Advanced Cholangiocarcinoma, FGFR2 Gene Mutation
Conditions
Keywords
cholangiocarcinoma, unresectable cholangiocarcinoma, metastatic cholangiocarcinoma, fibroblast growth factor receptor inhibitor, FGFR2, FGFR2 gene fusions/translocations, BGJ398
Brief summary
Infigratinib is an oral drug which selectively binds to fibroblast growth factor receptor (FGFR) 2 and is being developed to treat participants with FGFR2 mutated cholangiocarcinoma. The purpose of the study is to evaluate the efficacy and safety of the investigational agent oral infigratinib vs standard of care chemotherapy (gemcitabine plus cisplatin) in first-line treatment of participants with unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion/rearrangement. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.
Interventions
DRUGBGJ398
Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.
DRUGGemcitabine
Gemcitabine 1000 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.
DRUGCisplatin
Cisplatin 25 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.
Sponsors
QED Therapeutics, a BridgeBio company
Helsinn Healthcare SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma are not eligible * Have written documentation of local laboratory or central laboratory determination of a known or likely activating FGFR2 fusion/rearrangement from a sample collected before randomization * Have an archival tumor tissue sample available with sufficient tumor content for FGFR2 fusion/rearrangement molecular testing by the central laboratory. However, if an archival tumor tissue sample is not available, or does not meet requirements for central testing a newly obtained (before randomization) tumor biopsy may be submitted instead. If a prestudy written documentation of FGFR2 fusion/rearrangement in tumor tissue is available from the central laboratory, an additional tumor sample does not need to be submitted. * Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Are able to swallow and retain oral medication * Are willingness to avoid pregnancy or father children
Exclusion criteria
* Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma, with following exceptions 1. Prior neoadjuvant or adjuvant therapy is permitted if completed \> 6 months after the last dose of neoadjuvant or adjuvant therapy. 2. One cycle of gemcitabine-based chemotherapy for locally advanced or metastatic cholangiocarcinoma is permitted before randomization * History of a liver transplant * Received previously or currently is receiving treatment with a mitogen activated protein kinase kinase (MEK) or selective FGFR inhibitor * Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (such as, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection). * Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc. * History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification * Current evidence of corneal or retinal disorder/keratopathy * Receiving and continued treatment or are planning to receive agents or consuming foods that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration * Clinically significant or uncontrolled cardiac disease * Recent (≤ 3 months prior to first dose of study drug) transient ischemic attack or stroke * Severe hearing loss * Severe neuropathy * History of another primary malignancy within 3 years except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer or other curatively treated malignancy that is not expected to require treatment * Pregnant or breastfeeding * Have known microsatellite instability-high (MSI-H) disease and the decision is made by the treating investigator that an alternative, non-study therapy is warranted according to standard of care. * Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents, infigratinib, or their excipients * Have any contraindication to cisplatin or gemcitabine treatment according to local labeling or standard institutional practice. * Have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug. * Have received a live vaccine within 30 days before the first dose of study drug or are planning to receive a live vaccine during participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (Central Imaging Assessment) | From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment. | Defined as the time from randomization until date of disease progression by blinded independent central imaging assessment (Response Evaluation Criteria in Solid Tumors \[RECIST\] v. 1.1) or death, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin | From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment. | Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first. |
| Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment | From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). | ORR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR) or confirmed complete response (CR) as assessed by BICR and the investigator according to RECIST v1.1 among patients with measurable disease at baseline |
| Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). | BOR was defined as the best response a subject ever achieved after study treatment prior to crossover and any subsequent anticancer therapy, complete response (CR) and partial response (PR) were claimed only if the criteria for each were met at a subsequent time point at least 4 weeks apart. In the case of stable disease (SD), measurements must have met the SD criteria at least once post-baseline no less than 6 weeks from the randomization date. |
| Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin | From the time of randomization to time of death. Note: OS is an event driven endpoint. Subjects who had not died (no record of death) or were lost to follow-up were censored at the date of last known to be alive. | OS by investigator assessment, defined as time from date of randomization until death due to any cause |
| Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator. | From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). | DCR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR), confirmed complete response (CR) or stable disease (SD) or non-CR/non-PD before crossover. |
| Number of Participants With Adverse Events (AEs) | From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm). | Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period |
| Number of Participants With Serious Adverse Events (SAEs) | From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm). | Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period |
| Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator. | From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study). | DOR is defined as the time from initiation of confirmed partial response (PR) or confirmed complete response (CR) to the time of confirmed progressive disease (PD) or death. If subjects do not reach PD or death before crossover, the DOR is censored at the last valid tumor assessment before crossover. |
Countries
Australia, Belgium, Canada, China, France, Germany, Italy, Portugal, Puerto Rico, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
Participants with a diagnosis of advanced/metastatic or inoperable cholangiocarcinoma (CCA) with FGFR2 fusion/rearrangement were recruited to this open-label, randomized, controlled global study across Western Europe, North America, and Asia, based on documented evidence of FGFR2 genetic alteration. The first participant was treated on 18 March 2020. The data cutoff for the analysis was 02 March 2023.
Pre-assignment details
Subjects meeting inclusion/exclusion criteria were randomly assigned 2:1 to receive oral infigratinib 125 mg (N=29) or gemcitabine+cisplatin (N=19). Randomization was stratified by unresectable locally advanced vs metastatic disease, geographic region (North America, Western Europe, Asia Pacific, and rest of the world), prior neoadjuvant/adjuvant treatment (yes/no) and received up to 1 cycle of prior gemcitabine-based chemotherapy for unresectable locally advanced or metastatic disease (yes/no).
Participants by arm
| Arm | Count |
|---|---|
| Infigratinib (BGJ398) 125 mg Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off. | 29 |
| Gemcitabine + Cisplatin Gemcitabine: Gemcitabine 1000 mg/m2 IV D1 and D8 for a 21-day cycle.
Cisplatin: Cisplatin 25 mg/m2 IV D1 and D8 for a 21-day cycle. | 19 |
| Total | 48 |
Baseline characteristics
| Characteristic | Gemcitabine + Cisplatin | Total | Infigratinib (BGJ398) 125 mg |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 14 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 34 Participants | 21 Participants |
| Age, Continuous | 58.2 years STANDARD_DEVIATION 15.25 | 55.8 years STANDARD_DEVIATION 14.04 | 54 years STANDARD_DEVIATION 13.22 |
| BMI | 26.83 kg/m2 STANDARD_DEVIATION 8.019 | 27.79 kg/m2 STANDARD_DEVIATION 7.388 | 28.41 kg/m2 STANDARD_DEVIATION 7.018 |
| ECOG PS 0 | 8 Participants | 27 Participants | 19 Participants |
| ECOG PS 1 | 11 Participants | 21 Participants | 10 Participants |
| ECOG PS 2 | 0 Participants | 0 Participants | 0 Participants |
| FGFR2 Fusion - Central Fusion negative | 0 Participants | 0 Participants | 0 Participants |
| FGFR2 Fusion - Central Fusion positive - fusion partner known | 10 Participants | 25 Participants | 15 Participants |
| FGFR2 Fusion - Central Fusion positive - fusion partner unknown | 0 Participants | 2 Participants | 2 Participants |
| FGFR2 Fusion - Central Fusion positive - intron rearrangement | 0 Participants | 0 Participants | 0 Participants |
| FGFR2 Fusion - Central Missing | 9 Participants | 21 Participants | 12 Participants |
| FGFR2 Fusion - Local Fusion negative | 0 Participants | 0 Participants | 0 Participants |
| FGFR2 Fusion - Local Fusion positive - fusion partner known | 4 Participants | 11 Participants | 7 Participants |
| FGFR2 Fusion - Local Fusion positive - fusion partner unknown | 2 Participants | 2 Participants | 0 Participants |
| FGFR2 Fusion - Local Fusion positive - intron rearrangement | 2 Participants | 4 Participants | 2 Participants |
| FGFR2 Fusion - Local Missing | 11 Participants | 31 Participants | 20 Participants |
| Histological subtype Adenocarcinoma | 19 Participants | 45 Participants | 26 Participants |
| Histological subtype Mixed adeno and squamous | 0 Participants | 0 Participants | 0 Participants |
| Histological subtype Other | 0 Participants | 3 Participants | 3 Participants |
| Initial metastasis (M) diagnosis category M0 | 5 Participants | 13 Participants | 8 Participants |
| Initial metastasis (M) diagnosis category M1 | 14 Participants | 35 Participants | 21 Participants |
| Initial metastasis (M) diagnosis category Missing | 0 Participants | 0 Participants | 0 Participants |
| Initial tumor (T) diagnosis category T0 | 0 Participants | 1 Participants | 1 Participants |
| Initial tumor (T) diagnosis category T1 | 4 Participants | 7 Participants | 3 Participants |
| Initial tumor (T) diagnosis category T2 | 7 Participants | 17 Participants | 10 Participants |
| Initial tumor (T) diagnosis category T3 | 4 Participants | 7 Participants | 3 Participants |
| Initial tumor (T) diagnosis category T4 | 1 Participants | 6 Participants | 5 Participants |
| Initial tumor (T) diagnosis category Tis | 0 Participants | 0 Participants | 0 Participants |
| Initial tumor (T) diagnosis category TX | 3 Participants | 10 Participants | 7 Participants |
| Primary site of cholangiocarcinoma Common bile duct | 1 Participants | 2 Participants | 1 Participants |
| Primary site of cholangiocarcinoma Intrahepatic bile duct | 17 Participants | 45 Participants | 28 Participants |
| Primary site of cholangiocarcinoma Other | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 14 Participants | 34 Participants | 20 Participants |
| Region of Enrollment Europe | 8 participants | 22 participants | 14 participants |
| Region of Enrollment North America | 7 participants | 19 participants | 12 participants |
| Region of Enrollment Southeast Asia | 4 participants | 7 participants | 3 participants |
| Sex: Female, Male Female | 10 Participants | 29 Participants | 19 Participants |
| Sex: Female, Male Male | 9 Participants | 19 Participants | 10 Participants |
| Time from initial diagnosis to randomization | 11.77 months STANDARD_DEVIATION 20.582 | 9.79 months STANDARD_DEVIATION 19.94 | 8.49 months STANDARD_DEVIATION 19.765 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 17 |
| other Total, other adverse events | 29 / 29 | 17 / 17 |
| serious Total, serious adverse events | 10 / 29 | 0 / 17 |
Outcome results
Primary
Progression-free Survival (Central Imaging Assessment)
Defined as the time from randomization until date of disease progression by blinded independent central imaging assessment (Response Evaluation Criteria in Solid Tumors \[RECIST\] v. 1.1) or death, whichever occurs first.
Time frame: From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Progression-free Survival (Central Imaging Assessment) | 7.39 Months |
| Gemcitabine + Cisplatin | Progression-free Survival (Central Imaging Assessment) | 8.02 Months |
Secondary
Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator.
BOR was defined as the best response a subject ever achieved after study treatment prior to crossover and any subsequent anticancer therapy, complete response (CR) and partial response (PR) were claimed only if the criteria for each were met at a subsequent time point at least 4 weeks apart. In the case of stable disease (SD), measurements must have met the SD criteria at least once post-baseline no less than 6 weeks from the randomization date.
Time frame: From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
Population: ITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Infigratinib (BGJ398) 125 mg | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Progressive disease | 2 Participants |
| Infigratinib (BGJ398) 125 mg | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed partial response | 11 Participants |
| Infigratinib (BGJ398) 125 mg | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Not done | 2 Participants |
| Infigratinib (BGJ398) 125 mg | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Stable disease | 14 Participants |
| Infigratinib (BGJ398) 125 mg | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed complete response | 0 Participants |
| Gemcitabine + Cisplatin | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Stable disease | 19 Participants |
| Gemcitabine + Cisplatin | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Progressive disease | 0 Participants |
| Gemcitabine + Cisplatin | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Not done | 1 Participants |
| Gemcitabine + Cisplatin | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed partial response | 9 Participants |
| Gemcitabine + Cisplatin | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed complete response | 0 Participants |
| ORR by Central Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Stable disease | 11 Participants |
| ORR by Central Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed complete response | 0 Participants |
| ORR by Central Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed partial response | 3 Participants |
| ORR by Central Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Progressive disease | 2 Participants |
| ORR by Central Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Not done | 3 Participants |
| ORR by Investigator Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Progressive disease | 3 Participants |
| ORR by Investigator Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed partial response | 2 Participants |
| ORR by Investigator Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Confirmed complete response | 0 Participants |
| ORR by Investigator Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Stable disease | 12 Participants |
| ORR by Investigator Assessment | Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator. | Not done | 2 Participants |
Secondary
Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator.
DCR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR), confirmed complete response (CR) or stable disease (SD) or non-CR/non-PD before crossover.
Time frame: From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator. | 25 Participants |
| Gemcitabine + Cisplatin | Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator. | 28 Participants |
| ORR by Central Assessment | Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator. | 14 Participants |
| ORR by Investigator Assessment | Disease Control Rate (DCR=PR+CR+SD) Determined by Blinded Independent Central Assessment and the Investigator. | 14 Participants |
Secondary
Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator.
DOR is defined as the time from initiation of confirmed partial response (PR) or confirmed complete response (CR) to the time of confirmed progressive disease (PD) or death. If subjects do not reach PD or death before crossover, the DOR is censored at the last valid tumor assessment before crossover.
Time frame: From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
Population: ITT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator. | 5.59 Months |
| Gemcitabine + Cisplatin | Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator. | 7.52 Months |
| ORR by Central Assessment | Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator. | NA Months |
| ORR by Investigator Assessment | Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator. | NA Months |
Secondary
Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin
Defined as the time from randomization until date of disease progression by site investigator (RECIST v1.1) or death, whichever occurs first.
Time frame: From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin | 7.39 Months |
| Gemcitabine + Cisplatin | Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin | 5.19 Months |
Secondary
Number of Participants With Adverse Events (AEs)
Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period
Time frame: From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm).
Population: Safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Number of Participants With Adverse Events (AEs) | 29 Participants |
| Gemcitabine + Cisplatin | Number of Participants With Adverse Events (AEs) | 17 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
Safety analyses were performed for subjects in the safety analysis population for each group. Unless otherwise specified, summaries were provided only for the on-treatment safety assessments, which are the assessments occurring or taken during the on-treatment period
Time frame: From baseline to last dose date of study treatment + 30 days (an average of 7.5 months for the infigratinib arm and 5 months for the gemcitabine + cisplatin arm).
Population: Safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Number of Participants With Serious Adverse Events (SAEs) | 10 Participants |
| Gemcitabine + Cisplatin | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment
ORR is defined as the proportion of subjects with a best overall response (BOR) of either confirmed partial response (PR) or confirmed complete response (CR) as assessed by BICR and the investigator according to RECIST v1.1 among patients with measurable disease at baseline
Time frame: From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).
Population: Intent-to-treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment | 11 Participants |
| Gemcitabine + Cisplatin | Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment | 9 Participants |
| ORR by Central Assessment | Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment | 3 Participants |
| ORR by Investigator Assessment | Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment | 2 Participants |
Secondary
Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin
OS by investigator assessment, defined as time from date of randomization until death due to any cause
Time frame: From the time of randomization to time of death. Note: OS is an event driven endpoint. Subjects who had not died (no record of death) or were lost to follow-up were censored at the date of last known to be alive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Infigratinib (BGJ398) 125 mg | Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin | NA Months |
| Gemcitabine + Cisplatin | Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin | NA Months |