Trial Title:
LM-108 Antibody Combination With Sintilimab for Locally Advanced or Metastatic Non-Small Cell Lung Cancer
NCT ID:
NCT06479759
Condition:
NSCLC
PD-1
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Antibodies
Immunoglobulins
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LM-108 antibody and sintilimab
Description:
Cohort 1 receive LM-108 monoclonal antibody combined with sintilimab
Arm group label:
Cohort 1
Other name:
Trial group 1
Intervention type:
Drug
Intervention name:
LM-108 antibody and sintilimab and chemotherapy
Description:
Cohort 2 receive LM-108 monoclonal antibody combined with sintilimab and chemotherapy for
4-6 cycles. LM-108 monoclonal antibody combined with sintilimab will be maintained
Arm group label:
Cohort 2
Other name:
Trial group 2
Summary:
The goal of this clinical trial is to investigate the efficacy, safety and tolerability
of LM-108 antibody in combination with sintilimab for patients with locally advanced or
metastatic Non-Small Cell Lung Cancer patients.
Detailed description:
This study is an open-label, multi-cohort, multi-center clinical trial evaluating the
efficacy, safety, and tolerability of LM-108 monoclonal antibody combined with sintilimab
in treatment-naïve or previously treated subjects with locally advanced or metastatic
non-small cell lung cancer (NSCLC). There are two cohorts in the study:(1)Cohort 1: NSCLC
patients who developed secondary resistance after being sensitive to prior treatment with
PD-1 inhibitors (monotherapy or in combination with another systemic therapy) for 6
months or more are eligible for this study.(2)Cohort 2: Patients with locally advanced or
metastatic NSCLC who have not received prior systemic treatment are eligible for this
study.
Subjects in Cohort 1 will receive LM-108 monoclonal antibody combined with sintilimab.
Subjects in Cohort 2 will receive LM-108 monoclonal antibody combined with sintilimab and
chemotherapy for 4-6 cycles. LM-108 monoclonal antibody combined with sintilimab will be
maintained, and the choice of chemotherapy regimen and the duration of use will be
determined by the investigator. Treatment will continue until disease progression,
unacceptable toxicity, initiation of a new anti-tumor therapy, withdrawal of informed
consent, loss to follow-up, death, or other investigator-determined reasons for
discontinuation, whichever occurs first, with a maximum treatment duration of 24 months.
The primary study endpoint is the objective response rate (ORR) assessed by the
investigator based on the Response Evaluation Criteria in Solid Tumors (RECIST) version
1.1.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Obtain written informed consent before implementing any trial-related procedures;
- Aged >= 18 years old;
- Patients with locally advanced (stage IIIB/IIIC), metastatic, or recurrent (stage
IV) NSCLC confirmed by histology or cytology, who are not candidates for surgical
treatment and cannot undergo curative radiotherapy or chemotherapy according to the
8th edition of the TNM staging classification by the International Association for
the Study of Lung Cancer and the American Joint Committee on Cancer;
- Absence of the following gene mutations: EGFR gene, ALK fusion oncogene, ROS1, etc.
For other types of gene mutations, patients without approved targeted therapies are
allowed to be included;
- Cohort 1: Patients with non-small cell lung cancer who have developed acquired
resistance to PD-1 inhibitors (alone or in combination with another systemic
therapy) after being responsive to treatment (for 6 months or more) can participate
in this study. Cohort 2: Patients who have not received any systemic anti-tumor
treatment for advanced/metastatic disease before; for patients who have previously
received platinum-based adjuvant chemo/radiotherapy, neoadjuvant chemo/radiotherapy,
or curative radiotherapy for advanced disease, disease progression occurred more
than 6 months after the last treatment, they can participate in this study;
- The investigator confirms at least one measurable lesion according to RECIST 1.1
criteria;
- Estimated life expectancy >= 3 months;
- ECOG PS: 0-1 score;
- Provide archived tumor tissue (including formalin-fixed paraffin-embedded tissue
blocks containing tumor [preferred] or approximately 15 freshly cut unstained tissue
sections) for confirmation of immunohistochemistry for PD-L1, CCR8, CCL1, FOXP3,
etc. If archived tissue cannot be obtained, subjects must agree to undergo a tumor
biopsy during the screening period;
- Hematological function is sufficient, defined as absolute neutrophil count >=
1.5×10^9 /L, platelet count >= 100×10^9 /L, hemoglobin >= 90g/L (no history of
transfusion within 7 days);
- Liver function is sufficient, defined as total bilirubin level <= 1.5 times the
upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels <= 2.5 times ULN for all patients, or for patients
with liver metastases, AST and ALT levels <= 5 times ULN;
- Renal function is sufficient, defined as serum creatinine <= 1.5 times ULN;
- Coagulation function is sufficient, defined as international normalized ratio (INR)
or prothrombin time (PT) <= 1.5 times ULN; if the subject is receiving anticoagulant
therapy, INR/PT within the range specified by the anticoagulant drug is acceptable;
- Childbearing-age women must have a negative pregnancy test within 7 days before
starting treatment; and reliable contraception measures (such as intrauterine
devices, contraceptive pills, and condoms) should be used within 30 days of the
start and end of the trial. Childbearing-age male subjects should use condoms for
contraception during the trial and for 30 days after the end of the trial;
- Cooperate with regular follow-up visits and comply with the requirements of the
trial.
Exclusion Criteria:
- Prior use of CCR8 drugs or other unapproved investigational drugs or treatments;
- Known history of intolerance to PD-1 inhibitor therapy;
- Receipt of any approved systemic anti-cancer therapy or systemic immunostimulant
treatment within 28 days prior to the start of the study treatment;
- Use of traditional Chinese medicine or immunomodulatory drugs with anti-tumor
indications within the first 2 weeks prior to first dosing;
- History of allergic reactions to any components of the investigational drug;
- Known presence of brain metastases. Patients judged by the investigator to have
stable brain metastases may be enrolled;
- Active hemoptysis, active diverticulitis, intra-abdominal abscess, gastrointestinal
obstruction, or peritoneal metastasis requiring clinical intervention;
- Clinically uncontrollable pleural effusion/ascites (patients who do not require
fluid drainage or have no significant increase in fluid for 3 days may be enrolled);
- Tumor compression of vital organs (such as esophagus) with associated symptoms,
compression of superior vena cava, or invasion of major mediastinal vessels, heart,
etc.;
- Severe comorbidities such as a history of severe pulmonary or cardiac disease, any
arterial thrombosis, embolism, or ischemia occurring within 6 months prior to
enrollment, such as myocardial infarction, unstable angina, cerebrovascular
accident, or transient ischemic attack. History of deep vein thrombosis, pulmonary
embolism, or any other severe thromboembolic event within 3 months prior to
enrollment;
- Receipt of systemic corticosteroids (> 10 mg/day prednisone or equivalent) or other
systemic immunosuppressive agents (including but not limited to prednisone,
dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-tumor necrosis factor [anti-TNF] drugs) within 2 weeks prior to enrollment. The
use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids is
allowed;
- History of autoimmune diseases, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vasculitis associated with antiphospholipid syndrome,
Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple
sclerosis, vasculitis, or glomerulonephritis. Patients with autoimmune-related
hypothyroidism receiving stable doses of thyroid hormone replacement therapy are
eligible to participate in this study. Patients with type 1 diabetes controlled with
a stable insulin regimen are eligible to participate in this study;
- Active systemic infections, including tuberculosis (clinically diagnosed based on
clinical history, physical examination, and radiological findings, as well as TB
tests performed according to local medical practice), hepatitis B (known positive
for HBV surface antigen [HBsAg], and HBV DNA >= 1000 cps/ml or its lower limit of
reference), hepatitis C, or human immunodeficiency virus (HIV antibody positive);
- Known presence of psychiatric disorders or substance abuse that may affect
compliance with trial requirements;
- Recent use of a full therapeutic dose of oral or non-oral anticoagulants or
thrombolytic agents. Prophylactic use of anticoagulants is allowed;
- History, disease, treatment, or laboratory abnormalities that may interfere with
trial results, hinder the subject's full participation in the study, or are deemed
by the investigator to be not in the subject's best interest to participate in the
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Pulmonary Hospital
Address:
City:
Shanghai
Zip:
200000
Country:
China
Status:
Recruiting
Contact:
Last name:
Li Wang, MD
Phone:
1817021997
Email:
leewang8023@126.com
Start date:
January 12, 2024
Completion date:
December 12, 2025
Lead sponsor:
Agency:
Shanghai Pulmonary Hospital, Shanghai, China
Agency class:
Other
Source:
Shanghai Pulmonary Hospital, Shanghai, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06479759
