Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Stand... | NCT04003610

NCT04003610

ID	Type	Description	Link
2019-000721-50	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pemigatinib + Pembrolizumab	Experimental	Combination of pemigatinib (13.5 milligrams [mg] once a day orally) plus pembrolizumab (200 mg every 3 weeks [Q3W] intravenously [IV])	Drug: Pemigatinib Drug: Pembrolizumab
Pemigatinib	Experimental	Pemigatinib (13.5 mg once a day orally) alone	Drug: Pemigatinib
Standard of Care	Active Comparator	Either gemcitabine plus carboplatin or pembrolizumab as standard of care. Gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or 2 of each 3-week cycle. Pembrolizumab 200 mg IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.	Drug: Gemcitabine Drug: Carboplatin

Name	Type	Description	Arm Group Labels	Other Names
Pemigatinib	Drug	13.5 mg once a day orally	Pemigatinib Pemigatinib + Pembrolizumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from the randomization date until the date of disease progression (as measured by a blinded independent central review [BICR] per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) or death due to any cause, whichever occurred first.	up to 130 days

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from the date of randomization until death due to any cause.	up to 225 days
Objective Response Rate (ORR)	ORR was defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 (as measured by BICR).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically documented metastatic or unresectable urothelial carcinoma. Both transitional cell and mixed transitional cell histologies are allowed, provided urothelial component is ≥ 50%.
At least 1 measurable target lesion per RECIST v1.1.
Must be ineligible to receive cisplatin. Patients ineligible for any platinum-based chemotherapy are allowed.
Known FGFR3 mutation or rearrangement confirmed by the central laboratory prior to randomization.
Central laboratory test result of PD-L1 status is mandatory at screening.
Have received no prior systemic chemotherapy for metastatic or unresectable urothelial carcinoma (except adjuvant platinum-based chemotherapy following radical cystectomy, with recurrence > 12 months from completion of therapy, or neo-adjuvant platinum-based chemotherapy, with recurrence > 12 months since completion of therapy).
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

Prior receipt of a selective FGFR inhibitor for any indication or reason.
Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor.
Receipt of anticancer medications or investigational drugs for unresectable and/or metastatic disease.
Concurrent anticancer therapy, except for treatment allowed per protocol.
Has disease that is suitable for local therapy administered with curative intent.
Has tumor with any neuroendocrine or small cell component.
Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment.
Has central nervous system metastases, unless the participant has completed local therapy (eg, whole brain radiation therapy, surgery, radiosurgery) and has discontinued use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study.
Known additional malignancy that is progressing or required active treatment within the past 3 years
Laboratory values outside the protocol-defined range at screening.
Clinically significant or uncontrolled cardiac disease.
History of autoimmune disease that has required systemic treatment in past 2 years.

Contacts/Locations Module

Name	Affiliation	Role
Luis Feliz Vinas, MD	Incyte Corporation	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Marin Cancer Care		Greenbrae	California	94904	United States
Christiana Care Helen F. Graham Cancer Center

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 17, 2020	Mar 17, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

No participants were enrolled in the pemigatinib 13.5 mg treatment arm.

Arm/Group Information

ID	Title	Description
BG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
BG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.
BG002	Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg	Participants received either gemcitabine plus carboplatin or pembrolizumab as standard of care. Participants received gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8 of each 3-week treatment cycle, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or Day 2 of each 3-week treatment cycle. Treatment continued for 4 to 6 cycles (or per institutional standards) until disease progression or intolerable toxicity. Pembrolizumab 200 mg was administered IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

57 to 84 years old

Title	Measurements
	BG0000 BG0011 BG0026 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG001NADue to low participant enrollment in this arm, data are not being reported, as doing so may risk participant identification. BG0024 BG003

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG001NADue to low participant enrollment in this arm, data are not being reported, as doing so may risk participant identification. BG0020 BG003

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG001NADue to low participant enrollment in this arm, data are not being reported, as doing so may risk participant identification. BG0020 BG003

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS)

PFS was defined as the time from the randomization date until the date of disease progression (as measured by a blinded independent central review [BICR] per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) or death due to any cause, whichever occurred first.

Intent-to-Treat (ITT) Population: all participants who were randomized into the study. Treatment groups for this population were to be determined according to the treatment assignment at the time of randomization. The 95% confidence intervals were calculated using the Brookmeyer and Crowley's method.

Posted

Median

95% Confidence Interval

months

up to 130 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.
OG002	Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg	Participants received either gemcitabine plus carboplatin or pembrolizumab as standard of care. Participants received gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8 of each 3-week treatment cycle, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or Day 2 of each 3-week treatment cycle. Treatment continued for 4 to 6 cycles (or per institutional standards) until disease progression or intolerable toxicity. Pembrolizumab 200 mg was administered IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Units	Counts
Participants	OG0000 OG0011 OG0026

Title

Denominators

Categories

Title	Measurements
	OG0011.81(NA to NA)The upper and lower limits of the confidence interval were not estimable because too few participants had disease progression or died. OG0022.12(1.51 to NA)The upper limit of the confidence interval was not estimable because too few participants had disease progression or died.

Secondary

Overall Survival (OS)

OS was defined as the time from the date of randomization until death due to any cause.

ITT Population. The 95% confidence intervals were calculated using the Brookmeyer and Crowley's method.

Posted

Median

95% Confidence Interval

months

up to 225 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Secondary

Objective Response Rate (ORR)

ORR was defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 (as measured by BICR).

Posted

Number

percentage of participants

up to 148 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Secondary

Duration of Response (DOR)

DOR was defined as the time from the date of the first assessment of CR or PR until the date of the first disease progression (per RECIST v1.1) or death, whichever occurred first (as measured by BICR).

As measured by BICR, there were no responders; thus, DOR was not calculated.

Posted

up to 148 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Secondary

Number of Participants With Treatment-emergent Adverse Events

A treatment-emergent adverse event was defined as an adverse event that was either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug.

Safety Population: all randomized participants who received at least one dose of study treatment. Treatment groups for this population were to be determined according to the actual treatment the participant received regardless of assigned study drug treatment.

Posted

Count of Participants

Participants

up to 178 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Secondary

EORTC QLQ-C30 Score

The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.

ITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

scores on a scale

up to 160 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Secondary

Change From Baseline in the EORTC QLQ-C30 Score

ITT Population. Only participants with available data were analyzed.

Posted

Mean

Standard Deviation

scores on a scale

Baseline; up to 160 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg

Secondary

Number of Participants With the Indicated EQ-5D-5L Dimension Scores

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.

ITT Population. Only participants with available data were analyzed

Posted

Count of Participants

Participants

up to 160 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Secondary

Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score

ITT Population. Only participants with available data were analyzed

Posted

Mean

Standard Deviation

scores on a scale

Baseline; up to 160 days

ID	Title	Description
OG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).
OG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pemigatinib 13.5 mg	Pemigatinib was self-administered at 13.5 milligrams (mg) once daily (QD) orally (PO) until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/deciliter [dL]) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related adverse event (AE).	0	0	0	0	0	0
EG001	Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg	Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.	0	1	1	1	1	1
EG002	Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg	Participants received either gemcitabine plus carboplatin or pembrolizumab as standard of care. Participants received gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8 of each 3-week treatment cycle, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or Day 2 of each 3-week treatment cycle. Treatment continued for 4 to 6 cycles (or per institutional standards) until disease progression or intolerable toxicity. Pembrolizumab 200 mg was administered IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.	3	6	1	6	6	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment		EG0000 at risk EG0011 events1 affected1 at risk EG0020 events0 affected6 at risk
COVID-19	Infections and infestations	MedDRA 24	Systematic Assessment		EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0022 events1 affected6 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24	Systematic Assessment	EG0000 at risk EG0011 events1 affected1 at risk EG0021 events1 affected6 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24	Systematic Assessment	EG0000 at risk EG0011 events1 affected1 at risk EG0020 events0 affected6 at risk
Asthenia	General disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0022 events2 affected6 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0022 events2 affected6 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Cellulitis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Cheilitis	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Constipation	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0023 events3 affected6 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Delirium	Psychiatric disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0011 events1 affected1 at risk EG0020 events0 affected6 at risk
Escherichia bacteraemia	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0011 events1 affected1 at risk EG0020 events0 affected6 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0011 events1 affected1 at risk EG0020 events0 affected6 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Hypofibrinogenaemia	Blood and lymphatic system disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Malaise	General disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0022 events2 affected6 at risk
Nausea	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0022 events2 affected6 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Oedema peripheral	General disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Penile pain	Reproductive system and breast disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Platelet count decreased	Investigations	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Pyelonephritis	Infections and infestations	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0011 events1 affected1 at risk EG0020 events0 affected6 at risk
Vascular pain	Vascular disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24	Systematic Assessment	EG0000 at risk EG0010 events0 affected1 at risk EG0021 events1 affected6 at risk

The Sponsor made a decision unrelated to safety to halt study enrollment. Due to early termination of the study with only 7 participants, no analysis of efficacy endpoints was done.

Certain Agreements

First MCP Posted Date

ID	Term
D002295	Carcinoma, Transitional Cell
D000168	Acrocephalosyndactylia
D009362	Neoplasm Metastasis

Ancestor Terms

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D003398	Craniosynostoses
D013580	Synostosis
D004413	Dysostoses
D001848	Bone Diseases, Developmental
D001847	Bone Diseases
D009140	Musculoskeletal Diseases
D013576	Syndactyly
D019465	Craniofacial Abnormalities
D009139	Musculoskeletal Abnormalities
D017880	Limb Deformities, Congenital
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000705477	pemigatinib
C582435	pembrolizumab
D000093542	Gemcitabine
D016190	Carboplatin

Ancestor Terms

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D056831	Coordination Complexes
D009930	Organic Chemicals

Total not calculated because data are not available (NA) in one or more arms.

Pemigatinib was self-administered at 13.5 mg QD PO until disease progression during each 21-day treatment cycle. Participants not reaching the target serum phosphate level (> 5.5 mg/dL) during Cycle 1 despite being study drug compliant increased the daily pemigatinib dose to 18 mg starting at Cycle 2 as long as they were not experiencing an ongoing Grade 2 or higher treatment-related AE. Pembrolizumab 200 mg was administered intravenously (IV) on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.

A standard deviation was not calculated when only 1 participant contributed to the analysis.