Toripalimab Plus Lenvatinib as Second-line Treatment in Advanced Biliary Tract Cancers: a Single-arm, Non-randomized, Single-center Clinical Trial and Biomarker Study
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab plus Lenvatinib
- Conditions
- Advanced Biliary Tract Cancer
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 44
- Locations
- 1
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The investigators design a phase II clinical study to explore the efficacy and safety of toripalimab plus lenvatinib as a second-line treatment in patients with advanced biliary tract cancers and to analyze potential biomarkers of therapeutic response.
Detailed Description
This phase II trial is a single-arm, non-randomized and single-center clinical study. It is estimated that 44 patients who met the study criteria will be enrolled in 2 years and treated with toripalimab plus lenvatinib in PUMCH. The investigators will follow up and collect subjects' data each month to evaluate the efficacy and safety of treatment, including overall survival and time to progression, until disease progression or death. Interim analysis and final analysis will be conducted when collecting data from 20 and 44 subjects, respectively in this trial. Histopathology and multi-omics data analysis will be used to explore potential biomarkers of treatment response. Study Type: Interventional. Masking: Open Label.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must meet all of the following criteria
- •Subjects volunteer to participate in the study and agree to sign the informed consent with good compliance and follow-up.
- •Subjects are 18 years old or older when signing the informed consent and gender is not limited.
- •Subjects were diagnosed with advanced biliary tract cancers by imaging and histological examination, including intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, common bile duct cancer and gallbladder cancer. Advanced biliary tract cancers refer to unresectable, recurrent, locally advanced and metastatic lesions which are defined as stage IIIA or above according to the 8th AJCC stage system.
- •The disease is not suitable for radical surgery and/or topical treatment, or disease progression occurs after surgery and/or local treatment, including lesion resection, ablation, transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiotherapy at least 4 weeks before the baseline assessment. All acute toxic effects of local treatment must be ≤ CTCAE 5.0 Level
- •Patients are intolerant or fail after first-line systemic treatment (gemcitabine or platinum based regimen) and require palliative treatment. The first-line system treatment failure was ≥ 1 month before enrollment in this study (signing informed consent) and adverse events are controlled (NCI-CTCAE ≤ Grade Ⅰ). i) Definition of systemic treatment: Gemcitabine or platinum based regimen for more than 1 cycle. Adjuvant chemotherapy based on gemcitabine or platinum is considered as first-line treatment if recurrence occur during or after 6 months adjuvant chemotherapy sequential to tumor resection. ii) Definition of treatment failure: Disease progression occur during treatment or in 6 months after the last cycle. iii) Definition of intolerance: Grade ≥IV hematologic toxicity; grade ≥III toxicity of liver, kidney and skin; grade ≥ II toxicity of heart, lung and brain.
- •Prior treatment must not include lenvatinib, PD-1 / PD-L1 antibodies or molecular targeted therapy for ≥ 14 days.
- •At least one measurable lesion (according to RECIST version 1.1): the measurable lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in spiral CT scan.
- •Blood pressure is controlled \<= 150/90 mmHg with no more than 3 antihypertensive drugs.
- •The ECOG score is 0-1 within 1 week before enrollment.
Exclusion Criteria
- •Subjects with one or more than one of the following criteria should be excluded
- •Patients meet with any of the following condition: Suitable for radical surgery; Or, without an assessment lesion after radical surgery; Or, never receive any first line treatment.
- •Patients who received first-line chemotherapy within 1 month when participating in the study.
- •Already known to be allergic or intolerant to recombinant humanized PD-1 monoclonal antibody drugs (or components) or lenvatinib.
- •Previously received with lenvatinib, or any anti-vascular endothelial growth factor (VEGF) or VEGF receptor targeted drug, or any anti-PD-1, anti-PD-L1 or anti-PD-L2 or CTLA-4 drug, including antibodies involved in JS001 clinical studies.
- •ECOG score ≥ 2 points.
- •Hepatic encephalopathy.
- •Histopathological result show mixed liver cancer, squamous cell carcinoma or sarcoma cell component.
- •More than 2 organs metastasis, including liver, lung, bone and brain.
- •pregnant women (positive pregnancy test before taking the drug) or lactating women.
Arms & Interventions
Toripalimab Plus Lenvatinib
Toripalimab (Shanghai Junshi Biosciences Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody. Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.
Intervention: Toripalimab plus Lenvatinib
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: two years
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.
Rate of adverse events (AE)
Time Frame: two years
the incidence rate of any adverse events related with treatment drugs and details include adverse events type, frequency and severity.
Secondary Outcomes
- Progression-free Survival (PFS)(six months)
- Clinical benefit rate (CBR)(two years)
- Progression free survival rate(6 months)
- Stable Disease (SD)(two years)
- Overall Survival (OS)(two years)
- 6-months and 1-year mortality rate(one year)