The Efficacy and Safety of LM-302 in Combination With Candonilimab and Capecitabine for First-Line Treatment in Patients With Unresectable Advanced, Recurrent, or Metastatic CLDN18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma

NCT06587425 | Recruiting Phase 2

• 1 other identifier: LM-302-IIT-203
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase II Study Evaluating the Efficacy and Safety of LM-302 in Combination with Candonilimab and Capecitabine for First-Line Treatment in Patients with Unresectable Advanced, Recurrent, or Metastatic CLDN18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Keywords

CLDN18.2; ADC drug; cadonilimab; Immune Checkpoint Inhibitor; Targeted therapy; Immunotherapy; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  DLT is defined as a toxicity (adverse event at least possibly related to LM302) occurring during the DLT observation period

  Cycle 1 of each cohort. Duration of one cycle is 28 days

• Progression Free Survival (PFS)

  PFS was defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on Investigator assessment

  From enrollment until 6 months after the last participant discontinues treatment, up to approximately 42 months

Secondary Outcomes (5)

• Overall Survival (OS)

  From enrollment until 6 months after the last participant discontinues treatment, up to approximately 42 months.

• Objective response rate (ORR)

  From start of treatment to date of documented disease progression, up to approximately 42 months

• Duration of response (DoR)

  From start of treatment to date of documented disease progression, up to approximately 42 months

• Disease control rate (DCR)

  From start of treatment to date of documented disease progression, up to approximately 42 months

• . AE and SAE

  : From signing the ICF until 28 days after EOT or accept other anti-cancer therapy,up to 40 days after last study dose

Study Arms (1)

LM-302+Cadonilimab+Capecitabine

EXPERIMENTAL

LM-302: 1.8mg/kg ivgtt d1, q2w; Canonilimab: 6mg/kg ivgtt d1, q2w; Capecitabine: 1000mg/m\^2 po bid d1-10, q2w.

Drug: LM-302+Candonilimab+Capecitabine

Interventions

LM-302+Candonilimab+Capecitabine DRUG

LM-302: 1.8mg/kg ivgtt d1, q2w; Canonilimab: 6mg/kg ivgtt d1, q2w; Capecitabine: 1000mg/m\^2 po bid d1-10, q2w.

Also known as: ADC-Claudin18.2+AK104+Capecitabine

LM-302+Cadonilimab+Capecitabine

Eligibility Criteria

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

You may qualify if:

• The subjects fully understand the purpose, nature, methods, and potential adverse reactions of the trial, voluntarily participate as participants, and sign an informed consent form (ICF) before any procedures begin
• The subject must have locally advanced or metastatic gastric cancer or gastroesophageal junction cancer that cannot be surgically removed, and the histopathological examination confirms it to be simple adenocarcinoma
• CLDN18.2 positivity: Provide sufficient tissue markers for Claudin18.2 immunohistochemistry testing. Claudin18.2 immunohistochemistry expression ≥ 10% is confirmed as positive, and\<10% is recorded as negative
• According to RECIST v1.1 standard, there should be at least one measurable lesion
• ECOG physical state ≤ 1
• Expected lifespan\>3 months
• Adequate renal function: creatinine (Cr) ≤ 1.5 x upper limit of normal (ULN) and glomerular filtration rate (GFR) ≥ 60mL/min/1.73 m2;
• Sufficient liver function: Total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 2.5 × ULN (if there is liver metastasis, AST and ALT ≤ 5 × ULN, total bilirubin ≤ 2.5 × ULN);
• Adequate bone marrow reserve: Platelet count (PLT) ≥ 100 × 109/L, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, hemoglobin ≥ 9 g/dL (no adjuvant therapy such as EPO, G-CSF, or GM-CSF has been received within 14 days, and no blood transfusion including red blood cells and platelets has been received at least 7 days before the first administration); Prothrombin time/activated partial thromboplastin time (PT/PTT)\<1.5 x ULN;
• Male or female aged ≥ 18 years old.

You may not qualify if:

• Known HER2 positive gastric cancer/adenocarcinoma of the gastroesophageal junction. HER2 positivity refers to HER2 amplification that requires confirmation from ISH if the HER2 immunohistochemistry test result is 3+and the immunohistochemistry test result is 2+
• Has undergone major surgery or radiation therapy within 4 weeks prior to enrollment;
• Active, known or suspected autoimmune diseases
• Congestive heart failure or symptomatic coronary artery disease within 3 months prior to enrollment
• A cerebrovascular accident occurred within the past 6 months
• Clinically significant bleeding, bleeding events, or thromboembolic diseases occur within 6 months
• History of intestinal perforation
• Have a history of (non infectious) pneumonia requiring steroid treatment or currently suffer from pneumonia
• Severe impairment of lung function or history of interstitial lung disease
• Diagnosed with concurrent malignant tumors within the past 2 years (except for fully treated non melanoma skin cancer, superficial bladder transitional cell carcinoma, and cervical carcinoma in situ \[CIS\]) or any currently active malignant tumor
• Previous or current evidence suggests that there may be confusion with the research results, interference with the participant\'s participation in the entire study process, any conditions, treatments, or laboratory abnormalities, or the researcher believes that participating in this study is not in the best interest of the participant
• Pregnancy test positive within 7 days before the first administration, or women of childbearing age who are in lactation period
• Individuals with known mental illnesses or disorders that may affect trial compliance
• Subjects who take systemic corticosteroids (\>10 mg daily prednisone equivalent) or other systemic immunosuppressive drugs (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor drugs) within 2 weeks prior to the first medication are allowed to use local, ocular, intra-articular, intranasal, and inhaled corticosteroids
• Subjects with a known history of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Guillain Barre syndrome, multiple sclerosis, or glomerulonephritis, excluding autoimmune hypothyroidism treated with stable dose hormone replacement therapy

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Study Officials

• Tianshu Liu, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yiyi Yu, Doctor

CONTACT

+86 138 1673 0912; yu.yiyi@zs-hospital.sh.cn

Mengling Liu, Doctor

CONTACT

+86 153 1615 8393; liu.mengling@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

Model Details: The study is divided into a safety lead-in phase and an expansion phase. The safety lead-in phase will evaluate the dose-limiting toxicity (DLT) of the LM-302 combined with cadonilimab and capecitabine regimen in patients with unresectable, recurrent, or metastatic CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. Based on the safety data obtained from the lead-in phase, the expansion phase will determine the drug dosage and assess the efficacy and safety of the LM-302 combined with cadonilimab and capecitabine regimen in the same patient population.

Study Record Dates

• First Submitted: September 4, 2024
• First Posted: September 19, 2024
• Study Start: July 31, 2024
• Primary Completion: July 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

CN (1)