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
The antibody-drug conjugate (ADC) targeting CLDN18.2 exerts its anti-tumor effects through multiple mechanisms, including direct cytotoxicity to CLDN18.2-positive tumor cells via the delivery of a potent small-molecule toxin, a bystander effect that induces cytotoxicity in adjacent CLDN18.2-negative tumor cells, and the activation of the immune system through antibody-dependent cellular cytotoxicity (ADCC). The combination of this ADC with immune checkpoint inhibitors holds potential for synergistic anti-tumor activity. LM-302, an ADC specifically targeting CLDN18.2 and comprising a monoclonal antibody conjugated to MMAE, has demonstrated favorable efficacy and safety profiles in both preclinical and clinical studies for CLDN18.2-expressing gastrointestinal malignancies, including gastric and gastroesophageal junction adenocarcinomas. The combination of LM-302 with immune checkpoint inhibitors may offer enhanced clinical benefits for patients with advanced gastric cancer. This clinical study aims to evaluate the efficacy and safety of LM-302 (ADC targeting Claudin18.2) in combination with cadonilimab (a bispecific antibody targeting PD-1 and CTLA-4) and capecitabine as a first-line treatment in patients with unresectable, recurrent, or metastatic CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
LM-302: 1.8mg/kg ivgtt d1, q2w; Canonilimab: 6mg/kg ivgtt d1, q2w; Capecitabine: 1000mg/m\^2 po bid d1-10, q2w.
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGDose limiting toxicity (DLT)
DLT is defined as a toxicity (adverse event at least possibly related to LM302) occurring during the DLT observation period
Time frame: 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
Time frame: From enrollment until 6 months after the last participant discontinues treatment, up to approximately 42 months
Overall Survival (OS)
OS was defined defined as the time from date of randomization until death from any cause.
Time frame: From enrollment until 6 months after the last participant discontinues treatment, up to approximately 42 months.
Objective response rate (ORR)
defined as the proportion of participants who achieve a best response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Investigator.
Time frame: From start of treatment to date of documented disease progression, up to approximately 42 months
Duration of response (DoR)
defined time from the initial response (CR or PR) until documented tumor progression or death from any cause and based on Investigator assessment.
Time frame: From start of treatment to date of documented disease progression, up to approximately 42 months
Disease control rate (DCR)
defined as the proportion of participants who achieved CR, PR, or stable disease (SD) for a minimum of 6 weeks during study treatment, based on Investigator assessment.
Time frame: From start of treatment to date of documented disease progression, up to approximately 42 months
. AE and SAE
Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0
Time frame: : From signing the ICF until 28 days after EOT or accept other anti-cancer therapy,up to 40 days after last study dose
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