Description:
The purpose of this study is to: (a) characterize the safety and tolerability of and to
identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with
cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and
carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of
erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants
with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth
factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.
Title
- Brief Title: A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer
- Official Title: A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer
Clinical Trial IDs
- ORG STUDY ID:
CR108445
- SECONDARY ID:
2017-001980-19
- SECONDARY ID:
42756493BLC2002
- NCT ID:
NCT03473743
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Erdafitinib | JNJ-42756493 | Phase 1b: Dose Escalation |
Cetrelimab | JNJ-63723283 | Phase 1b: Dose Escalation |
Cisplatin | | Phase 1b: Dose Escalation |
Carboplatin | | Phase 1b: Dose Escalation |
Purpose
The purpose of this study is to: (a) characterize the safety and tolerability of and to
identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with
cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and
carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of
erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants
with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth
factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.
Detailed Description
This open-label (all people know identity of intervention) and multicenter (when more than
one hospital or medical school team work on a medical research study) study to establish the
recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or
carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with
cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of
the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with
advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene
alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have
received any number of lines of prior therapy, and participants enrolled in Phase 1b
erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic
therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior
systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose
Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib +
cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose
Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib +
cetrelimab combination to further characterize safety and clinical activity. The study will
be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study
evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers,
and safety.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | - Erdafitinib
- Cetrelimab
- Cisplatin
- Carboplatin
|
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). | |
Eligibility Criteria
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 (>) 30 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
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT) |
Time Frame: | Up to 8 weeks |
Safety Issue: | |
Description: | The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher. |
Secondary Outcome Measures
Measure: | Phase 1b and Phase 2: Plasma Concentration of Erdafitinib |
Time Frame: | Cycle(C)1 Day(D)1 up to C3D1 (each cycle of 28 days) |
Safety Issue: | |
Description: | Plasma concentrations will be reported for erdafitinib. |
Measure: | Phase 1b and Phase 2: Serum Concentration of Cetrelimab |
Time Frame: | Up to Follow-up (approximately up to 2 years) |
Safety Issue: | |
Description: | Serum concentrations will be reported for cetrelimab. |
Measure: | Phase 1b: Plasma Concentration of Platinum (Cisplatin and Carboplatin) Chemotherapy |
Time Frame: | C1D1 up to C4D1 (each cycle of 21 days) |
Safety Issue: | |
Description: | Plasma concentrations will be reported for platinum (cisplatin and carboplatin) chemotherapy. |
Measure: | Phase 1b and Phase 2: Number of Participants with Anti-Cetrelimab Antibodies |
Time Frame: | Up to Follow-up (approximately up to 2 years) |
Safety Issue: | |
Description: | Number of participants with anti-cetrelimab antibodies will be reported. |
Measure: | Phase 2: Number of Participants with Serious Adverse Events (SAEs) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. |
Measure: | Phase 2: Number of Participants with Abnormal Laboratory Values |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Number of participants with abnormal laboratory values will be reported. |
Measure: | Phase 2: Duration of Response (DoR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | DoR is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. |
Measure: | Phase 2: Time to Response (TTR) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | TTR is defined as the time from the date of randomization to the date of initial documentation of a response (CR or PR). |
Measure: | Phase 2: Progression-Free Survival (PFS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | PFS is defined as the duration from the date of randomization until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first. |
Measure: | Phase 2: Overall Survival (OS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | OS is defined as the time from the date of randomization to the date of the participant's death. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 13, 2021