Trial Title:
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
NCT ID:
NCT06587425
Condition:
Gastric or Gastroesophageal Junction Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Esophageal Neoplasms
Capecitabine
Conditions: Keywords:
CLDN18.2
ADC drug
cadonilimab
Immune Checkpoint Inhibitor
Targeted therapy
Immunotherapy
Chemotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LM-302+Candonilimab+Capecitabine
Description:
LM-302: 1.8mg/kg ivgtt d1, q2w; Canonilimab: 6mg/kg ivgtt d1, q2w; Capecitabine:
1000mg/m^2 po bid d1-10, q2w.
Arm group label:
LM-302+Cadonilimab+Capecitabine
Other name:
ADC-Claudin18.2+AK104+Capecitabine
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
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- Permissible Previous Treatment: Participants with gastric cancer or gastroesophageal
junction cancer who have previously received adjuvant or neoadjuvant treatment and
have experienced clinical disease progression at least 6 months after the last
administration are eligible for inclusion. (Note: The treatment-related toxicity of
oxaliplatin in previous adjuvant or neoadjuvant treatments must be restored to the
National Cancer Institute [NCI] General Terminology Standard for Adverse Events
[CTCAE] v5.0 Level 1 before enrollment)
- 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.
Exclusion Criteria:
- 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
- Known history of human immunodeficiency virus (HIV) infection. Subjects with active
hepatitis B or active hepatitis C. (Unless receiving antiviral therapy for at least
14 days prior to the first study drug administration and passing hepatitis B virus
(HBV) DNA titer testing (not exceeding 500 IU/mL or 2500 copies [cps]/mL) and
hepatitis C virus (HCV) RNA testing (not exceeding the lower limit of the assay),
eligible for inclusion in the trial and willing to continue receiving effective
antiviral therapy during the study period);
- 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
- Individuals with a history of previous immunodeficiency, including those with other
acquired or congenital immunodeficiency diseases, or those with a history of organ
transplantation, allogeneic bone marrow transplantation, or autologous hematopoietic
stem cell transplantation The researcher determined that there are other situations
that are not suitable for participation in this study
- The researcher determined that there are other situations that are not suitable for
participation in this study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhongshan Hospital Fudan University
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Yiyi Yu, Doctor
Phone:
+86 21 6404 1990
Email:
yu.yiyi@zs-hospital.sh.cn
Investigator:
Last name:
Tianshu Liu, Doctor
Email:
Principal Investigator
Investigator:
Last name:
Yiyi Yu, Doctor
Email:
Sub-Investigator
Investigator:
Last name:
Mengling Liu, Doctor
Email:
Sub-Investigator
Start date:
July 31, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Source:
Shanghai Zhongshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06587425
