Clinical trial NCT06197178: A Study of LCAR-G08 in Subjects With Advanced Gastrointestinal Tumors Expressing Guanylyl Cyclase C (GCC)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Gastrointestinal Tumors
Keywords: Advanced Gastrointestinal Tumors
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2024-01-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT) rate
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Recommended Phase 2 Dose (RP2D) regimen finding
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Maximum concentration (Cmax)
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Time to Cmax (Tmax)
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Time to the last observed concentration
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Area Under the Curve (AUC) last
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
Secondary outcomes:
measure: Objective Response Rate (ORR) after administration
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Disease Control Rate (DCR) after administration
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Duration of Remission (DoR) after administration
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Time to Response (TTR) after administration
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Progression-free Survival (PFS) after administration
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Overall Survival (OS) after administration
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
measure: Incidence of anti-LCAR-G08 antibody and positive sample titer
timeFrame: Minimum 2 years after LCAR-G08 infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital & Institute
state: Beijing
city: Beijing
country: China
facility: Beijing GoBroad Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen
role: PRINCIPAL_INVESTIGATOR
References: