A Study of Erdafitinib Compared with Vinflunine or Docetaxel or Pembrolizumab in Subjects with Urothelial Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Mar 2018 → 11 Feb 2026

Decision date (initial)

2024-05-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Research & Development LLC

External identifiers

EU CT number

2023-510296-56-00

EudraCT number

2017-002932-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Safety, Therapy, Pharmacodynamic, Efficacy

The primary objective of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in subjects with advanced urothelial cancer harboring selected 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).
The primary endpoint of overall survival will be evaluated in 2 cohorts:
- Cohort 1: erdafitinib versus chemotherapy (docetaxel or vinflunine) [subjects who have received prior anti-PD(L)1 agent]
- Cohort 2: erdafitinib versus pembrolizumab [subjects who have not received prior anti-PD(L)1 agent]

Conditions and MedDRA coding

Advanced Urothelial Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. ≥18yrs of age (or the legal age of consent in the jurisdiction in which the study is taking place)
2. 2. Histologic demonstration of transitional cell carcinoma of the urothelium. Minor components (<50% overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable.
3. 3. Metastatic or surgically unresectable urothelial cancer
4. 4. Documented PD, defined as any progression that requires a change in treatment, prior to randomization
5. 5.3 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. Prior treatment with an anti-PD-(L)1 agent could have been given as neo-adjuvant, adjuvant, or in metastatic line of treatment as frontline or maintenance therapy, as follows: -Together with chemotherapy or as maintenance therapy -Together with chemotherapy in metastatic setting -For superficial cancer (early disease/non-muscle invasive bladder cancer), OR in neo-adjuvant OR adjuvant setting. If these subjects did not relapse within a year of their last dose of anti-PD-(L)1, this will not be counted as a prior line of systemic treatment. These subjects will however still be eligible only for Cohort 1. Cohort 2: No prior treatment with an anti-PD-(L)1 agent; only 1 line of prior systemic treatment. Note: Subjects who received neoadjuvant or adjuvant chemotherapy or immunotherapy and showed PD within 12m of the last dose are considered to have received systemic therapy in the metastatic setting.
6. 6.1 Subjects must meet appropriate molecular eligibility criteria (as determined by central laboratory screening or by local historical test results (from tissue or blood) performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified or regional equivalent laboratory using the following methods: local nextgeneration sequencing (NGS), direct digital counting methods, or the Qiagen Therascreen FGFR Rotor-Gene Q (RGQ) reverse transcription polymerase chain reaction (RT-PCR) test. Tumors must have at least 1 of the following translocations: FGFR2-BICC1, FGFR2-CASP7, FGFR3-TACC3, FGFR3-BAIAP2L1; or 1 of the following FGFR3 gene mutations: R248C, S249C, G370C, Y373C
7. 7. ECOG performance status Grade 0, 1, or 2
8. 8.4 Adequate bone marrow, liver, and renal function: a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding 2 weeks): Absolute neutrophil count (ANC) >1,500/mm3 Platelet count >75,000/mm3 (≥100,000/mm3 for Cohort 1 subjects at sites choosing vinflunine chemotherapy) Hemoglobin >8.0 g/dL (without transfusion or demonstrate stability, ie; no significant decline in hemoglobin, for 2 weeks after transfusion) b. Liver function: Total bilirubin ≤1.5 x institutional upper limit of normal (ULN) OR direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN [≤1xULN for Cohort 1 subjects at sites choosing docetaxel chemotherapy] Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x institutional ULN or ≤5x institutional ULN for subjects with liver metastases (For subjects in Cohort 1 at sites choosing docetaxel chemotherapy, both the ALT and AST values must be ≤1.5×ULN concomitant with alkaline phosphatase of ≤2.5×ULN) c. Renal function: Creatinine clearance (CrCl) >30 mL/min either directly measured via 24-hour urine collection or calculated using the Cockcroft-Gault formula e. Phosphate:

Exclusion criteria 8

1. For All Subjects 1. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30d prior to randomization
2. 2.2 Active malignancies (ie, requiring treatment change in the last 24m). The only allowed exceptions are: •urothelial cancer •skin cancer treated within the last 24m that is considered completely cured •localized prostate cancer with a Gleason score of 6 (treated within the last 24m or untreated and under surveillance) •localized prostate cancer with a Gleason score of 3+4 that has been treated more than 6m prior to full study screening and considered to have a very low risk of recurrence.
3. 3. Symptomatic central nervous system metastases
4. 4. Received prior FGFR inhibitor treatment
5. 5. Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients
6. 6.2 Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade
7. 7. History of uncontrolled cardiovascular disease including: a. unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac arrest, or known congestive heart failure Class III-V (Attachment 3) within the preceding 3 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months. b. QTc prolongation as confirmed by triplicate assessment at screening (Fridericia; QTc >480 milliseconds). c. Pulmonary embolism or other venous thromboembolism (VTE) within the preceding 2 months
8. 9.1 Known active hepatitis B or C infection PCR-negative on all available tests for the past 6 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is overall survival (OS). Overall survival is measured from the date of randomization to the date of the subject's death. If the subject is alive or the vital status is unknown, the subject will be censored at the date the subject was last known to be alive

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen Cilag International

Sponsor organisation

Janssen Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen Cilag International

Contact name

CTIS Point of Contact

Third parties 1

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications