BTC
Conditions
Keywords
lparomlimab and Tuvonralimab injection, GemOX, Lenvatinib
Brief summary
The primary objective is to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab Injection (QL1706, an Anti-PD-1/CTLA-4 Combined Antibody) combined with GemOX and lenvatinib as conversion therapy for Initially Potentially Resectable intrahepatic cholangiocarcinoma and gallbladder cancer.
Detailed description
This single-arm, single-center clinical study aims toevaluate the efficacy and safety of Iparomlimab and Tuvonralimab Injection (QL1706, an Anti-PD-1/CTLA-4 Combined Antibody) combined with GemOX and lenvatinib as conversion therapy for Initially Potentially Resectable intrahepatic cholangiocarcinoma and gallbladder cancer. This study consists of three phases: screening, treatment, and follow-upEfficacy evaluation and safety monitoring should be performed throughout the study.
Interventions
DRUGIparomlimab and Tuvonralimab Injection combined with GemOX and lenvatinib
Iparomlimab and Tuvonralimab Injection:5 mg/kg, intravenous infusion on Day 1 of each 3-week cycle (q3w); for 4 to 6 cycles. Lenvatinib: 8-12 mg, orally once daily (qd). The dose is determined by body weight:8 mg po qd for body weight \< 60 kg;12 mg po qd for body weight ≥ 60 kg GemOX Regimen: Oxaliplatin: 85 mg/m², intravenous infusion on Day 1 of each 3-week cycle (q3w); for a maximum of 6 cycles. Gemcitabine: 1000 mg/m², intravenous infusion on Day 1 and Day 8 of each 3-week cycle (q3w); for a maximum of 6 cycles. Postoperative Treatment for Patients with Successful Conversion: Iparomlimab and Tuvonralimab Injection: 5 mg/kg, intravenous infusion on Day 1 of each 3-week cycle (q3w); for 8 cycles. For Patients without Successful Conversion: Subsequent treatment regimens will be determined by the investigator.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years, male or female. * Histologically or cytologically confirmed diagnosis of locally advanced or potentially resectable intrahepatic cholangiocarcinoma or gallbladder cancer, defined as T2b-T4 or N1 M0 according to the AJCC 8th edition. * Expected life expectancy ≥ 12 weeks. * No prior systemic treatment for biliary tract cancer before the first dose of study medication. * At least one measurable lesion as defined by RECIST 1.1 criteria. * ECOG Performance Status of 0 or 1. * Adequate organ function, without severe dysfunction of the hematologic, cardiac, pulmonary, hepatic, renal, bone marrow, or immune systems. * Laboratory tests meeting the following requirements: Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days before enrollment and voluntarily use adequate contraception during the observation period and for 8 weeks after the last dose of the study drug. For men, they must be surgically sterile or agree to use adequate contraception during the observation period and for 8 weeks after the last dose of the study drug. * Patient voluntarily participates and provides written informed consent. * Good compliance is anticipated, allowing for efficacy and adverse event follow-up per the protocol.
Exclusion criteria
* The subject has received any prior antitumor therapy or any investigational anticancer agents. * Presence of any active autoimmune disease or a history of autoimmune diseases (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism \[may be enrolled if stable on hormone replacement therapy\]). Patients with childhood asthma that has completely resolved in adulthood without any intervention, or vitiligo, may be enrolled. Patients requiring medical intervention with bronchodilators are not eligible. * Known congenital or acquired immunodeficiency, such as Human Immunodeficiency Virus (HIV) infection. * Uncontrolled cardiac clinical symptoms or diseases, e.g., NYHA Class II or above heart failure, unstable angina, myocardial infarction within 1 year, or patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention. * Severe concurrent infection within 4 weeks prior to the first dose (e.g., requiring intravenous antibiotics, antifungals, or antivirals), or unexplained fever \>38.5°C during screening/prior to the first dose. * Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. * Administration of a live attenuated vaccine within 4 weeks prior to the first dose or planned administration during the study period. * History of or concurrent other malignant tumors within the past 5 years (except for adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, and ovarian cancer). * Gastrointestinal bleeding event or active hemoptysis within 28 days prior to the first dose. * Gastric or esophageal varices requiring treatment. * Active malignant tumors within 36 months prior to enrollment. * Known allergy to any of the investigational drug components. * Poorly controlled psychiatric disorder. * Presence of superior mesenteric vein tumor thrombus, metastasis to group 16 lymph nodes, or distant metastasis to other organs / biological factors: peritoneal metastasis, direct invasion to adjacent organs, etc. / involvement of organs (pancreas, stomach, duodenum, colon) that cannot be resected en bloc. * Any other condition deemed by the investigator as unsuitable for enrollment. This includes, but is not limited to, pre-existing central nervous system metastases, severe laboratory abnormalities, or familial/social factors that could compromise the subject's safety, or data/sample collection. * Patients with extensive liver metastases involving the entire liver.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| R0 Resection Rate | up to 12 month |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | up to 12 month | the percentage of participants in the analysis population who had a CR(Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) usingRECIST 1.1 based on investigator assessment. |
| Progression-Free Survival | up to 12 month | PFS was defined as the time from first dose of study treatment to the firstdocumented PD per REClST 1.1 by investigator assessment, or death due to any cause, whicheveroccurred first. |
| Conversion Rate | up to 12 month | — |
| Overall survival | up to 36 month | OS was defined as the time from the first dose of study drug to death due to any cause. |
| Adverse Events | up to 36 month | An AE was defined as any untoward medical occurrence in a pharmaceutical productwhich does not necessarily have to have a causal relationship with this treatment. |
| pathological Complete Response | up to 12 month | — |
Countries
China
Contacts
Primary ContactWei Zhang
Backup ContactWen X Liu
Outcome results
None listed