Neoplasms

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Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Carboplatin

Pembrolizumab

Cisplatin

Mitogens

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Combination of pemigatinib (13.5 milligrams \[mg\] once a day orally) plus pembrolizumab (200 mg every 3 weeks \[Q3W\] intravenously \[IV\])

Pemigatinib (13.5 mg once a day orally) alone

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.

Pemigatinib

1000 mg/m\^2 IV over 30 minutes on Days 1 and 8 of each 3-week cycle

Dosed to target AUC of 5 mg/mL/min or 4.5 mg/mL/min if required per local guidelines on Day 1 or 2 of each 3-week cycle

Luis Feliz Vinas, MD

The purpose of this study is to evaluate the safety and efficacy of pemigatinib plus pembrolizumab or pemigatinib alone versus the standard of care for participants with metastatic or unresectable urothelial carcinoma who are not eligible to receive cisplatin, are harboring FGFR3 mutation or rearrangement, and who have not received prior treatment.

Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)

A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Plus Pembrolizumab Versus Pemigatinib Alone Versus Standard of Care as First-Line Treatment for Metastatic or Unresectable Urothelial Carcinoma in Cisplatin-Ineligible Participants Whose Tumors Express FGFR3 Mutation or Rearrangement (FIGHT-205)

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

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.

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

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).

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).

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.

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.

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. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

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.

Incyte Corporation

TEAEs, defined as adverse events that were either reported for the first time or the worsening of pre-existing events after the first dose of study drug until 30 days after the last dose of study drug, are reported for members of the Safety Population (all randomized participants who received at least one dose of study treatment).

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).

Pemigatinib 13.5 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.

Pemigatinib 13.5 mg Plus 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.

Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg

Total

57 to 84 years old

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

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

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.

Study Director

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.

Progression-free Survival (PFS)

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

Overall Survival (OS)

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.

Objective Response Rate (ORR)

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

Duration of Response (DOR)

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.

Spots Global Cancer Trial Database for fgfr3 mutation