A Phase II Multicenter, Single Arm Study of Oral BGJ398 in Adult Patients With Advanced or Metastatic Cholangiocarcinoma With FGFR2 Gene Fusions or Other FGFR Genetic Alterations Who Failed or Are Intolerant to Platinum-based Chemotherapy
Description
Brief Summary
This is a multi-center, open label, single arm phase II study evaluating BGJ398
(infigratinib) anti-tumor activity in advanced or metastatic cholangiocarcinoma patients with
fibroblast growth factor receptor (FGFR) genetic alterations.
Detailed Description
Adult patients with histologically or cytologically confirmed advanced or metastatic
cholangiocarcinoma with FGFR2 gene fusions or translocations or other FGFR genetic
alterations have been enrolled. Subjects must have received at least one prior regimen
containing gemcitabine with or without cisplatin for advanced/metastatic disease. Subjects
should have had evidence of progressive disease following their prior regimen or if prior
treatment was discontinued due to toxicity must have continued evidence of measurable
disease. Up to approximately 160 adult patients over age 18, both male and female were
planned for enrollment.
Three cohorts of subjects comprise the study population:
Cohort 1: subjects with FGFR2 gene fusions (ie, fusions or rearrangements [formerly
translocations]).
Cohort 2: subjects with FGFR genetic alterations other than FGFR2 gene fusions or
rearrangements.
Cohort 3: subjects with FGFR2 gene fusions or rearrangements who have received a prior FGFR
inhibitor.
All subjects received oral BGJ398 (infigratinib), once-daily, on a three weeks on (21 days),
one week off (7 days) schedule. One treatment cycle consists of 28 days.
Notes:
Cohort 1 was pre-specified as the primary analysis population. Results of these analyses were
previously disclosed (posted 22 June 2022). There were no additional efficacy or safety
endpoints to assess in Cohort 1 after primary completion (01 March 2021).
Cohorts 2 and 3 were added at protocol amendment (PA) 4 to support only exploratory efficacy
objectives of the study. These cohorts were ongoing the time of primary completion (01 March
2021). After interim review of the data from these cohorts (as permitted by the protocol)
only limited efficacy was observed and the sponsor terminated the study early. Therefore, a
formal efficacy analysis was not performed for Cohorts 2 and 3. However, baseline
characteristics and safety data were analyzed.
Phase
Phase 2 - takes the treatment one step further, assessing the activity of a particular therapy in a disease, often building upon leads from the Phase I trial. While patients are generally required to be previously untreated, participation in a Phase II trial doesn't usually preclude the patient from getting the standard treatment after they've received the investigational agent. At best they are allowed to get a new drug they wouldn't be able to get otherwise that may turn out to be better for their disease.Inclusion and Exclusion Criteria
- Adult patients with histologically or cytologically confirmed cholangiocarcinoma at the time of diagnosis. Patients with cancers of the gallbladder or ampulla of Vater are not eligible.
- Patients must have received at least one prior regimen containing gemcitabine with or without cisplatin for advanced/ metastatic disease. Patient should have evidence of progressive disease following prior regimen, or if prior treatment discontinued due to toxicity must have continued evidence of measurable or evaluable disease.
- Prior or current treatment with a MEK inhibitor (all Cohorts), BGJ398 (infigratinib) (all Cohorts), or selective FGFR inhibitor (Cohorts 1 and 2 only).
- insufficient organ function
- Absolute Neutrophil Count (ANC) < 1,000/mm3 [1.0 x 10^9/L]
- Platelets < 75,000/mm3 [75 x 10^9/L]
- Hemoglobin < 109.0 g/dL
- Total bilirubin > 1.5x upper limit of normal (ULN)
- Aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/glutamic pyruvic transaminase (ALT/SGPT) > 2.5x ULN (AST and ALT > 5x ULN in the presence of liver metastases)
- Serum creatinine > 1.5x ULN and a calculated or measured creatinine clearance < 45 mL/min
- Inorganic phosphorus outside of normal limits
- Total and ionized serum calcium outside of normal limits Other protocol-defined inclusion/exclusion criteria may apply.
Sites
-
California
- USC/Kenneth Norris Comprehensive Cancer Center Onc Dept, Los Angeles, California, 90033
- University of California at Los Angeles UCLA SC, Los Angeles, California, 90095
- University of California San Francisco Oncology, San Francisco, California, 94101
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Illinois
- NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Onc Dept, Chicago, Illinois, 60611
-
Germany
- Novartis Investigative Site, Heidelberg, 69120
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Taiwan
- Novartis Investigative Site, Tainan, 70403
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France
- Novartis Investigative Site, Rennes Cedex, 35062
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