Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication BALVERSA is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA [see Dosage and Administration (2.1) and Clinical Studies (14.1) ] . FDA label
Also known as JNJ-42756493 Tablet, JNJ-42756493 (erdafitinib), Erdafitinib, TAR-210, Erdafitinib Intravesical Delivery System, Balversa
JNJ-42756493 · 14 trials · 58 indications
DFS is measured as the time from randomization to the date of the first recurrence of HR-NMIBC (high-grade Ta, any T1 or carcinoma in situ \[CIS\]), progression, or death due to any cause, whichever occurs first.
DFS is measured as the time from randomization to the date of the first documented recurrence of Ta non-muscle invasive bladder cancer (NMIBC) of any grade, disease progression, or death due to any cause, whichever occurs first.
Overall survival was measured from the date of randomization to the date of the participant's death.
RFS was defined as the time from the date of randomization until the date of the reappearance of high-risk disease (high-grade Ta, T1 or carcinoma in situ \[CIS\]), or death, whichever was reported first. Recurrence was assessed using cystoscopy, bladder mapping, urine cytology, and computed tomography (CT)/ magnetic resonance imaging (MRI) urogram. Participants who were recurrence-free and alive or had unknown status were censored at the last tumor assessment. The Kaplan-Meier method was used to estimate the distribution of overall RFS for each treatment group.
ORR is defined as the percentage of participants who achieved a complete response (CR), or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information.
ORR is defined as the percentage of participants who achieved a CR, or PR based on RANO criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information. The core panel cohort is a subgroup of the broad panel cohort with a select panel of pre-specified FGFR markers: FGFR3 mutations (S249C;Y373C; R248C; G370C); FGFR2 mutations (C382R); FGFR3 fusions (FGFR3-TACC3); FGFR2 fusions (FGFR2-BICC1; FGFR2-TACC2).
Match rate will be calculated as the percent of eligible patients who have an actionable mutation of interest and are matched to at least one of the subprotocols, and confidence intervals will be constructed using the Wilson score interval method. Patients enrolled on or after Amendment 4 will not be included in this analysis as screening of unselected patients will no longer be conducted.
Objective Response Rate (ORR) is defined as proportion of participants with best objective response of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) criteria.
Percentage of participants with best (overall) objective response were reported. Best objective response is defined as the best (overall) objective response a participants achieved during the study in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), where CR and PR were confirmed as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. As per RECIST version 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responders are participants with BOR of CR or PR.
Cmax is the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Cmax is the maximum observed plasma concentration of 1-OH-Midazolam (midazolam metabolite) alone or in combination with erdafitinib.
Cmax is the maximum observed plasma concentration of metformin alone or in combination with erdafitinib
Tmax is the time to reach the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Tmax is the time to reach the maximum observed plasma concentration of 1-OH-Midazolam alone or in combination with erdafitinib.
Tmax is the time to reach maximum observed plasma concentration of metformin alone or in combination with erdafitinib
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of midazolam alone or in combination with erdafitinib.
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of 1-OH-Midazolam alone or in combination with erdafitinib.
AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of metformin alone or in combination with erdafitinib.
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of midazolam alone or in combination with erdafitinib.
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of 1-OH-Midazolam alone or in combination with erdafitinib.
AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of metformin alone or in combination with erdafitinib
Number of participants with DLT will be assessed. The DLTs are specific adverse events related to erdafitinib intravesical delivery system and are defined as any of the following: high grade non-hematologic toxicity or hematologic toxicity.
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Overall CR is defined as the negative cystoscopy or positive cystoscopy with centrally reviewed biopsy negative for malignancy.
Number of participants with DLTs were reported. The DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE version 5.0) are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) non-hematological toxicity or hematological toxicity.
ORR is defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version1.1. As per RECIST version 1.1, CR: disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR: greater than or equal to (\>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.
Number of participants with TEAEs were reported. An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as adverse events with onset or worsening on or after date of first dose of study treatment.
RP2D will be determined based on pharmacodynamics, biomarker response or clinical response, as well as the incidence rate and nature of the toxicities observed.
Objective response based on assessment of confirmed Complete response (CR) or partial response (PR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC. CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response.
The maximum tolerated dose as determined in Part 1 of the study will be used as the recommended dose for Part 2, 3 and Part 4.
| Arm | Type | Description |
|---|---|---|
| Group A: TAR-210 | EXPERIMENTAL | Participants in Group A will have TAR-210 inserted in the bladder on Day 1. TAR-210 will be inserted over a treatment duration of approximately 2 years. |
| Group B: Mitomycin C (MMC) or Gemcitabine | ACTIVE_COMPARATOR | Participants in Group B will receive intravesical mitomycin C (MMC) or gemcitabine (investigator's choice) once weekly for 4 to 6 induction doses followed by maintenance dosing once monthly for up to 1 year. An optional second year of additional maintenance can be added at the investigator's discretion. |
| Main Study: Group A: TAR-210 | EXPERIMENTAL | Participants in Group A will have TAR-210 inserted in the bladder on Day 1 and removed after 12 weeks. One TAR-210 will be inserted every 12 weeks over a treatment period of approximately 1 year. |
| Main Study: Group B: MMC or Gemcitabine | ACTIVE_COMPARATOR | Participants in Group B will receive intravesical mitomycin C (MMC) or gemcitabine (investigator's choice) once weekly for 4 to 6 induction doses followed by a maintenance phase for a minimum of 6 months and up to 1 year. |
| Substudy: Group A: TAR-210 | EXPERIMENTAL | Participants in Group A will have TAR-210 inserted in the bladder on Day 1 and removed after 12 weeks. One TAR-210 will be inserted every 12 weeks over a treatment period of approximately 1 year. |
| Substudy: Group B: MMC | ACTIVE_COMPARATOR | Participants in substudy Group B will receive intravesical MMC once weekly for 4 to 6 induction doses followed by a maintenance phase for a minimum of 6 months and up to 1 year. |
| Cohort 1 (Arm 1A): Erdafitinib | EXPERIMENTAL | Participants will be screened based on Fibroblast Growth Factor Receptor Inhibitor Clinical Trial Assay (FGFRi CTA) to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-programmed cell death protein PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 milligram (mg), once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustment are based on phosphate level and observed toxicity (adverse events \[AEs\]). Participants who enter in Long-term extension (LTE) phase will continue to receive the erdafitinib tablet as per investigator's decision. |
| Cohort 1 (Arm 1B): Vinflunine or Docetaxel | EXPERIMENTAL | Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-PD-\[L\] 1 agent) will receive vinflunine 320 milligram per meter square (mg/m\^2) as a 20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion every 3 weeks. Treatment with either agent (choice of investigator) will be administered until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive Vinflunine or Docetaxel until the participant can commercially receive chemotherapy within the local healthcare system. |
| Cohort 2 (Arm 2A): Erdafitinib | EXPERIMENTAL | Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 mg, once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on phosphate level and observed toxicity (AEs). Participants who enter in LTE phase will continue to receive the erdafitinib tablet as per investigator's decision. |
| Cohort 2 (Arm 2B): Pembrolizumab | EXPERIMENTAL | Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive the pembrolizumab until 2 years after the first dose of pembrolizumab (at start of study) or until the participant can commercially receive pembrolizumab within the local healthcare system, whichever comes first. |
| Cohort 1: Erdafitinib | EXPERIMENTAL | Participants with high-risk non-muscle-invasive bladder cancer (NMIBC) presenting as papillary tumor only (carcinoma in situ \[CIS\], absent), with disease recurrence after bacillus Calmette- Guerin (BCG) therapy will receive treatment with erdafitinib. |
| Cohort 1: Investigators Choice | ACTIVE_COMPARATOR | Participants with high-risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy will receive the investigator's choice of either intravesical gemcitabine or intravesical mitomycin C (MMC) or hyperthermic MMC. Participants who are randomized to gemcitabine or MMC or hyperthermic MMC in Cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib. |
| Cohort 2 | EXPERIMENTAL | Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib. |
| Cohort 3 | EXPERIMENTAL | Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib. |
| Erdafitinib | EXPERIMENTAL | Participants with fibroblast growth factor receptor (FGFR) mutations and FGFR gene fusions will receive a dose of erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment, or end of data collection timepoint if there is clinical benefit in the opinion of the investigator, has been achieved. |
| Subprotocol A (NTRK1, NTRK2, or NTRK3 gene fusion) | EXPERIMENTAL | Patients with a NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib sulfate PO or via nasogastric- or gastric-tube BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol B (FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation) | EXPERIMENTAL | Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study. |
| Subprotocol C (EZH2, SMARCB1, or SMARCA4 gene mutation) | EXPERIMENTAL | Patients with an EZH2, SMARCB1, or SMARCA4 gene mutation receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol D (TSC1, TSC2, or PI3K/mTOR gene mutation) | EXPERIMENTAL | Patients with a TSC1, TSC2, or PI3K/mTOR gene mutations receive PI3K/mTOR inhibitor LY3023414 PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol E (activating MAPK pathway gene mutation) | EXPERIMENTAL | Patients with an activating MAPK pathway gene mutation receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol F (ALK or ROS1 gene alteration) | EXPERIMENTAL | Patients with an ALK or ROS1 gene alteration receive ensartinib PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan, MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy during screening and on study. Patients also undergo blood sample collection on study. |
| Subprotocol G (BRAF V600 gene mutation) | EXPERIMENTAL | Patients with a BRAF V600 gene mutation receive vemurafenib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol H (ATM, BRCA1, BRCA2, RAD51C, RAD51D mutations) | EXPERIMENTAL | Patients deleterious ATM, BRCA1, BRCA2, RAD51C, or RAD51D gene mutations receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol I (Rb positive, alterations in cell cycle genes) | EXPERIMENTAL | Patients with Rb positive advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with activating alterations in cell cycle genes receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol J (MAPK pathway mutations) | EXPERIMENTAL | Patients with MAPK pathway mutations receive ulixertinib PO BID. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol K (IDH1 gene mutation) | EXPERIMENTAL | Patients with IDH1 gene mutations receive ivosidenib PO QD. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. |
| Subprotocol M (HRAS gene alterations) | EXPERIMENTAL | Patients receive tipifarnib PO or via nasogastric or gastric tube BID on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. |
| Subprotocol N (activating RET mutations) | EXPERIMENTAL | Patients with activating RET gene alterations receive selpercatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT, PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial. |
| Erdafitinib (8 milligram) | EXPERIMENTAL | Prior to interim analysis 1 (IA1), there were 2 treatment regimens: Regimen 1 (10 milligram \[mg\] once daily, 7 days on/7 days off); and Regimen 2 (6 mg once daily for 28 days). Following IA1, Regimen 1 is closed for further enrollment and starting dose of Regimen 2 is increased to 8 mg once daily for 28 days on a 28-day cycle (referred to as Regimen 3). Participants who enrolled in DDI substudy will receive pretreatment with single doses of midazolam (Day -2) and metformin (Day -1). Participants enrolled in DDI substudy will receive 8 mg erdafitinib treatment from Day 1 to Day 15, single doses of midazolam 2.5 mg (Day 13) and metformin 1000 mg (Day 14) and erdafitinib treatment will continued until disease progression. Participants who completed the DDI substudy and continue to benefit from erdafitinib treatment, will continue to receive erdafitinib in long-term extension (LTE) phase. |
| Dose Escalation: Erdafinitib Intravesical Delivery System | EXPERIMENTAL | Participants with bladder cancer and fibroblast growth factor receptor (FGFR) mutations or fusions will receive erdafitinib intravesical delivery system and study will evaluate 2 dose levels of erdafitinib. Participants with a complete response (CR) may continue to receive treatment up to a duration of 1 year as long as there is no disease recurrence or progression, intolerable toxicity or withdrawal of consent. |
| Part 1: Dose Escalation | EXPERIMENTAL | Participants with recurrent, bacillus Calmette-Guerin (BCG)-experienced high risk papillary-only Non-Muscle-Invasive Bladder Cancer (NMIBC), refusing or ineligible for radical cystectomy or with recurrent, intermediate-risk NMIBC will receive Erdafitinib Intravesical Delivery System. The dose will be escalated to determine preliminary recommended phase 2 dose(s) (RP2D\[s\]) for Part 2. |
| Part 2: Dose Expansion | EXPERIMENTAL | Participants in each of 5 disease-specific NMIBC or MIBC cohorts may be enrolled at one or more dose levels that have been determined to be safe in Part 1. |
| Part 3: RP2D Dose Expansion | EXPERIMENTAL | Participants in 2 of the disease-specific NMIBC cohorts (cohorts 1 and 3) may be enrolled at RP2D to determine the safety, evaluate PK and preliminary clinical activity. |
| Part 4: Phase 2 Expansion | EXPERIMENTAL | Participants with recurrent IR-NMIBC will be enrolled in this part to further evaluate the safety, efficacy, and PK of the selected RP2D. |
| Phase 1b: Dose Escalation | EXPERIMENTAL | Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. |
| Phase 2: Dose Expansion | EXPERIMENTAL | The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV). |
| Part 1: Dose Escalation and Part 2: Dose Expansion | EXPERIMENTAL | Part 1: First, participants will receive 8 milligram (mg) (starting dose) tablet of JNJ-42756493 (erdafitinib) orally once daily from Day 1 to 7, then Day 15 to 21 of 28 days cycle or 8 mg orally once daily from Day 1 to 21 of 28 days cycle (intermittent dosing). After recommended Phase 2 dose (RP2D) is identified, enrollment of continuous dosing schedule will be open, starting at 8mg. In this cohort, participants will receive 8mg (starting dose) tablet of JNJ42756493 (erdafitinib) orally once daily from Day 1 to Day 28 in a 28-day cycle. Dose of the study medication will be escalated sequentially till the dose limiting toxicity is achieved to determine RP2D. Part 2: Participants will receive RP2D JNJ-42756493 (erdafitinib) dose determined in Part 1. Participants who are tolerating study drug treatment and achieve clinical responses or stable disease will continue to receive study drug at the same dose until disease progression, unacceptable toxicity, or withdrawal of consent. |
| Part 1: Dose Escalation (Daily Dosing) | EXPERIMENTAL | Dose escalation of JNJ-42756493 is to occur until a dose at which \<33 percent of participants experience a dose-limiting toxicity, the maximum concentration of JNJ-42756493 is less than the protocol-defined cardiovascular threshold, and JNJ-42756493 is biologically active. Participants will receive study drug once day on Day 1 of Cycle 1 followed by a 2-day drug-free period (Days 2 and 3 of Cycle 1) and continues throughout the 21 day cycle. For all subsequent cycles once a day for 21 days. |
| Part 1: Dose Escalation (Intermittent Dosing) | EXPERIMENTAL | Intermitting dosing regimen will be 28 days (7 days on and 7 days off). Participants will receive JNJ-42756493 on Days 1 to 7 and Days 15 to 21 of each cycle; JNJ-42756493 will not be administered on Days 8 to 14 and Days 22 to 28 of each cycle. |
| Part 1 | EXPERIMENTAL | Dose Escalation, Part 1: Participants will be enrolled in sequential cohorts to determine recommended Phase 2 doses (RP2D). |
| Part 2 | EXPERIMENTAL | Dose Confirmation, Part 2: Tumor biopsy cohorts will confirm RP2D. |
| Part 3, Cohort A | EXPERIMENTAL | First dose expansion, Part 3: Participants with squamous non-small cell lung cancer. |
| Part 3, Cohort B | EXPERIMENTAL | First dose expansion, Part 3: Participants with small cell lung cancer. |
| Part 3, Cohort C | EXPERIMENTAL | First dose expansion, Part 3: Participants with breast cancer. |
| Part 3, Cohort D | EXPERIMENTAL | First dose expansion, Part 3: Participants with solid tumors (consisting of one of the following: gastric, head and neck, lung adenocarcinoma, urothelial, glioblastoma multiforme \[GBM\], ovarian or prostate). |
| Part 4, Cohort E | EXPERIMENTAL | Second dose expansion, Part 4: Participants with non-small cell lung cancer. |
| Part 4, Cohort F | EXPERIMENTAL | Second dose expansion, Part 4: Participants with solid tumors (consisting of one of the following: breast, urothelial, GBM). |
| Name | Type | Description |
|---|---|---|
| TAR-210 | DRUG | TAR-210 will be administered intravesically. |
| Mitomycin C | DRUG | MMC will be administered intravesically. |
| Gemcitabine | DRUG | Gemcitabine will be administered intravesically. |
| MMC | DRUG | MMC will be administered intravesically. |
| Erdafitinib | DRUG | Participants will swallow erdafitinib tablets orally at a starting dose of 8 mg. |
| Vinflunine | DRUG | Participants will receive vinflunine 320 mg/m\^2 as a 20-minute intravenous infusion. |
| Docetaxel | DRUG | Participants will receive docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion. |
| Pembrolizumab | DRUG | Participants will receive pembrolizumab 200 mg as a 30-minute intravenous infusion. |
| Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA) | DEVICE | FGFRi CTA will be used to determine molecular eligibility. |
| Investigator Choice (Gemcitabine) | DRUG | Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months. |
| Investigator Choice (Mitomycin C) | DRUG | Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months. |
| Biopsy Procedure | PROCEDURE | Undergo biopsy |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Bone Marrow Aspiration and Biopsy | PROCEDURE | Undergo a bone marrow and/or biopsy |
| Bone Scan | PROCEDURE | Undergo a bone scan |
| Computed Tomography | PROCEDURE | Undergo CT, PET/Ct, and/or CT/MRI |
| Ensartinib | DRUG | Given PO |
| Ivosidenib | DRUG | Given PO |
| Laboratory Biomarker Analysis | OTHER | Undergo molecular analysis |
| Larotrectinib Sulfate | DRUG | Given PO or via nasogastric- or gastric-tube |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI, PET/MRI, and/or CT/MRI |
| Mutation Carrier Screening | PROCEDURE | Undergo tumor tissue mutation screening |
| Olaparib | DRUG | Given PO |
| Palbociclib | DRUG | Given PO |
| Pharmacological Study | OTHER | Correlative studies |
| Positron Emission Tomography | PROCEDURE | Undergo PET, PET/CT, and/or PET/MRI |
| Radionuclide Imaging | PROCEDURE | Undergo radionuclide imaging |
| Samotolisib | DRUG | Given PO |
| Selpercatinib | DRUG | Given PO |
| Selumetinib Sulfate | DRUG | Given PO |
| Tazemetostat | DRUG | Given PO |
| Tipifarnib | DRUG | Given PO or via nasogastric or gastric tube |
| Ulixertinib | DRUG | Receive PO |
| Vemurafenib | DRUG | Given PO |
| X-Ray Imaging | PROCEDURE | Undergo an x-ray |
| Midazolam | DRUG | Participants who enrolled in DDI substudy will receive pretreatment with single dose of midazolam on Day -2 and single dose of midazolam on Day 13. |
| Metformin | DRUG | Participants who enrolled in DDI substudy will receive pretreatment with single dose of metformin on Day -1 and single dose of metformin on Day 14. |
| Erdafitinib Intravesical Delivery System | DRUG | Erdafitinib intravesical delivery system will be administered. |
| Cetrelimab | DRUG | Participants will receive cetrelimab by intravenous infusion. |
| Cisplatin | DRUG | Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy. |
| Carboplatin | DRUG | Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy. |
| JNJ-42756493 (erdafitinib) | DRUG | Part 1: Participants will receive 8 mg tablet once daily from Day 1 to 7, and then Day 15 to 21 of 28 days cycle or 8 mg orally once daily of 28 days cycle up to the maximum tolerated dose in order to determine the recommended Phase 2 dose. Part 2: Recommended Phase 2 JNJ-42756493 (erdafitinib) dose determined in Part 1. |
| Part 1: JNJ-42756493 | DRUG | JNJ-42756493 dose escalation starting at dose of 2 mg orally daily for 21-day cycles and 28 day cycles Intermitting dosing regimen (7 days on and 7 days off) up to the maximum tolerated dose in order to determine the recommended Phase 2 dose. |
| Part 2: JNJ-42756493 | DRUG | Recommended Phase 2 JNJ-42756493 dose determined in Part 1 administered orally for 28-days cycles (Intermitting dosing regimen). |
| JNJ-42756493: Part 1 | DRUG | Participants will receive 0.5 mg (starting dose) capsule of JNJ-42756493 orally (by mouth) once daily on Day 1 of Cycle 1. Dose of the study medication will be escalated sequentially till the dose limiting toxicity is achieved to determine the recommended part 2 doses (RP2D). |
| JNJ-42756493: Part 2 | DRUG | Participants will receive JNJ-42756493 at the RP2D or below RP2D (maximum tolerated dose from Part 1) orally once daily on a 21 days cycle to confirm RP2D (in Part 2). |
| JNJ-42756493: Part 3 | DRUG | Participants will receive JNJ-42756493 at first RP2D of 9 mg daily in Part 3 orally once daily on a 21 days cycle. |
| JNJ-42756493: Part 4 | DRUG | Participants will receive JNJ-42756493 second RP2D of 10 mg intermittent dosing in Part 4 (with option to increase to 12 mg intermittent dosing based on phosphate level), orally on an intermittent schedule of daily for 7 days followed by 7 days off with a 28-day cycle. |
Inclusion criteria: * Histologically confirmed diagnosis by local pathology of papillary-only HR-NMIBC (defined as high-grade Ta or any T1, no CIS). Mixed histology tumors are allowed if urothelial differentiation is predominant. However, neuroendocrine, and small cell variants will be excluded * H...
JNJ-42756493 is an investigational small molecule developed by Johnson & Johnson for oncology. It has been studied in Phase 1 clinical trials in adults with advanced or refractory solid tumors, lymphoma, and hepatocellular carcinoma. It is also known as erdafitinib. It is not described as approved and remains in clinical development.
JNJ-42756493 has been studied in Phase 1 trials for advanced or refractory solid tumors, lymphoma, and hepatocellular carcinoma. The studied populations included adults with neoplasms, tumors or lymphoma, and hepatocellular carcinoma. It is an investigational agent and is not described as approved for any indication.
JNJ-42756493 is developed by Johnson & Johnson, which trades under the ticker JNJ. The company sponsored the Phase 1 studies of the agent in advanced or refractory solid tumors, lymphoma, and hepatocellular carcinoma. Development has been conducted across sites in the United States, Europe, and Asia.
JNJ-42756493 is in Phase 1 development. All three listed trials are Phase 1 studies, and all are completed. The program has enrolled 188 participants in its largest trial. The drug is investigational and is not described as approved for any indication.
JNJ-42756493 has been evaluated in three completed Phase 1 trials: NCT01703481 in advanced or refractory solid tumors or lymphoma (188 participants, United States, France, Spain), NCT02421185 in advanced hepatocellular carcinoma (53 participants, China, South Korea, Taiwan), and NCT01962532 in advanced or refractory solid tumors or lymphoma (19 participants, Japan).
Yes, JNJ-42756493 is also known as erdafitinib. Other listed names include JNJ-42756493 Tablet and JNJ-42756493 10 mg tablet, along with Part 1 through Part 4 study labels. Searches for erdafitinib refer to the same investigational small molecule developed by Johnson & Johnson.