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

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib.

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)

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib.

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib.

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects who were confirmed responders (CR or PR) as assessed by BICR (N = 25) or by the Investigator (N = 35).

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib.

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib.

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib.

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects who were confirmed responders (CR or PR) as assessed by BICR (N = 25) or by the Investigator (N = 35).

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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects with both a PFS measure while on infigratinib and available TTP for their last prior line of therapy (N = 103).

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 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.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib Conducted in a subgroup of subjects who were receiving infigratinib as a third or later line of treatment (N=59).

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: 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 (22 June 2022). No formal efficacy analyses were performed for Cohorts 2 and 3.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib Conducted in a subgroup of subjects who were receiving infigratinib as a third or later line of treatment (N = 59).

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 termination of the study, no formal efficacy analyses were performed for Cohorts 2 and 3.

Time frame: 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.

Population: Full Analysis Set (FAS), defined as all subjects in Cohort 1 who had received at least one dose of infigratinib. Conducted in a subgroup of subjects who were receiving infigratinib as a third or later line of treatment (N=59).