Pemigatinib Combined With Durvalumab for Previously Treated Biliary Tract Carcinoma

NCT06530823 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: EHBHKY2024-H018-P001
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

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:

1. 1.Can the combination of pemigatinib and durvalumab improve the prognosis of participants with previously treated biliary tract cancer (BTC)?
2. 2.What is the safety profile of the treatment with pemigatinib and durvalumab?
3. 3.Oral administration of 13.5 mg pemigatinib once daily, in combination with durvalumab 1500 mg via intravenous infusion.
4. 4.Follow-up visits will be scheduled every 6 weeks.

Conditions

Biliary Tract Carcinoma; Cholangiocarcinoma

Keywords

biliary tract carcinoma; cholangiocarcinoma; FGFR mutation; targeted thearpy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  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.

  From enrollment to the end of treatment at 8 weeks

Secondary Outcomes (4)

• 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

Study Arms (1)

Pemigatinib and Durvalumab

EXPERIMENTAL

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.

Drug: Pemigatinib and Durvalumab

Interventions

Pemigatinib and Durvalumab DRUG

Pemigatinib combined with Durvalumab Pemigatinib: 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: 1500mg, intravenous infusion, once every three weeks. Each infusion should take over 60 minutes.

Pemigatinib and Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Hematopoietic function: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count (PLT) ≥ 100×10\^9/L, hemoglobin (Hb) ≥90g/L, and no blood transfusion or component blood transfusion within 14 days prior to testing;
• Hepatic function: Serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (APK) ≤2.5 times ULN, serum creatinine ≤1.5 times ULN and creatinine clearance (based on the Cockcroft-Gault formula) ≥50mL/min, serum albumin (ALB) ≥30g/L, Child-Pugh class A;
• Coagulation function: For patients not receiving anticoagulant therapy, international normalized ratio (INR), activated partial thromboplastin time (APTT) ≤1.5 times ULN; patients receiving anticoagulant therapy should maintain therapeutic levels of anticoagulants;
• Thyroid function: Thyroid-stimulating hormone (TSH) ≤1×ULN, if TSH \>1×ULN, free T3 (FT3) and free T4 (FT4) levels should also be assessed, and if normal, the patient may be enrolled;
• Renal function: Urine protein ≤1+. If urine protein \>1+, a 24-hour urine protein test is required, and the total amount must be ≤1 gram for enrollment;

You may not qualify if:

• 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.;
• Patients with positive HIV antibodies or syphilis antibodies, and patients with active hepatitis B or C;
• Known allergies to recombinant humanized PD-L1 monoclonal antibody drugs and their components;
• Patients with symptomatic pleural effusion, pericardial effusion, or ascites requiring clinical treatment;
• Patients with severe cardiovascular diseases within the last 12 months, such as clinically significant coronary heart disease, NYHA≥II congestive heart failure, uncontrolled arrhythmias, myocardial infarction;
• Within 6 months prior to the first administration of the study medication, the following conditions have occurred: deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmias or angina; percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; cerebrovascular accident, transient ischemic attack, cerebral embolism.

Sponsors & Collaborators

• Eastern Hepatobiliary Surgery Hospital: lead

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

pemigatinib; durvalumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Feng Shen, MD. & PhD.

CONTACT

8616628552926; shenfengdfgd@163.com

Ruiliang Ge, MD

CONTACT

8613917899978; shenhaochina@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman of Clinical Research Institute

Study Record Dates

• First Submitted: July 23, 2024
• First Posted: July 31, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share