A Phase Ib-II Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer
Study Identifier:
42756493BLC2002
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Study Complete
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Study Summary
To identify the recommended Phase 2 dose (RP2D) and schedule of erdafitinib in combination with cetrelimab (Phase 1b)
To evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in first line metastatic urothelial carcinoma (mUC) setting (Phase 2).
To evaluate the objective response rate of the selected dose regimen out of 2 possible dose regimens of JNJ42756493 in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
To evaluate the efficacy and safety of 2 different dose regimens of JNJ42756493 in participants with urothelial cancer.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Study Complete
Requirements information
Inclusion criteria
- 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
- Metastatic or locally advanced urothelial cancer
- Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
- Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (?) 60 mL/min as calculated by Cockcroft-Gault; 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
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2
- PER SPAIN registry
- 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 women of childbearing potential: agree to use a condom with spermicidal foam/gel/film/cream/suppository during the study and for 5 months 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 or sperm, respectively, during the study and for 5 months after the last dose of study drug.
- Examples of highly effective methods include:
- user-independent methods: implantable progestogen-only hormone contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormonereleasing system; vasectomized partner;
- user-dependent methods: combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, and transdermal; progestogen-only hormone contraception associated with inhibition of ovulation: oral and injectable.
- - Sexual abstinence
- 10.Women of childbearing potential must have a negative pregnancy test at screening within < =7 days of C1D1 (first dose of study drug) using a highly sensitive pregnancy test (serum beta-human chorionic gonadotropin [beta-hCG]
- 11.Sign an informed consent form indicating that he or she understands the purpose of and procedures required for the study, and is willing and able to participate in the study.
- 12.Willing and able to adhere to the prohibitions and restrictions.
Exclusion criteria
- Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks
- Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; 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
- Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)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
- Active malignancies requiring concurrent therapy other than urothelial cancer
- Symptomatic central nervous system metastases
- Per Spain Registry
- 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 3m
- 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
- 13.1Phase 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 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.Criterion modified Amend.2
- 15.1Allergies, 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.Criterion modified Amend.2
- 16.1Current central serous retinopathy (CSR) or retinal pigment
- epithelial detachment (RPED) of any Grade.
- 17.Criterion deleted Amend. 2
- 18. Criterion modified Amend.2
- 18.1 Use of immunosuppressant agents, including, but not limited to: 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 within 28 days 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. Criterion modified Amend. 3
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Victor Moreno Garcia
Status
Recruitment Complete
Condition(s) Treated at Site
Urinary tract