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

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

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).

Study Overview

• Status: Terminated
• Conditions: Advanced Gastrointestinal Tumors
• Intervention / Treatment: Biological: LCAR-G08 cells

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 102200
      • Beijing GoBroad Hospital
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital & Institute

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chimeric Antigen Receptor T cell LCAR-G08 Cells; Each subject will receive LCAR-G08 Cells	Biological: LCAR-G08 cells; Prior to infusion of the LCAR-G08, subjects will receive a conditioning premedication regimen consisting of cyclophosphamide and fludarabine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: Nanjing Legend Biotech Co.
• Investigators: Principal Investigator: Lin Shen, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2023
• Primary Completion (Actual): October 22, 2025
• Study Completion (Actual): October 22, 2025

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: January 7, 2024
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Gastrointestinal Tumors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: LB2301-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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