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

NCT06197178 | Terminated Phase 1

• 1 other identifier: LB2301-0001
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Advanced Gastrointestinal Tumors

Keywords

Advanced Gastrointestinal Tumors

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (7)

• Objective Response Rate (ORR) after administration

  Minimum 2 years after LCAR-G08 infusion (Day 1)

• Disease Control Rate (DCR) after administration

  Minimum 2 years after LCAR-G08 infusion (Day 1)

• Duration of Remission (DoR) after administration

  Minimum 2 years after LCAR-G08 infusion (Day 1)

• Time to Response (TTR) after administration

  Minimum 2 years after LCAR-G08 infusion (Day 1)

• Progression-free Survival (PFS) after administration

  Minimum 2 years after LCAR-G08 infusion (Day 1)

Study Arms (1)

Chimeric Antigen Receptor T cell LCAR-G08 Cells

EXPERIMENTAL

Each subject will receive LCAR-G08 Cells

Biological: LCAR-G08 cells

Interventions

LCAR-G08 cells BIOLOGICAL

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

Chimeric Antigen Receptor T cell LCAR-G08 Cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University: lead
• Nanjing Legend Biotech Co.: collaborator

Study Sites (2)

Beijing Cancer Hospital & Institute

Beijing, Beijing Municipality, 100142, China

Location

Beijing GoBroad Hospital

Beijing, Beijing Municipality, 102200, China

Location

Study Officials

• Lin Shen

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Masking Description
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Model Description

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: January 9, 2024
• Study Start: December 28, 2023
• Primary Completion: October 22, 2025
• Study Completion: October 22, 2025
• Last Updated: February 6, 2026

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)