A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations (THOR)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 3

Conditions: Urothelial Cancer

Treatments: Drug: Erdafitinib; Drug: Docetaxel; Drug: Vinflunine; Device: Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA); Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03390504

2017-002932-18 (EudraCT Number)

2023-510296-56-00 (Registry Identifier)

2023-509329-32-00 (Registry Identifier)

CR108401

42756493BLC3001 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-[L]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).

Full description

A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L) 1 agent pembrolizumab, in participants with advanced urothelial cancer and selected FGFR aberrations who have progressed on or after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L) 1 agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2). It will consist of screening, treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment, post-treatment follow-up (from end-of-treatment to participants death, withdraws consent, lost to follow-up study completion for the respective cohort, whichever comes first). The study will have long term extension (LTE) period after clinical cutoff date is achieved for final analysis of each cohort and participants eligible in the opinion of the investigator, will continue to benefit from the study intervention. Efficacy, pharmacokinetics, biomarkers, patient reported outcomes, medical resource utilization and safety will be assessed.

Enrollment: 629 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components ( less than [<] 50 percent [%] overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
• Metastatic or surgically unresectable urothelial cancer
• Documented progression of disease, defined as any progression that requires a change in treatment, prior to randomization
• Cohort 1: Prior treatment with an anti-PD-(L) 1 agent as monotherapy or as combination therapy; no more than 2 prior lines of systemic treatment. Cohort 2: No prior treatment with an anti-PD-(L) 1 agent; only 1 line of prior systemic treatment. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression within 12 months of the last dose are considered to have received systemic therapy in the metastatic setting.
• A woman of childbearing potential who is sexually active must have a negative pregnancy test (beta human chorionic gonadotropin [beta hCG]) at Screening (urine or serum)
• Participants must meet appropriate molecular eligibility criteria
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
• Adequate bone marrow, liver, and renal function

Exclusion criteria

• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to randomization
• Active malignancies (that is, requiring treatment change in the last 24 months). The only allowed exceptions are: urothelial cancer, skin cancer treated within the last 24 months that is considered completely cured, localized prostate cancer with a gleason score of 6 (treated within the last 24 months or untreated and under surveillance) and localized prostate cancer with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence.
• Symptomatic central nervous system metastases
• Received prior fibroblast growth factor receptor (FGFR) inhibitor treatment
• Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients
• Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade.
• History of uncontrolled cardiovascular disease
• Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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629 participants in 4 patient groups

Cohort 1 (Arm 1A): Erdafitinib

Experimental group

Description:

Participants will be screened based on Fibroblast Growth Factor Receptor Inhibitor Clinical Trial Assay (FGFRi CTA) to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-programmed cell death protein PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 milligram (mg), once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustment are based on phosphate level and observed toxicity (adverse events \[AEs\]). Participants who enter in Long-term extension (LTE) phase will continue to receive the erdafitinib tablet as per investigator's decision.

Treatment:

Device: Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

Drug: Erdafitinib

Cohort 1 (Arm 1B): Vinflunine or Docetaxel

Experimental group

Description:

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-PD-\[L\] 1 agent) will receive vinflunine 320 milligram per meter square (mg/m\^2) as a 20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion every 3 weeks. Treatment with either agent (choice of investigator) will be administered until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive Vinflunine or Docetaxel until the participant can commercially receive chemotherapy within the local healthcare system.

Treatment:

Device: Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

Drug: Vinflunine

Drug: Docetaxel

Cohort 2 (Arm 2A): Erdafitinib

Experimental group

Description:

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 mg, once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on phosphate level and observed toxicity (AEs). Participants who enter in LTE phase will continue to receive the erdafitinib tablet as per investigator's decision.

Treatment:

Device: Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

Drug: Erdafitinib

Cohort 2 (Arm 2B): Pembrolizumab

Experimental group

Description:

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive the pembrolizumab until 2 years after the first dose of pembrolizumab (at start of study) or until the participant can commercially receive pembrolizumab within the local healthcare system, whichever comes first.

Treatment:

Device: Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

Drug: Pembrolizumab