A study to evaluate the safety, the distribution and elimination of the compound in the body, and the effectiveness of Erdafitinib by itself, in combination with JNJ-63723283 (Cetrelimab) or in combination with JNJ- 63723283 (Cetrelimab) and chemotherapy, in patients with metastatic or Locally Advanced urothelial cancer.

Phase 1

Conditions: Metastatic or Locally Advanced Urothelial Cancer
MedDRA version: 20.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-001980-19-BE

Lead Sponsor: Janssen-Cilag International NV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 160

Inclusion Criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. =18 years of age.
2. Criterion modified per Amendment 2
2.1 Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable.
3. Criterion modified per Amendment 2
3.1 Metastatic or locally advanced urothelial cancer (Stage IV disease per AJCC Staging Guidelines)
4. Criterion modified per Amendment 2
4.1 Criterion modified per Amendment 3
4.2 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Meet appropriate molecular eligibility criteria. Tumors must have at least one gene fusion or gene mutation.
5. Criterion modified per Amendment 2
5.1 Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline.
6. Criterion modified per Amendment 2
6.1 Criterion modified per Amendment 3
6.2 Prior systemic therapy for metastatic urothelial cancer: Phase 1b erdafitinib + cetrelimab cohort:
–Any number of lines of prior therapy
–Renal function for subjects must have a creatinine clearance (CrCl) =30 mL/min as calculated by Cockcroft-Gault
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort:
–No prior systemic therapy for metastatic disease. Note: Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression, within 12 months of the last dose are considered to have received systemic chemotherapy in the metastatic setting
–Renal function for subjects must have a CrCl =30 mL/min to receive carboplatin and =60 mL/min to receive cisplatin as calculated by Cockcroft-Gault.
Phase 2:
–No prior systemic therapy for metastatic disease. Note: Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease progression, within 12 months of the last dose are considered to have received systemic chemotherapy in the metastatic setting.
–Cisplatin-ineligible based on:
o ECOG PS 0-1 AND at least one of the following criteria:
–Renal function defined as CrCl =60 mL/min as calculated by Cockcroft- Gault (Galsky 2011)
–Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0.
–Grade 2 or higher hearing loss per NCI-CTCAE version 5.0, OR
–ECOG PS 2.
7. Criterion modified per Amendment 2
7.1 Criterion modified per Amendment 3
7.2 ECOG PS Grade as defined below:
Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and ECOG 0-2 for carboplatin.
Phase 2: ECOG 0-2
8. Criterion modified per Amendment 1
8.1 Criterion modified per Amendment 2
8.2 Criterion modified per Amendment 3
8.3 Adequate organ function at Screening
9. Criterion modified per Amendment 2
9.1 Criterion modified per Amendment 1
9.2 Criterion modified per Amendment 3
9.3 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Before the first dose of study drug:
Women of childbearing potential (defined as: fertile, following menarche and until becoming post-menopausal unless permanently sterile as a result of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) and fertile men who are sexually active must agree to use a highly effective method of contraception during the study and for 5 months after the last dose of study drug. For men who are sexually active with wome

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study:
1. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to C1D1. For Phase 1b, subjects who have received the following prior anti- tumor therapy:
– Received nitrosoureas and mitomycin C within 6 weeks.
2. Criterion modified per Amendment 3
2.1 Phase 1b erdafitinib + cetrelimab cohort:
–Chemotherapy within 3 weeks of C1D1.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2:
–Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation.
3. Criterion modified per Amendment 2
3.1 Criterion modified per Amendment 3
3.2 Prior anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed.
4. Criterion modified per Amendment 2
4.1 Active malignancies requiring concurrent therapy other than urothelial cancer.
5. Symptomatic central nervous system metastases.
6. Prior FGFR inhibitor treatment.
7. Radiation therapy =30 days prior to planned C1D1.
8. Criterion modified per Amendment 2
8.1 Criterion modified per Amendment 3
8.2 History of uncontrolled cardiovascular disease including:
– Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac arrest, or known congestive heart failure Class III-V within the preceding 3 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months.
9. Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome.
10. Any of the following:
– Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection.
– Active autoimmune disease or a documented history of autoimmune disease that requires systemic steroids or immunosuppressive agents.
– Grade 3 or higher toxicity effects from previous treatment with immunotherapy.
– Psychiatric conditions (eg, alcohol or drug abuse), dementia, or altered mental status.
– Any other issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments.
11. Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation.
12. Active or chronic hepatitis B or hepatitis C disease as determined by hepatitis B surface antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody (anti-HCV) positivity at Screening. If positive, further testing of quantitative levels to rule out active infection is required.
13. Criterion modified per Amendment 3
13.1 Phase 1b erdafitinib + cetrelimab and Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are considered by the investigator as not clinically significant).
Phase 2: Not recov

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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