Pemigatinib Combined With Durvalumab for the Safety and Efficacy in Second-Line Treatment of Biliary Tract Cancer: A Single-Arm, Multicenter Phase II Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Pemigatinib and Durvalumab
- Conditions
- Biliary Tract Carcinoma
- Sponsor
- Eastern Hepatobiliary Surgery Hospital
- Enrollment
- 38
- Primary Endpoint
- Objective Response Rate
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
This study is a single-arm, multicenter Phase II clinical trial designed to preliminarily assess the safety and efficacy of the combination therapy of pemigatinib and durvalumab in the second-line treatment of patients with advanced malignant biliary tract cancer.
The study anticipates enrolling 38 participants characterized by the following criteria: 1) A confirmed diagnosis of advanced, metastatic, or unresectable biliary tract cancer by histopathological examination; 2) Presence of FGFR2 fusion or rearrangement confirmed by testing; 3) Prior receipt of first-line treatment for biliary tract cancer.
The primary questions the study aims to address are:
- Can the combination of pemigatinib and durvalumab improve the prognosis of participants with previously treated biliary tract cancer (BTC)?
- What is the safety profile of the treatment with pemigatinib and durvalumab?
Participants will receive:
- Oral administration of 13.5 mg pemigatinib once daily, in combination with durvalumab 1500 mg via intravenous infusion.
- Follow-up visits will be scheduled every 6 weeks.
Investigators will observe and document the objective tumor response rate of the participants, as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and adverse events.
Investigators
Shen Feng
Chairman of Clinical Research Institute
Eastern Hepatobiliary Surgery Hospital
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years, men and women;
- •ECOG performance status of 0-1;
- •Histologically confirmed advanced gallbladder cancer or cholangiocarcinoma patients who have received one prior line of therapy;
- •Adult patients with advanced, metastatic, or unresectable cholangiocarcinoma or gallbladder cancer confirmed to have FGFR2 fusion or rearrangement;
- •Diagnosed with locally advanced disease according to the 8th edition of AJCC, with clinical staging of cT3/4NxM0/1 for gallbladder cancer, intrahepatic cholangiocarcinoma, or hilar cholangiocarcinoma, or cT2N2M0, cT3/4NxM0/1 for distal cholangiocarcinoma based on enhanced CT or MRI;
- •Use of contraception during the study period;
- •Life expectancy ≥3 months;
- •All patients must provide tumor tissue specimens (fresh or paraffin-embedded) for FGFR2 expression analysis before enrollment and after surgery (5 slides within 3 years are required);
- •At least one measurable lesion according to RECIST 1.1 criteria, which has not been irradiated;
- •Within 7 days prior to the first administration of the study drug, the organ function levels of the enrolled patients must meet the following requirements:
Exclusion Criteria
- •Patients who have not received standard first-line treatment for advanced biliary tract tumors;
- •Pregnant or breastfeeding women, and women of childbearing age with positive pregnancy test results at baseline;
- •Patients diagnosed with central nervous system metastasis by CT/MR/PET-CT;
- •Patients who have previously received live vaccine administration or other antitumor treatments such as radiotherapy;
- •Patients who have participated in or are currently participating in other drug or therapy clinical trials within 4 weeks prior to the first administration of the study medication;
- •Patients who have undergone major surgical procedures within 4 weeks prior to the first administration of the study medication or have not recovered from the side effects of such surgery, or patients who have undergone radiotherapy within 2 weeks prior to the first administration of the study medication;
- •Patients with any primary immunodeficiency, active autoimmune disease, or history of autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, vitiligo, patients with a history of asthma who have completely resolved in childhood and do not require any intervention in adulthood may be included; patients with asthma requiring medical intervention with bronchodilators are excluded;
- •Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation, and patients currently using immunosuppressants or corticosteroids for immunosuppressive purposes (dosage \>10mg/day prednisone or other equivalent corticosteroids) and still in use within 2 weeks prior to enrollment;
- •Patients with other malignancies within the past 5 years, except for cured skin basal cell or squamous cell carcinoma, superficial bladder cancer, early prostate cancer, in situ cervical cancer, or breast cancer;
- •Patients who have received hematopoietic growth factors within 1 week prior to the first administration of the study medication, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc.;
Arms & Interventions
Pemigatinib and Durvalumab
The combination of targeted drugs and immunotherapies has demonstrated their clinical value in the treatment of various tumors, and pemigatinib and durvalumab are such a promising combination product. In this combination, Pemigatinib is used according to the following rules:13.5mg, oral administration, once daily, swallow the entire tablet with or without food. Take for 2 weeks and then discontinue for 1 week. Durvalumab is used as this: 1500mg, intravenous infusion, once every three weeks. Each infusion should take over 60 minutes.
Intervention: Pemigatinib and Durvalumab
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: From enrollment to the end of treatment at 8 weeks
Objective response rate is defined as the proportion of subjects who achieved a complete response (CR; disappearance of all target lesions) or a PR (\> 30% decrease in the sum of the longest diameters of target lesions) based on RECIST v1.1. Clinical response will be determined by an independent radiological review committee.
Secondary Outcomes
- Progression-free Survival (PFS)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
- Disease Control Rate (DCR)(From enrollment to the end of treatment at 8 weeks)
- Overall survival (OS)(From date of randomization until the date of death from any cause, whichever came first, assessed up to 36 months)
- Adverse Event (AE)(From enrollment to the end of treatment at 8 weeks)