Efficacy and Safety of LM-302 Combined With Gemcitabine CLDN 18.2 Positive Unresectable Locally Advanced or Metastatic Pancreatic Cancer

NCT07108504 | Not Yet Recruiting Phase 2

• 1 other identifier: ZSPAC-16
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of LM-302 combined with gemcitabine as a second-line treatment for CLDN 18.2-positive unresectable locally advanced or metastatic pancreatic cancer. The main questions it aim to answer:

1. 1.Does LM-302 plus gemcitabine improve the objective response rate (ORR, per RECIST 1.1) compared to historical controls?
2. 2.What is the safety and tolerability profile of this combination therapy?
3. 3.Gemcitabine (1000 mg/m² IV on Days 1, 8, and 15) in 4-week cycles, and LM-302 (1.8 mg/kg IV on Day 1) in 2-week cycles,
4. 4.Undergo regular tumor imaging (CT/MRI) and safety assessments;
5. 5.Provide blood samples for biomarker and pharmacokinetic analyses.

Conditions

Pancreatic Cancer; Chemotherapy Effect

Keywords

pancreatic adenocarcinoma; CLDN18.2; LM302; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) per RECIST 1.1

  The proportion of participants with CLDN18.2-positive unresectable locally advanced or metastatic pancreatic adenocarcinoma achieving a best overall response of complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST 1.1 criteria.

  From baseline until disease progression or study completion (up to 24 months).

Secondary Outcomes (5)

• Duration of Response (DOR) per RECIST 1.1

  From first response until progression/death (up to 24 months).

• Disease Control Rate (DCR) per RECIST 1.1

  From baseline until confirmed SD/response (up to 24 months).

• Progression-Free Survival (PFS) per RECIST 1.1

  From first dose of study treatment until disease progression (per RECIST 1.1) or death from any cause, assessed up to 24 months.

• Overall Survival (OS)

  From first dose of study treatment until death from any cause or the end of follow-up, whichever occurs first, assessed up to 36 months.

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From first dose until 30 days after last dose (up to 24 months).

Study Arms (1)

LM-302 combined with Gemcitabine

EXPERIMENTAL

Drug: Gemcitabine; Drug: LM-302

Interventions

Gemcitabine DRUG

Gemcitabine, 1000 mg/m², d1, 8, 15, q4 week

LM-302 combined with Gemcitabine

LM-302 DRUG

LM-302, 1.8 mg/kg, d1, q2 week

LM-302 combined with Gemcitabine

Eligibility Criteria

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

You may qualify if:

• Capable of providing written informed consent, understanding and complying with study requirements. Willing to participate after full disclosure of the study's purpose, procedures, potential risks, and benefits, and must sign the informed consent form before any study-related procedures.
• Age ≥18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no deterioration within 2 weeks before the first dose.
• Expected survival ≥3 months.
• Histologically or cytologically confirmed unresectable, locally advanced, or metastatic pancreatic ductal adenocarcinoma (PDAC) not amenable to curative treatment.
• Must have experienced disease progression or intolerance to first-line standard therapy containing 5-FU (fluorouracil) (radiologically confirmed).
• At least one measurable lesion per RECIST v1.1.
• Must provide 5-7 unstained slides from archived (within 3 years) or fresh tumor tissue for CLDN18.2 and other biomarker testing. CLDN18.2 positivity defined as: Moderate-to-high staining intensity (2+\~3+) in ≥50% of tumor cells, as assessed by central laboratory IHC (immunohistochemistry).
• Adequate Organ Function (within 7 days before first dose) Bone marrow function: Platelets (PLT) ≥90 × 10⁹/L; Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L; Hemoglobin ≥9 g/dL (no erythropoietin \[EPO\], G-CSF, or GM-CSF support within 14 days, and no transfusions within 7 days prior to treatment) Coagulation: INR ≤1.5; APTT ≤1.5 × ULN Liver function: Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert's syndrome); AST/ALT ≤2.5 × ULN (≤5 × ULN if liver metastases present); Serum albumin (ALB) ≥28 g/L Renal function: Serum creatinine ≤1.5 × ULN; Creatinine clearance (CrCl) ≥50 mL/min (calculated by Cockcroft-Gault formula) Cardiac function: Left ventricular ejection fraction (LVEF) ≥50%; QTcF interval ≤470 ms
• Females of childbearing potential and males with fertile partners must agree to use highly effective contraception from 7 days before the first dose until 6 months after the last dose.
• Able to communicate effectively with investigators and comply with all study requirements.

You may not qualify if:

• Previous treatment with gemcitabine or nab-paclitaxel.
• Received any investigational drug or therapy within 28 days before the first dose of the study drug.
• Recent Anticancer Therapy (within 21 days before the first dose, except for): Palliative radiotherapy (e.g., for bone metastasis pain control) within 14 days. Oral drugs (e.g., fluoropyrimidines, small-molecule targeted agents) within 14 days or 5 half-lives (whichever is longer). Traditional Chinese medicine with anticancer indications within 14 days. Nitrosoureas or mitomycin C within 42 days. Therapeutic radiopharmaceuticals within 56 days.
• Residual Toxicities from Prior Therapy Adverse reactions from prior anticancer therapy have not recovered to CTCAE v5.0 Grade ≤1 (except for non-safety risks, such as alopecia, chronic radiotherapy toxicities ≤Grade 2, or lymphopenia).
• Poorly Controlled Tumor-Related Pain Patients requiring analgesics must be on a stable dose before study entry.
• Active or Untreated CNS Metastases Excludes those with previously treated, stable brain metastases (confirmed by imaging ≥4 weeks before the first dose, no new neurological symptoms, and no progression).
• Proteinuria Urine protein ≥3+, or 2+ with 24-hour urine protein \>1 g.
• Recent Life-Threatening Hemorrhage Any major bleeding event within 3 months before the first dose.
• High-Risk Esophageal/Gastric Varices Requires endoscopic evaluation within 3 months before the first dose if there is a history of variceal bleeding.
• Severe Liver Dysfunction Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B/C cirrhosis.
• Uncontrolled Third-Space Fluid Accumulation Clinically significant ascites/pleural effusion requiring repeated drainage, recent intervention (within 14 days), or causing complications (e.g., bowel obstruction).
• Tumor Invasion of Critical Structures Encasement of major vessels (aorta, SVC, etc.) or risk of fistula formation (e.g., tracheoesophageal, pleuroesophageal).
• History of GI Perforation/Fistula Within 6 months before the first dose.
• Bowel Obstruction/Perforation Risk Complete/incomplete intestinal obstruction or high perforation risk within 3 months before the first dose.
• Hypersensitivity to Antibody-Based Therapies History of ≥Grade 3 infusion reactions to monoclonal/bispecific antibodies, ≥Grade 3 immune-related AEs from prior immunotherapy, or discontinuation due to severe immune toxicity.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Wen-Quan Wang, Dr

CONTACT

+86 21 31587861; wang.wenquan@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pancreatic Surgery, Zhongshan Hospital, Fudan University

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 7, 2025
• Study Start: August 10, 2025
• Primary Completion (Estimated): August 10, 2026
• Study Completion (Estimated): August 10, 2028
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share