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

Lead sponsor

Janssen Research & Development, LLC is the lead sponsor of 932 studies on the registry; 76 are open to participants now.

Of its 285 completed or terminated interventional studies of FDA-regulated products, 137 (48%) have results posted.

Study arms

• Experimental
  Cohort 1 (Arm 1A): Erdafitinib

  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.

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

• Experimental
  Cohort 1 (Arm 1B): Vinflunine or Docetaxel

  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.

  Drug: Vinflunine · Drug: Docetaxel · Device: Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

• Experimental
  Cohort 2 (Arm 2A): Erdafitinib

  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.

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

• Experimental
  Cohort 2 (Arm 2B): Pembrolizumab

  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.

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

Interventions

• DrugErdafitinib

  Participants will swallow erdafitinib tablets orally at a starting dose of 8 mg.

  Also known as: JNJ-42756493

• DrugVinflunine

  Participants will receive vinflunine 320 mg/m\^2 as a 20-minute intravenous infusion.

• DrugDocetaxel

  Participants will receive docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion.

• DrugPembrolizumab

  Participants will receive pembrolizumab 200 mg as a 30-minute intravenous infusion.

• DeviceFibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

  FGFRi CTA will be used to determine molecular eligibility.

Primary outcomes

1. Overall Survival (OS)

   Overall survival was measured from the date of randomization to the date of the participant's death.

   Time frame: From randomization (3 days prior to Cycle 1 Day 1) until death due to any cause (maximum up to 51.7 months)

Secondary outcomes

1. Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1

   PFS was defined as the time from the date of randomization to the date of disease progression or relapse from complete response (CR) based on investigator assessment using RECIST v 1.1, or death due to any cause, whichever occurred first. As per RECIST v 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (\<) 10 millimeters (mm). Progressive disease (PD) was defined as at least 20 percent (%) increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of greater than or equal to (\>=) 5 mm or appearance of at least 1 new lesion.

   Time frame: From randomization (3 days prior to Cycle 1 Day 1) until disease progression or relapse from CR or death (maximum up to 51.7 months)

2. Objective Response Rate (ORR) Per RECIST Version 1.1

   ORR was defined as the percentage of participants who achieved CR or partial response (PR) as determined by investigator per RECIST v1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

   Time frame: From start of the treatment (Day 1 Cycle 1) up to maximum of 51.7 months

3. Change From Baseline in Physical Functioning Scales of the Functional Assessment of Cancer Therapy - Bladder Cancer (FACT-Bl)

   The FACT-Bl consisted of 39 items, with 5-point Likert scales, covering 5 primary domains: physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns for participants with bladder cancer. The response options ranged from 0 to 4 where, 0='Not at all" and 4= "very much." FACT-Bl total score ranged from 0 (worst) to 156 (best). The higher the score, the better the quality of life (QOL). The baseline value was defined as the value collected at the time closest to but prior to the randomization.

   Time frame: Baseline up to Cycle 11 (each cycle was of 21 days)

4. Time Until Symptom Deterioration

   Time until symptom deterioration was defined as the first time to increase in urinary bladder cancer symptoms score from the day of randomization beyond a meaningful change threshold compared to baseline. The urinary bladder cancer symptom score was subset of FACT-Bl which included 3 items related to urinary symptoms, 5-point Likert scale. Response options ranged from 0 to 4, 0 = Not at all, 1= A little bit, 2= Somewhat, 3=Quite a bit, 4 = Very much. A response of 0 indicated no symptoms and 4 indicated severe symptoms. Total sum scores ranged from 0 to 12, higher scores indicate relatively poor quality of life.

   Time frame: Randomization (3 days prior to Cycle 1 Day 1) up to maximum of 51.7 months

5. Percentage of Participants With Shift From Baseline in Patient-Global Impression of Severity (PGIS)

   The PGI-S was a single item patient-reported measure assessing participants' impression of severity in bladder cancer symptoms. It uses a 4-point Likert scale as follows: symptoms are: 0-"absent (no symptoms)", 1-"mild", 2-"moderate", 3="severe" and 4= "very severe". Percentage of participants with shift from baseline in PGIS score were reported. A negative shift from baseline in PGIS score indicated Improvement and positive shift from baseline in PGIS score indicated Worsening. The baseline value was defined as the value collected at the time closest to but prior to the randomization.

   Time frame: Baseline, 51.7 months

6. Change From Baseline in Utility Scale of the European Quality of Life-5 Dimensions-5 Levels Questionnaire (EQ-5D-5L)

   The EQ-5D-5L was a generic measure of health status. The EQ-5D-5L was a 5-item questionnaire that assessed 5 domains included mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Health utility values generated from the EQ-5D generally range from 0 (a state as bad as being dead) to 1 (full health), with higher scores indicating better QoL. The EQ visual analog scale (VAS) recorded the patient's self-rated health on a VAS, ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating better QoL. The baseline value was defined as the value collected at the time closest to but prior to the randomization.

   Time frame: Baseline up to Cycle 11 (each cycle was of 21 days)

7. Change From Baseline in Visual Analog Scale (VAS) of the European Quality of Life-5 Dimensions-5 Levels Questionnaire (EQ-5D-5L)

   The EQ-5D-5L was a generic measure of health status. The EQ-5D-5L was a 5-item questionnaire that assessed 5 domains included mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Health utility values generated from the EQ-5D generally range from 0 (a state as bad as being dead) to 1 (full health), with higher scores indicating better QoL. The EQ VAS recorded the patient's self-rated health on a VAS, ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating better QoL. The baseline value was defined as the value collected at the time closest to but prior to the randomization.

   Time frame: Baseline up to Cycle 11 (each cycle was of 21 days)

8. Duration of Response (DOR) as Per RECIST Version 1.1

   DOR was defined as time from the date of initial documentation of an overall response (CR or PR) to the date of first documented evidence of progressive disease (PD) (or relapse for participants who experience CR) or death. As per RECIST Version 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion.

   Time frame: From date of first documented response to date of first documented PD or death whichever occurred first (maximum up to 51.7 months)

9. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

   An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. All TEAEs including serious and non-serious events were reported in this outcome measure.

   Time frame: From start of the treatment (Day 1 Cycle 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy (maximum up to 51.7 months)

10. Number of Participants With Shift From Baseline Grade Less Than or Equal to (<=) 2 to Grade Greater Than or Equal to (>=) 3 Post-Baseline in Laboratory Parameter: Hematology

    Hematology parameters included: hemoglobin, platelet count, white blood cell (WBC) count, and absolute neutrophil count (ANC). According to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE and Grade 0= normal. In this outcome measure number of participants with shifts from baseline (BL) Grade \<= 2 to Grade \>=3 post-baseline in any of hematology parameters are reported. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only those categories in which at least one participant had data were reported in this outcome measure.

    Time frame: From baseline up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (maximum up to 51.7 months)

11. Number of Participants With Shift From Baseline Grade <= 2 to Grade >=3 Post-Baseline in Laboratory Parameter: Chemistry

    Chemistry parameters included: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, bicarbonate, corrected calcium, magnesium, potassium, sodium, serum phosphate, serum parathyroid hormone. According to NCI-CTCAE version 4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE and Grade 0= normal. In this outcome measure number of participants with shifts from baseline (BL) Grade \<= 2 to Grade \>=3 post-baseline in any of chemistry parameters are reported. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only those categories in which at least one participant had data were reported in this outcome measure.

    Time frame: From baseline up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (maximum up to 51.7 months)

12. Number of Participants With Abnormalities in Electrocardiograms (ECG) Parameters

    Number of participants with abnormalities in ECG parameters were reported. The ECG variables included heart rate, RR interval, PR interval, QRS interval, QT interval and QT corrected according to Fridericia's formula (QTcF). ECG abnormality criteria include: Heart rate: Low \<50 beats per minute (bpm); High \> 100 bpm, RR interval: Low \< 600 milliseconds (ms); High \> 1000 ms, QT interval: High \> 500 ms, QTc interval: High \> (450 ms for males, 470 ms for females); increase to \>500 ms.

    Time frame: Day 1 of Cycle 2 and 4 (Each Cycle 21 days)

13. Change From Baseline in Vital Signs: Weight

    Changes from baseline in vital signs (weight) was reported. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug.

    Time frame: Baseline, 51.7 months

14. Number of Participants With Shift From Baseline to Worst Post-baseline Ophthalmologic Examination: Amsler Grid Test

    Number of participants with shift from baseline to worst post-baseline in Amsler grid test was reported. Baseline and post-baseline visit findings included normal, abnormal CS (clinically significant) and abnormal NCS (not clinically significant). Clinical significance was determined by investigator's assessment. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening post-baseline measurement was reported.

    Time frame: From baseline up to maximum of 51.7 months

15. Number of Participants With Shift From Baseline to Worst Post-baseline Ophthalmologic Examination: Visual Acuity

    Number of participants with shift from baseline to worst post-baseline in visual acuity (VA) was reported. Worst post-baseline was defined as the visual acuity value that resulted in the largest change from baseline value for either eye. Baseline value was considered for the eye that reported the worst-post baseline value. Baseline and post-baseline visit visual acuity findings included: \<= 20/30, \>20/30 to \<= 20/40, \>20/40 to \<= 20/80, \>20/80 to \<= 20/120, \>20/120 to \<= 20/160, \>20/160 to \<= 20/200, \>20/200. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening in visual acuity from baseline value to worst post-baseline measurement was reported.

    Time frame: From baseline up to maximum of 51.7 months

16. Number of Participants With Shift From Baseline to Worst Post-baseline Ophthalmologic Examination: Optical Coherence Tomography: Subretinal Fluid

    Number of participants with shift from baseline to worst post-baseline in optical coherence tomography for subretinal fluid was reported. At the baseline visit, findings may have been absent or present/visible. At all post-baseline visits, findings were compared to baseline and results may have been increased, decreased, stable or resolved. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only category (shift from absent at baseline to increased at post-baseline) in which at least one participant had data for worsening post-baseline measurement was reported.

    Time frame: From baseline up to maximum of 51.7 months

17. Number of Participants With Shift From Baseline to Worst Post-baseline Ophthalmologic Examination: Optical Coherence Tomography: Retinal Pigment Epithelium (RPE) Elevation

    Number of participants with shift from baseline to worst post-baseline in optical coherence tomography for RPE elevation was reported. At the baseline visit, findings may have been absent or present/visible. At all post-baseline visits, findings were compared to baseline and results may have been increased, decreased, stable or resolved. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening post-baseline measurement was reported.

    Time frame: From baseline up to maximum of 51.7 months

18. Number of Participants With Shift From Baseline to Worst Post-baseline Ophthalmologic Examination: Slit Lamp Biomicroscopy: Retinal Assessment

    Number of participants with shift from baseline to worst post-baseline in slit lamp biomicroscopy examination for retinal assessment was reported. Baseline and post-baseline visit findings included normal, abnormal CS and abnormal NCS. Clinical significance was determined by investigator's assessment. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening post-baseline measurement was reported.

    Time frame: From baseline up to maximum of 51.7 months

19. Oral Clearance (CL/F) of Erdafitinib

    Clearance was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

    Time frame: Day 14 of Cycle 1, Day 1 of Cycle 2: pre-dose and 2-4 hours post-dose (each cycle was of 21 days)

20. Area Under the Plasma Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of Erdafitinib

    Area under the plasma concentration time-curve from time zero to the time t (AUC\[0-t\]) was reported.

    Time frame: Day 14 of Cycle 1, Day 1 of Cycle 2: pre-dose and 2-4 hours post-dose (each cycle is of 21 days)

Baseline characteristics

Publications

• Kato M, Yoshida M, Horio H, Furukawa Y, Ote T, Ohe C. Sample-Related Factors Associated With FGFR Testing Validity in Urothelial Cancer: A Japanese THOR Post Hoc Analysis. Cancer Sci. 2026 Nov 9:10.1111/cas.70588. doi: 10.1111/cas.70588. Online ahead of print. PubMed 43004726 ↗
• Nakagawa R, Hori T, Kamijima T, Kadomoto S, Makino T, Naito R, Iwamoto H, Yaegashi H, Shigehara K, Nohara T, Izumi K, Mizokami A. Response-durability phenotypes and clinical benefit with erdafitinib: a THOR trial post hoc analysis. BJU Int. 2026 Nov 9. doi: 10.1111/bju.70533. Online ahead of print. PubMed 43001410 ↗
• Loriot Y, Matsubara N, Park SH, Huddart RA, Burgess EF, Houede N, Banek S, Guadalupi V, Ku JH, Valderrama BP, Tran B, Triantos S, Kean Y, Akapame S, Deprince K, Mukhopadhyay S, Stone NL, Siefker-Radtke AO; THOR Cohort 1 Investigators. Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2023 Nov 23;389(21):1961-1971. doi: 10.1056/NEJMoa2308849. Epub 2023 Oct 21. PubMed 37870920 ↗

Study documents

• Study protocol ↗ · Jan 20, 2023
• Statistical analysis plan ↗ · Jan 24, 2023

PDFs hosted by the registry, ClinicalTrials.gov.