Clinical trial NCT02150967: A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced Cholangiocarcinoma
FGFR2 Gene Mutation
Keywords: cholangiocarcinoma,
FGFR2 gene fusion,
FGFR genetic alteration
Lead sponsor: QED Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Helsinn Healthcare SA
First posted: 2014-05-30
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion 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.

Exclusion criteria:

* 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.

Primary outcomes:
measure: Overall Response Rate (ORR) as Assessed by Blinded Independent Central Imaging Review (BICR)
timeFrame: Analysis was conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
Secondary outcomes:
measure: Overall Response Rate (ORR) as Assessed by the Investigator
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff for the primary analysis was 01 March 2021.
measure: Best Overall Response (BOR)
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
measure: Disease Control Rate (DCR)
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
measure: Progression-Free Survival (PFS)
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
measure: Overall Survival (OS)
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
measure: Duration of Response (DOR)
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
measure: Response Onset
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
Other outcomes:
measure: Growth Modulation Index (GMI)
timeFrame: Analysis conducted when all subjects in Cohort 1 had the opportunity to be followed for at least 10 months after their initial exposure to infigratinib. Data cutoff 01 March 2021.
Locations:
city: Phoenix
country: United States
facility: QED Investigative Site
state: Arizona
city: Los Angeles
country: United States
facility: QED Investigative Site
state: California
city: Los Angeles
country: United States
facility: QED Investigative Site
state: California
city: San Francisco
country: United States
facility: QED Investigative Site
state: California
city: Boston
country: United States
facility: QED Investigative Site
state: Massachusetts
city: Detroit
country: United States
facility: QED Investigative Site
state: Michigan
city: New York
country: United States
facility: QED Investigative Site
state: New York
city: New York
country: United States
facility: QED Investigative Site
state: New York
city: New York
country: United States
facility: QED Investigative Site
state: New York
city: Columbus
country: United States
facility: QED Investigative Site
state: Ohio
city: Houston
country: United States
facility: QED Investigative Site
state: Texas
city: Brussels
country: Belgium
facility: QED Investigative Site
city: Leuven
country: Belgium
facility: QED Investigative Site
city: Koeln
country: Germany
facility: QED Investigative Site
state: Nordrhein-Westfalen
city: Heidelberg
country: Germany
facility: QED Investigative Site
city: Tuebingen
country: Germany
facility: QED Investigative Site
city: Ancona
country: Italy
facility: QED Investigative Site
state: AN
city: Milano
country: Italy
facility: QED Investigative Site
state: MI
city: Roma
country: Italy
facility: QED Investigative Site
state: RM
city: Seoul
country: Korea, Republic of
facility: QED Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: QED Investigative Site
state: Korea
city: Moscow
country: Russian Federation
facility: QED Investigative Site
city: Volzhskiy
country: Russian Federation
facility: QED Investigative Site
city: Singapore
country: Singapore
facility: QED Investigative Site
city: Singapore
country: Singapore
facility: QED Investigative Site
city: Barcelona
country: Spain
facility: QED Investigative Site
city: Barcelona
country: Spain
facility: QED Investigative Site
city: Madrid
country: Spain
facility: QED Investigative Site
city: Taipei
country: Taiwan
facility: QED Investigative Site
state: Taiwan ROC
city: Zhunan
country: Taiwan
facility: QED Investigative Site
city: Khon Kaen
country: Thailand
facility: QED Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: QED Investigative Site
city: Bangkok
country: Thailand
facility: QED Investigative Site
city: Bebington
country: United Kingdom
facility: QED Investigative Site
city: Birmingham
country: United Kingdom
facility: QED Investigative Site
city: Manchester
country: United Kingdom
facility: QED Investigative Site
city: Nottingham
country: United Kingdom
facility: QED Investigative Site
Study officials:
affiliation: QED Therapeutics
name: QED Therapeutics
role: STUDY_DIRECTOR
References:
citation: Javle M, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Weiss KH, Waldschmidt DT, Goyal L, Borbath I, El-Khoueiry A, Borad MJ, Yong WP, Philip PA, Bitzer M, Tanasanvimon S, Li A, Pande A, Soifer HS, Shepherd SP, Moran S, Zhu AX, Bekaii-Saab TS, Abou-Alfa GK. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):803-815. doi: 10.1016/S2468-1253(21)00196-5. Epub 2021 Aug 3.
citation: Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, Ramanathan RK, Goyal L, Sadeghi S, Macarulla T, El-Khoueiry A, Kelley RK, Borbath I, Choo SP, Oh DY, Philip PA, Chen LT, Reungwetwattana T, Van Cutsem E, Yeh KH, Ciombor K, Finn RS, Patel A, Sen S, Porter D, Isaacs R, Zhu AX, Abou-Alfa GK, Bekaii-Saab T. Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma. J Clin Oncol. 2018 Jan 20;36(3):276-282. doi: 10.1200/JCO.2017.75.5009. Epub 2017 Nov 28.
citation: Borad MJ, Gores GJ, Roberts LR. Fibroblast growth factor receptor 2 fusions as a target for treating cholangiocarcinoma. Curr Opin Gastroenterol. 2015 May;31(3):264-8. doi: 10.1097/MOG.0000000000000171.