Prospective, Single-arm, Multicenter Phase II Study of Evaluation of the Efficacy and Safety of Pemigatinib Combined With PD-1 Inhibitor in First-line Treatment of Unresectable or Metastatic Intrahepatic Cholangiocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Pemigatinib
- Conditions
- Carcinoma
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Prospective, single-arm, phase II study with multicenter participation. The objective of this study is to evaluate the efficacy and safety of pemigatinib combined with PD-1 inhibitor as first-line treatment for patients with advanced unresectable or metastatic intrahepatic cholangiocarcinoma.
Detailed Description
The study will be divided into two phases. The first phase is the safety import phase, in which three subjects with intrahepatic cholangiocarcinoma will be enrolled to receive a Scheduled dose of pemigatinib for one course of treatment， If the initial three subjects didn't develop DLT during the 21-day observation period, the dose will be considered tolerable and the study will proceed to Part II, otherwise, the dose will be adjusted and the evaluation will continue according to the above criteria. A total of 30 subjects will be enrolled in Phase II of the study, and all screening-qualified subjects will receive pemigatinib combined with PD-1 inhibitor. pemigatinib and PD-1 inhibitors will be administered at established doses according to a regimen until progressive disease, intolerable toxicity, or informed consent form has been withdrawn. PD-1 inhibitors will be administered for a maximum of 24 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Local advanced, recurrent, or metastatic cholangiocarcinoma confirmed by histology or cytology and judged as unresectable by imaging and clinical diagnosis;
- •Have not received systematic treatment in the past;
- •The existence of FGFR2 fusion/rearrangement was confirmed by gene detection;
- •Male or female aged ≥ 18 years;
- •According to RECIST v1.1, there is at least one measurable target lesion. And the target lesion has not received local treatment;
- •No other anti-tumor treatment was received within 4 weeks before the first use of the study drug;
- •Life expectancy ≥ 12 weeks;
- •Eastern Oncology Collaboration group (ECOG) physical condition (PS) score 0-1;
- •Having sufficient organ and bone marrow function reserve, which is defined as follows:(1)Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelet count (PLT) ≥ 80 × 109/L Hemoglobin content (HGB) ≥ 9.0 g/dL. G-CSF, GM-CSF, red blood cell infusion, and platelet infusion were not used within 14 days before the examination; (2)Liver function requirement for patients without liver metastasis: serum total bilirubin (TBIL) ≤ 1.5 × Upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Requirements for patients with liver metastasis or intrahepatic cholangiocarcinoma: serum TBIL ≤ 1.5 × ULN; ALT and AST ≤ 5 × ULN; (3)Renal function: creatinine clearance rate (Ccr) ≥ 50 mL/min (calculated by Cockcroft/Default formula): female: CrCl=(0.85 × (140 - Age) × (Weight)/(72 × Serum creatinine (mg/dL), male: CrCl=(140 age) × (Weight)/(72 × Serum creatinine (mg/dL); (4)Sufficient blood coagulation function, defined as the international standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; If the subject is receiving anticoagulation treatment, it is acceptable as long as PT is within the scope of anticoagulation drugs;
- •Female subjects of reproductive age or male subjects with female sexual partners of reproductive age shall take effective contraceptive measures during the whole treatment period and 6 months after the treatment period.
Exclusion Criteria
- •Previously received selective FGFR inhibitor treatment, excluding pan target inhibitors such as Anlotinib and Lenvatinib
- •Received immunosuppressive drugs within 4 weeks before the first administration of the trial treatment, excluding local glucocorticoids or systemic glucocorticoids of physiological dose by nasal spray, inhalation, or other means (i.e. no more than 10 mg/day prednisone or other glucocorticoids of equivalent dose).
- •Received live attenuated vaccine within 4 weeks before the first administration of the trial treatment or during the study period.
- •Received any other study drug treatment or participated in interventional clinical research 4 weeks before the first administration of the trial treatment;
- •Before the first administration of the trial treatment, there was toxicity caused by previous anti-tumor treatment that was not restored to the level 0 or 1 of the National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI CTCAE Version 5.0) (excluding alopecia, non-clinically significant laboratory abnormalities, and asymptomatic laboratory abnormalities).
- •Active, known or suspected autoimmune disease, or history of autoimmune disease in the past 2 years (patients with vitiligo that do not need systematic treatment, psoriasis, alopecia, or Graves' disease in the past 2 years, hypothyroidism who only need thyroid hormone replacement therapy and type I diabetes who only need insulin replacement therapy can be enrolled).
- •Known history of primary immunodeficiency.
- •Known to have active pulmonary tuberculosis.
- •Known Symptomatic central nervous system metastases and/or carcinomatous meningitis. For patients with brain metastasis who have received treatment in the past, if their condition is stable (no evidence of imaging progress is found at least 4 weeks before the first administration of the trial treatment), and repeated imaging examination proves that there is no evidence of new brain metastasis or enlargement of the original brain metastasis focus, and they do not need steroid treatment at least 14 days before the first administration of the trial treatment, they can participate in the trial. This exception does not include carcinomatous meningitis, regardless of its clinical stability should be excluded.
- •Medical history of other primary malignant tumors, except: (1)malignant tumors that have completely alleviated for at least 5 years before enrollment and do not require other treatment during the study period; (2)Fully treated non-melanoma skin cancer or malignant lentigo without evidence of disease recurrence; (3)Fully treated carcinoma in situ without evidence of disease recurrence.
Arms & Interventions
pemigatinib combined with PD-1 inhibitor
pemigatinib combined with PD-1 inhibitor as first-line treatment within advanced unresectable or metastatic intrahepatic cholangiocarcinoma
Intervention: Pemigatinib
pemigatinib combined with PD-1 inhibitor
pemigatinib combined with PD-1 inhibitor as first-line treatment within advanced unresectable or metastatic intrahepatic cholangiocarcinoma
Intervention: PD-1 Inhibitors
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: 2 years
The proportion of subjects who achieved complete response (CR; all target lesions disappeared) or partial response (PR; the sum of the longest diameter of target lesions decreased by ≥ 30%) according to the RECIST1.1 standard.
Secondary Outcomes
- Disease Control Rate(2 years)
- Progression-Free-Survival(2 years)
- Duration of Response(2 years)
- Overall Survival(2 years)