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Brief Title: Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer

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

INTRODUCTION

  • Org Study ID: CR108445
  • Secondary ID: 2017-001980-19, 42756493BLC2002
  • NTC ID: NCT03473743
  • Sponsor: Janssen Research & Development, LLC

BRIEF SUMMARY

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.

  • Overall Status
    Recruiting
  • Start Date
    April 5, 2018
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT)

Primary Outcome 1 - Timeframe: Up to 8 weeks

Primary Outcome 2 - Measure: Phase 2: Overall Response Rate (ORR) (Partial Response [PR] or Better) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment

Primary Outcome 2 - Timeframe: Up to 2 years

Primary Outcome 3 - Measure: Phase 2: Number of Participants with Adverse Event (AEs)

Primary Outcome 3 - Timeframe: Up to 2 years

CONDITION

  • Urothelial Carcinoma

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Janssen Research & Development, LLC Clinical Trial

Role: Study Director

Affiliation: Janssen Research & Development, LLC

Overall Contact

Name: Janssen Research & Development, LLC Clinical Trial

Phone: 844-434-4210

Email: Participate-In-This-Study@its.jnj.com

LOCATION

Facility Status Contact
Facility: ULB Hôpital Erasme
Bruxelles, 1070
Belgium
Status: Recruiting Contact: N/A
Facility: Az Groeninge
Kortrijk, 8500
Belgium
Status: Recruiting Contact: N/A
Facility: CHU de Liège - Domaine Universitaire du Sart Tilman
Liege, 4000
Belgium
Status: Recruiting Contact: N/A
Facility: AZ Nikolaas - Campus Sint-Niklaas Moerland
Sint-Niklaas, 9100
Belgium
Status: Recruiting Contact: N/A
Facility: Institut de Cancerologie de Ouest (ICO) Site Paul Papin
Angers Cedex 02, 49055
France
Status: Recruiting Contact: N/A
Facility: Centre Francois Baclesse
Caen, 14000
France
Status: Recruiting Contact: N/A
Facility: Centre Leon Bérard
Lyon, 69008
France
Status: Recruiting Contact: N/A
Facility: APHM Hopital Timone
Marseille, 13005
France
Status: Recruiting Contact: N/A
Facility: Hôpital Européen Georges Pompidou
Paris, 75015
France
Status: Recruiting Contact: N/A
Facility: Clinique Sainte Anne
Strasbourg, 67000
France
Status: Recruiting Contact: N/A
Facility: CHRU de Tours
Tours, 37044
France
Status: Recruiting Contact: N/A
Facility: Institut de Cancérologie de Lorraine
Vandoeuvre lès Nancy, 54519
France
Status: Recruiting Contact: N/A
Facility: Institut Gustave Roussy
Villejuif, 94800
France
Status: Recruiting Contact: N/A
Facility: Ospedale Di Zona B Ramazzini
Carpi, 41012
Italy
Status: Recruiting Contact: N/A
Facility: PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
Lecco, 23900
Italy
Status: Recruiting Contact: N/A
Facility: IRCCS Ospedale San Raffaele
Milano, 20132
Italy
Status: Recruiting Contact: N/A
Facility: ASST Grande Ospedale Metropolitano Niguarda
Milano, 20162
Italy
Status: Recruiting Contact: N/A
Facility: Przychodnia Lekarska KOMED Roman Karaszewski
Konin, 62-500
Poland
Status: Recruiting Contact: N/A
Facility: LUX MED Onkologia Sp. z o.o.
Warszawa, 01-748
Poland
Status: Recruiting Contact: N/A
Facility: Hosp. Clinic I Provincial de Barcelona
Barcelona, 08036
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Univ. Ramon Y Cajal
Madrid, 28034
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Clinico San Carlos
Madrid, 28040
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Univ. Fund. Jimenez Diaz
Madrid, 28050
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Univ. Hm Sanchinarro
Madrid, 28050
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Virgen de La Victoria
Málaga, 29010
Spain
Status: Recruiting Contact: N/A
Facility: Complexo Hosp. Univ. de Ourense
Ourense, 32005
Spain
Status: Recruiting Contact: N/A
Facility: Corporacio Sanitari Parc Tauli
Sabadell, 08208
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Univ. Marques de Valdecilla
Santander, 39008
Spain
Status: Recruiting Contact: N/A
Facility: H. Clinico Universitario de Santiago de Compostela
Santiago de Compostela, 15706
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Virgen Macarena
Sevilla, 41009
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Virgen Del Rocio
Sevilla, 41013
Spain
Status: Recruiting Contact: N/A
Facility: Instituto Valenciano de Oncologia
Valencia, 46009
Spain
Status: Recruiting Contact: N/A
Facility: Hosp. Clinico Univ. de Valencia
Valencia, 46010
Spain
Status: Recruiting Contact: N/A
Facility: Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301
Taiwan
Status: Recruiting Contact: N/A
Facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung, 807
Taiwan
Status: Recruiting Contact: N/A
Facility: China Medical University Hospital
Taichung City, 40447
Taiwan
Status: Recruiting Contact: N/A
Facility: National Cheng Kung University Hospital
Tainan, 70403
Taiwan
Status: Recruiting Contact: N/A
Facility: National Taiwan University Hospital
Taipei City, 10002
Taiwan
Status: Recruiting Contact: N/A
Facility: Chang-Gung Memorial Hospital, LinKou Branch
Taoyuan, 333
Taiwan
Status: Recruiting Contact: N/A
Facility: Adnan Menderes University Training and Research Hospital
Aydin, 09100
Turkey
Status: Recruiting Contact: N/A
Facility: Trakya University Medical Faculty
Edirne, 22030
Turkey
Status: Recruiting Contact: N/A
Facility: Istanbul University Cerrahpasa Medical Faculty
Istanbul, 34096
Turkey
Status: Recruiting Contact: N/A
Facility: Ege University
Izmir, 35100
Turkey
Status: Recruiting Contact: N/A
Facility: Necmettin Erbakan University Meram Medical Faculty
Konya, 61080
Turkey
Status: Recruiting Contact: N/A
Facility: St Bartholomew's Hospital
London, NW1 2PG
United Kingdom
Status: Recruiting Contact: N/A