Sammons Cancer Center
Dallas
Texas
MD Anderson Cancer Center
Houston
Texas
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee
Wisconsin
Princess Margaret Hospital
Toronto
Ontario
More CARsgen Therapeutics Co., Ltd. trials in the USA
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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