A Study of LCAR-G08 in Subjects With Advanced Gastrointestinal Tumors Expressing Guanylyl Cyclase C (GCC)

Advanced Gastrointestinal Tumors Clinical Trial

Official title:

A Phase 1, Open-Label Study Evaluating the Safety, Tolerability and Efficacy of (LCAR)-G08, a Chimeric Antigen Receptor (CAR)-T Cell Therapy Targeting Guanylyl Cyclase C (GCC) in Subjects With Advanced Gastrointestinal Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06197178
• Other study ID #: LB2301-0001
• Status: Recruiting
• Phase: Phase 1
• Start date: January 2024
• Est. completion date: March 2028

Study information

• Verified date: December 2023
• Source: Peking University
• Contact: Lin Shen
• Phone: 010-88196561
• Email: Doctorshenlin[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1, single-arm, open-label, dose escalation and expansion study of LCAR-G08 in adult subjects with advanced gastrointestinal tumors expressing guanylyl cyclase C (GCC).

Description:

This is a phase 1, single-arm, open-label, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the cell-based LCAR- G08 in subjects with guanylyl cyclase C (GCC)-positive advanced gastrointestinal tumors. Subjects who meet the eligibility criteria will receive LCAR-G08 infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: March 2028
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Voluntary agreement to provide written informed consent.
• Histologically confirmed metastatic colorectal cancers and other advanced gastrointestinal cancers (esophageal cancer, gastric cancer, pancreatic cancer, and small bowel cancer).
• Aged 18 to 70 years, either sex.
• GCC immunohistochemistry (IHC) staining is positive.
• At least one measurable tumor lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Expected survival = 3 months.
• Clinical laboratory values meet screening visit criteria.

Exclusion Criteria:

• Previous CAR-T cell, T cell receptor-engineered (TCR) T cell, or therapeutic tumor vaccination treatment within the past 6 months; and the corresponding CAR-T, TCR-T cells can still be detected.
• Ever received any treatment targeting GCC.
• Prior antitumor therapy with insufficient washout period.
• Brain metastases.
• Pregnant or lactating women.
• Hepatitis C virus (HCV) antibody-positive or human immunodeficiency virus (HIV) antibody-positive, active syphilis, Epstein-Barr virus (EBV) infected.
• Severe underlying disease.
• Presence of other serious pre-existing medical conditions that may limit patient participation in the study.Any condition that, in the investigator's judgment, will make the subject unsuitable for participation in this study. Any condition that, in the investigator's judgment, will make the subject unsuitable for participation in this study.

Related Conditions & MeSH terms

• Advanced Gastrointestinal Tumors
• Digestive System Neoplasms
• Gastrointestinal Neoplasms

Intervention

Biological:
• LCAR-G08 cells
Prior to infusion of the LCAR-G08, subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital & Institute	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University	Nanjing Legend Biotech Co.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT) rate	Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Primary	Incidence, severity, and type of treatment-emergent adverse events (TEAEs)	An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Primary	Recommended Phase 2 Dose (RP2D) regimen finding	RP2D established through accelerated titration design (ATD) and Bayesian Optimal Interval (BOIN) design.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Primary	Maximum concentration (Cmax)	The maximum observed concentration of CAR positive T cells or transgene CAR copy number after LCAR-G08 infusion.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Primary	Time to Cmax (Tmax)	The time it takes to reach the maximum concentration or time to Cmax after LCAR-G08 infusion.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Primary	Time to the last observed concentration	The time it takes to reach the last observed concentration after LCAR-G08 infusion.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Primary	Area Under the Curve (AUC) last	The total exposure of the drug experienced by the subject in a clinical study from LCAR-G08 infusion to time to the last observed concentration.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary	Objective Response Rate (ORR) after administration	Objective Response Rate (ORR) is defined as the proportion of subjects who achieve complete response (CR) or partial response (PR) after treatment via LCAR-G08 cell infusion, and the objective tumor response rate will be calculated for patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 only.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary	Disease Control Rate (DCR) after administration	Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary	Duration of Remission (DoR) after administration	Duration of Remission (DoR) is defined as the time from the first documentation of remission (PR or better) to the first documented disease progression evidence (according to RECIST 1.1) of the responders (who achieve PR or better response).se).	Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary	Time to Response (TTR) after administration	Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-G08 to the date of the first response evaluation of the subject who has met all criteria for PR or better.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary	Progression-free Survival (PFS) after administration	Progression-free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-G08 to the first documented disease progression (according to RECIST 1.1) or death (due to any cause), whichever occurs first.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary	Overall Survival (OS) after administration	Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-G08 to death of the subject.	Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary	Incidence of anti-LCAR-G08 antibody and positive sample titer	Venous blood samples will be collected to measure LCAR-G08 positive cell concentrations and the transgenic level of LCAR-G08, at the time points when anti-LCAR-G08 antibody serum samples are evaluated.	Minimum 2 years after LCAR-G08 infusion (Day 1)