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NCT02150967

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

Terminated Phase 2 Results posted Last updated 3 July 2023
What this trial tests

Phase 2 trial testing BGJ398 (infigratinib) in Advanced Cholangiocarcinoma in 143 participants. Terminated before completion.

Timeline
23 July 2014
Primary endpoint
1 March 2021
7 February 2022

Quick facts

Lead sponsorQED Therapeutics, a BridgeBio company
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment143
Start date23 July 2014
Primary completion1 March 2021
Estimated completion7 February 2022
Sites37 locations across Italy, Russia, Belgium, Taiwan, United Kingdom, Germany, South Korea, Thailand

Drugs / interventions tested

Conditions studied

Sponsor

QED Therapeutics, a BridgeBio company — full company profile →

Who can join

18 and older, any sex, with Advanced Cholangiocarcinoma or FGFR2 Gene Mutation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) as Assessed by Blinded Independent Central Imaging Review (BICR) Primary · 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.

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 pr

GroupValue95% CI
Cohort 1: FGFR2 Fusions23.115.6 – 32.2
Overall Response Rate (ORR) as Assessed by the Investigator Secondary · 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.

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 additi

GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements32.423.7 – 42.1
Best Overall Response (BOR) Secondary · 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.

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 th

BOR by BICR
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements1
Cohort 1: FGFR2 Fusion/Rearrangements24
Cohort 1: FGFR2 Fusion/Rearrangements66
Cohort 1: FGFR2 Fusion/Rearrangements11
BOR by Investigator
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements0
Cohort 1: FGFR2 Fusion/Rearrangements35
Cohort 1: FGFR2 Fusion/Rearrangements56
Cohort 1: FGFR2 Fusion/Rearrangements11
Disease Control Rate (DCR) Secondary · 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.

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 dia

DCR by BICR
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements84.376.0 – 90.6
DCR by Investigator
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements84.376.0 – 90.6
Progression-Free Survival (PFS) Secondary · 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.

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 a

PFS by BICR
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements7.295.59 – 7.56
PFS by Investigator
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements6.745.55 – 7.56
Overall Survival (OS) Secondary · 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.

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.

GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements11.8610.68 – 14.85
Duration of Response (DOR) Secondary · 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.

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 lesion

DOR by BICR
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements5.553.78 – 7.66
DOR by Investigator
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements7.235.16 – 9.00
Response Onset Secondary · 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.

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 presp

Response onset by BICR
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements3.611.38 – 7.36
Response onset by Investigator
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements1.941.38 – 18.76
Growth Modulation Index (GMI) Secondary · 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.

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.

PFS by BICR
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements1.220.00 – 120
PFS by Investigator
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements1.240.00 – 120
Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on ORR Secondary · 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.

Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Investigator-assessed ORR was obtained from subjects' medical histories to provide a baseline evaluation of their response after historical second-line antineoplastic treatment prior to infigratinib treatment. Investigator-assessed ORR was then calculated in the same subjects after third- or later-line infigratinib therapy. ORR is defined as the percentage (%) of patients with CR or PR, per RECIST (v1.1). RECIST (v1.1) response criteria were as follows: CR: disa

After Second-Line Therapy (Prior to Infigratinib Treatment)
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements00.0 – 6.1
Third or Later-Line Therapy (Infigratinib)
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements28.817.8 – 42.1
Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on PFS Secondary · 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.

Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Investigator-assessed PFS was obtained from subjects' medical histories to provide a baseline evaluation of their response after historical second-line antineoplastic treatment prior to infigratinib treatment. Investigator-assessed PFS was then calculated in the same subjects after third- or later-line infigratinib therapy. Note: The primary efficacy outcome measures were prespecified only for Cohort 1 (FGFR fusions) (disclosed 22 June 2022). Due to early termina

After Second-Line Therapy (Prior to Infigratinib Treatment)
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements5.363.25 – 8.15
Third or Later-Line Therapy (Infigratinib)
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements6.934.76 – 7.59
Retrospective Analysis of Post-second-line Antineoplastic Treatment Outcomes on BOR Secondary · 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.

Post-hoc subgroup assessment of efficacy in those subjects who were receiving infigratinib as a third or later line of treatment. Investigator-assessed BOR was obtained from subjects' medical histories to provide a baseline evaluation of their response after historical second-line antineoplastic treatment prior to infigratinib treatment. Investigator-assessed BOR was then calculated in the same subjects after third- or later-line infigratinib therapy. The endpoint is summarized for the rate of BOR of PD, SD, PR, and CR. Note: The primary efficacy outcome measures were prespecified only for

After Second-Line Therapy (Prior to Infigratinib Treatment)
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements0
Cohort 1: FGFR2 Fusion/Rearrangements0
Cohort 1: FGFR2 Fusion/Rearrangements19
Cohort 1: FGFR2 Fusion/Rearrangements22
Third or Later-Line Therapy (Infigratinib)
GroupValue95% CI
Cohort 1: FGFR2 Fusion/Rearrangements0
Cohort 1: FGFR2 Fusion/Rearrangements17
Cohort 1: FGFR2 Fusion/Rearrangements31
Cohort 1: FGFR2 Fusion/Rearrangements7

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of infigratinib with follow-up of at least 10 months after initial exposure. Data cutoff for Cohort 1 (primary analysis population) was 01 March 2021 (disclosed 22 June 2022). Data cutoff for Cohorts 2 and 3 (exploratory analysis only) was 07 February 2022.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: FGFR2 Fusions
Serious: 35/108 (32%)
Deaths: 93/108
Cohort 2: Other FGFR Genetic Alterations
Serious: 11/25 (44%)
Deaths: 19/25
Cohort 3: FGFR2 Fusions and Prior FGFR Inhibitor
Serious: 2/10 (20%)
Deaths: 7/10

Serious adverse events (66 terms)

ReactionSystemCohort 1: FGFR2 FusionsCohort 2: Other FGFR Genet…Cohort 3: FGFR2 Fusions an…
AnaemiaBlood and lymphatic system disorders
PyrexiaGeneral disorders
HypercalcaemiaMetabolism and nutrition disorders
SepsisInfections and infestations
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
ConstipationGastrointestinal disorders
CholangitisHepatobiliary disorders
CellulitisInfections and infestations
InfectionInfections and infestations
HypophosphataemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
Atrial fibrillationCardiac disorders
TachycardiaCardiac disorders
HypothyroidismEndocrine disorders
DiarrhoeaGastrointestinal disorders
Gastric ulcer haemorrhageGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Noninfective sialoadenitisGastrointestinal disorders
PancreatitisGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
StomatitisGastrointestinal disorders
Intestinal ischaemiaGastrointestinal disorders
AstheniaGeneral disorders
Other adverse events (119 terms — click to expand)

ReactionSystemCohort 1: FGFR2 FusionsCohort 2: Other FGFR Genet…Cohort 3: FGFR2 Fusions an…
HyperphosphataemiaMetabolism and nutrition disorders
StomatitisGastrointestinal disorders
FatigueGeneral disorders
AlopeciaSkin and subcutaneous tissue disorders
Dry eyeEye disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
DysgeusiaNervous system disorders
HypercalcaemiaMetabolism and nutrition disorders
Dry mouthGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Blood creatinine increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Dry skinSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders
Vision blurredEye disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
DyspepsiaGastrointestinal disorders
Nail discolourationSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
HeadacheNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
OnychomadesisSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
PyrexiaGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Weight decreasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
Nail disorderSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
HyponatraemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Anaemia, Pyrexia, Hypercalcaemia, Sepsis, Abdominal pain, Abdominal pain upper, Ascites, Constipation.

Data from ClinicalTrials.gov NCT02150967 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cholangiocarcinoma - evolving concepts and therapeutic strategies.
    Ilyas SI, Khan SA, Hallemeier CL, Kelley RK, et al · · 2018 · cited 1192× · PMID 28994423 · DOI 10.1038/nrclinonc.2017.157
  2. Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis.
    Sia D, Villanueva A, Friedman SL, Llovet JM. · · 2017 · cited 864× · PMID 28043904 · DOI 10.1053/j.gastro.2016.11.048
  3. FGF/FGFR signaling in health and disease.
    Xie Y, Su N, Yang J, Tan Q, et al · · 2020 · cited 588× · PMID 32879300 · DOI 10.1038/s41392-020-00222-7
  4. Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma.
    Javle M, Lowery M, Shroff RT, Weiss KH, et al · · 2018 · cited 519× · PMID 29182496 · DOI 10.1200/jco.2017.75.5009
  5. New Horizons for Precision Medicine in Biliary Tract Cancers.
    Valle JW, Lamarca A, Goyal L, Barriuso J, et al · · 2017 · cited 475× · PMID 28818953 · DOI 10.1158/2159-8290.cd-17-0245
  6. Polyclonal Secondary <i>FGFR2</i> Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma.
    Goyal L, Saha SK, Liu LY, Siravegna G, et al · · 2017 · cited 439× · PMID 28034880 · DOI 10.1158/2159-8290.cd-16-1000
  7. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study.
    Nogova L, Sequist LV, Perez Garcia JM, Andre F, et al · · 2017 · cited 340× · PMID 27870574 · DOI 10.1200/jco.2016.67.2048
  8. 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.
    Javle M, Roychowdhury S, Kelley RK, Sadeghi S, et al · · 2021 · cited 314× · PMID 34358484 · DOI 10.1016/s2468-1253(21)00196-5

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02150967.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing