Metastatic or Surgically Unresectable Urothelial Cancer MedDRA version: 20.0 Level: PT Classification code 10005003 Term: Bladder cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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. Stage IV disease (metastatic or surgically unresectable, cT4b, N+, or M+ cancer). 4. Meet appropriate molecular eligibility criteria (as determined by central laboratory screening). 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. Subjects must have available tumor tissue for molecular eligibility determination, and PD-L1 testing. 5. Documented progression of disease per RECIST 1.1, defined as any progression that requires a change in treatment, prior to randomization. 6. Prior systemic therapy: Phase 1b: Any number of lines of prior therapy. Phase 2: Progressed after 1 or 2 lines of prior chemotherapy 7. ECOG performance status (PS) grade of : 0 or 1. 8. Clinical laboratory values at screening for Hematology, Chemistry and Cardiovascular: Please refer to the study protocol 9. Before the first dose of study drug: Women of childbearing potential and fertile men who are sexually active must agree to use a highly effective method of contraception (<1%/year failure rate) 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 (ova, oocytes) 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. Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes, a woman must begin a highly effective method of contraception, as described throughout the inclusion criteria. If reproductive status is questionable, additional evaluation should be considered. It should be noted that interaction between hormonal contraception and the combination of the study drugs have not been studied. Therefore, it is unknown whether the study drugs may reduce the efficacy of the contraceptive method. – Sexual abstinence (True sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of true sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, po
Exclusion criteria
Exclusion criteria: 1. 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, subjects who have received the following prior antitumor therapy: - Received nitrosoureas and mitomycin C within 6 weeks. 2. Chemotherapy within 3 weeks of Cycle 1 Day 1. 3. Prior anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy. 4. Active malignancies (ie, requiring treatment change in the last 24 months) other than urothelial cancer (except skin cancers within the last 24 months that are considered completely cured). 5. Symptomatic central nervous system metastases. 6. Prior FGFR inhibitor treatment. 7. Radiation therapy 480 milliseconds). c. Pulmonary embolism or other venous thromboembolism within the preceding 2 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 (eg, compromise the well-being) 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. Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy). 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 erdafitinib or JNJ-63723283 or their excipients 16. Corneal or retinal abnormality likely to increase risk of eye toxicity such as but not but not limited to: - History of or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO). - Active wet, age related macular degeneration. - Diabetic retinopathy with macular edema. - Uncontrolled glaucoma (as per local standard of care). - Corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflamma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b (Dose Escalation) - To identify the RP2D and schedule of erdafitinib in combination with JNJ-63723283 Phase 2 - To evaluate the safety and clinical activity of erdafitinib alone and in combination with JNJ-63723283;Secondary Objective: Phase 1b and 2 - To characterize the PK of erdafitinib and JNJ-63723283 - To assess the immunogenicity of JNJ-63723283 Phase 2 - To further assess safety at the R2PD of erdafitinib alone and in combination with JNJ-63723283 - To further characterize the clinical activity of erdafitinib alone and in combination with JNJ-63723283;Primary end point(s): Phase 1b (Dose Escalation) - Incidence of DLT - Incidence of AEs Phase 2 - ORR (PR or better) per RECIST 1.1 - Incidence of AEs;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b and 2 - Plasma erdafitinib and serum JNJ-63723283 concentrations. - Population PK parameters and metrics of systemic exposure of erdafitinib and JNJ-63723283 - Detection of antibodies to JNJ-63723283 and effects on serum JNJ-63723283 levels Phase 2 - Incidence of AEs, SAEs and laboratory values - Duration of response (DoR) - Time to response (TTR) - Progression-free survival (PFS) - OS - ORR per immune-related RECIST (iRECIST) criteria;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Belgium, France, Germany, Israel, Italy, Korea, Republic of, Russian Federation, Spain, United Kingdom, United States
Contacts
Public Contact-
PAREXEL International LLC
Outcome results
None listed