A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma

Advanced Cholangiocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02150967
• Other study ID #: CBGJ398X2204
• Secondary ID: 2013-005085-19
• Status: Terminated
• Phase: Phase 2
• Start date: July 23, 2014
• Est. completion date: February 7, 2022

Study information

• Verified date: June 2023
• Source: QED Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 143
• Est. completion date: February 7, 2022
• Est. primary completion date: March 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Cholangiocarcinoma
• Cholangiocarcinoma
• FGFR2 Gene Mutation

Intervention

Drug:
• BGJ398 (infigratinib)
Capsule for oral use

Locations

Country	Name	City	State
Belgium	QED Investigative Site	Brussels
Belgium	QED Investigative Site	Leuven
Germany	QED Investigative Site	Heidelberg
Germany	QED Investigative Site	Koeln	Nordrhein-Westfalen
Germany	QED Investigative Site	Tuebingen
Italy	QED Investigative Site	Ancona	AN
Italy	QED Investigative Site	Milano	MI
Italy	QED Investigative Site	Roma	RM
Korea, Republic of	QED Investigative Site	Seoul	Korea
Korea, Republic of	QED Investigative Site	Seoul	Korea
Russian Federation	QED Investigative Site	Moscow
Russian Federation	QED Investigative Site	Volzhskiy
Singapore	QED Investigative Site	Singapore
Singapore	QED Investigative Site	Singapore
Spain	QED Investigative Site	Barcelona
Spain	QED Investigative Site	Barcelona
Spain	QED Investigative Site	Madrid
Taiwan	QED Investigative Site	Taipei	Taiwan ROC
Taiwan	QED Investigative Site	Zhunan
Thailand	QED Investigative Site	Bangkok
Thailand	QED Investigative Site	Bangkok
Thailand	QED Investigative Site	Khon Kaen	THA
United Kingdom	QED Investigative Site	Bebington
United Kingdom	QED Investigative Site	Birmingham
United Kingdom	QED Investigative Site	Manchester
United Kingdom	QED Investigative Site	Nottingham
United States	QED Investigative Site	Boston	Massachusetts
United States	QED Investigative Site	Columbus	Ohio
United States	QED Investigative Site	Detroit	Michigan
United States	QED Investigative Site	Houston	Texas
United States	QED Investigative Site	Los Angeles	California
United States	QED Investigative Site	Los Angeles	California
United States	QED Investigative Site	New York	New York
United States	QED Investigative Site	New York	New York
United States	QED Investigative Site	New York	New York
United States	QED Investigative Site	Phoenix	Arizona
United States	QED Investigative Site	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
QED Therapeutics, Inc.	Helsinn Healthcare SA

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Korea, Republic of,  Russian Federation,  Singapore,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Growth Modulation Index (GMI)	The GMI is defined as the ratio of PFS (months) during treatment with infigratinib relative to the time (months) to progression (TTP) during treatment with last prior line of therapy.; Subjects served as their own control.; Results are provided for both BICR and Investigator assessment.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) (disclosed 22 June 2022).; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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.
Primary	Overall Response Rate (ORR) as Assessed by Blinded Independent Central Imaging Review (BICR)	ORR is defined as the percentage (%) of subjects with a best overall response of Complete Response (CR) or Partial Response (PR), as per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) scans every 28 days.; RECIST (v1.1) response criteria were as follows: CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.; PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions). Results were previously disclosed (22 June 2022). There are no additional efficacy endpoints to assess for Cohort 1, thus efficacy data were not re-analyzed for the final analysis.; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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	Overall Response Rate (ORR) as Assessed by the Investigator	ORR is defined as the percentage (%) of subjects with a best overall response of CR or PR, evaluated by CT or MRI scans every 28 days.; RECIST (v1.1) response criteria were as follows: CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.; PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) only. These results were previously disclosed (22 June 2022).; There are no additional efficacy endpoints to assess for Cohort 1, thus efficacy data were not re-analyzed for the final analysis.; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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.
Secondary	Best Overall Response (BOR)	BOR is defined as the best overall response a subject achieved during the study before any subsequent antineoplastic therapy. The endpoint is summarized for the rate of BOR of CR, PR, progressive disease (PD), and stable disease (SD), evaluated by CT or MRI scans every 28 days.; RECIST (v1.1) response criteria were as follows: CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.; PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.; PD: at least a 20% increase in the sum of diameters of all target lesions from that of the smallest sum on study and an absolute increase in target lesion of at least 5mm.; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusion)	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.
Secondary	Disease Control Rate (DCR)	DCR is the percentage (%) of subjects with a BOR of CR, PR, or SD, evaluated by CT or MRI scans every 28 days.; Results are based on both BICR and on Investigator assessment.; RECIST (v1.1) response criteria were as follows: CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.; PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) (disclosed 22 June 2022).; There are no additional efficacy endpoints to assess for Cohort 1, thus efficacy data were not re-analyzed for the final analysis.; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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.
Secondary	Progression-Free Survival (PFS)	PFS was calculated as the number of months from the first dose of study drug to the first documented progression or death due to any cause, whichever occurred earlier. Subjects without an assessment of progression or death were censored at the last adequate tumor assessment. For subjects who had an event after =2 missed visits, the subject was censored at the last adequate tumor assessment before the missing visit.; Disease progression was assessed per RECIST (v1.1) and defined as at least a 20% increase in the sum of diameters of all target lesions from that of the smallest sum on study and an absolute increase in target lesion of at least 5mm.; Results are based on both BICR and on Investigator assessment.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) (disclosed 22 June 2022).; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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.
Secondary	Overall Survival (OS)	OS was defined as the time (months) from the date of start of treatment to the date of death due to any cause.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) (disclosed 22 June 2022).; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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.
Secondary	Duration of Response (DOR)	DOR is defined as the time (months) from the initial response to the time of the event; defined as the first documented progression or death due to any cause, whichever was earlier.; Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator.; RECIST (v1.1) response criteria was as follows: CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.; PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) (disclosed 22 June 2022).; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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.
Secondary	Response Onset	Response onset was defined as the time (months) from the first study treatment administration date to the initial response.; Note that results are based on a subgroup of subjects with confirmed responses (CR or PR) as assessed by BICR or by the Investigator.; RECIST (v1.1) response criteria was as follows: CR: disappearance of all target lesions. Any pathological lymph node (whether target or non-target) must have reduction in short axis to <10 mm.; PR: at least a 30% decrease from baseline in the sum of diameters of all target lesions.; Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) (disclosed 22 June 2022).; Due to early termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.	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.