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.
- Conditions
- Metastatic or locally advanced Urothelial CancerMedDRA 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-IT
- 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
- 115
1.>=18 years of age
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.Metastatic or locally advanced urothelial cancer (Stage IV disease per AJCC Staging Guidelines)
4. Meet appropriate molecular eligibility criteria. Tumors must have at least one gene fusion or gene mutation.
5.Must have measurable disease by radiological imaging according to the response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline..
6.Prior systemic therapy:
Phase1b + any 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 >50 mL/min as calculated by Cockcroft-Gault.
Phase2: Progressed after 1 or 2 lines of prior chemotherapy
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:
– 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. 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.Adequate organ function at screening Please refer to protocol
9.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 first dose of study drug:contraception (<1%/year failure rate) during the study and for5months after the last dose of study drug. For men who are sexually active with women of childbearing potential: agree to use a condom with spermicidal foam/gel/film/cream/suppository during the study and for5months after the last dose of study drug. Contraception must be consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, during the study and for5months after the last dose of study drug.
10.Women of childbearing potential must have a negative pregnancy test at screening within =7days of C1D1 (first dose of study drug) using a highly sensitive pregnancy test
11.Sign Molecular and Full-Study ICF indicating tha
1.Treatment with any other investigational agent or participation in other clinical study with therapeutic intent within 30days prior toC1D1.For Ph1b, pt who have received the following prior antitumor therapy:- Received nitrosoureas and mitomycin C within6weeks
2.Chemotherapy within3weeks ofC1D1
3.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
4.Active malignancies requiring concurrent therapy other than urothelial cancer
5.Symptomatic CNS metastases
6.Prior FGFR inhibitor treatment
7.RT=30days prior to plannedC1D1
8.History of uncontrolled cardiovascular disease including:a.Unstable angina, myocardial infarction, ventricular fibrillation,Torsades de Pointes, cardiac arrest, or known congestive heart failure ClassIII-Vwithin the preceding3months;cerebrovascular accident or transient ischemic attack within the preceding3months.b.Corrected QTc interval prolongation as confirmed by triplicate assessment at screening(QTcF>480ms).c.Pulmonary embolism or other venous thromboembolism within the preceding2months
9.Known to be seropositive for HIV or AIDS
10.-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-Grade3or higher toxicity effects from previous treatment with immunotherapy-Psychiatric conditions, dementia, or altered mental status.-Any other issue that would impair the ability of the subject to partecipate to the study
11.Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation
12.Active or HBV or HCV disease
13.Not recovered from reversible toxicity of prior anticancer therapy Phase 2: Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are considered by the investigator as not clinically significant such as alopecia, or skin discoloration).
14.Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions
15.Allergies, hypersensitivity, or intolerance to protein-based therapies or with a history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or immune-mediated thrombocytopenia or anemia), or to excipients of erdafitinib or cetrelimab
16.Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade
17.Use of oral or parenteral CYP3A4 inhibitor
18 Use of immunosuppressant agents, including, but not limited to: systemic corticosteroids at doses exceeding 10 mg/day of prednisone or its equivalent, methotrexate, cyclosporine, azathioprine, and tumor necrosis factor a (TNF-a)blockers, within 2 weeks before the planned first dose of study drug.
19.Vaccinated with a live attenuated vaccine within28days prior to the first dose of study drug and for 3 months after receiving the last dose of study drug. Annual inactivated influenza vaccine is permitted
20.Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 5 months after receiving the last dose of study drug
21.Plans to father a child while enrolled in this study or within 5months after receiving the last dose of study drug
22.Major surgery within 4 weeks of enro
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