A Study of B-701 in Combination With Pembrolizumab in Treatment of Locally Advanced or Metastatic Urothelial Cell Carcinoma

NCT03123055 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: B-701-U222017-001292-23
• Study Type: interventional
• Target: 28
• Locations: 16 countries
• Sites: 47

Brief Summary

This is a Phase 1b/2 multi-center, open-label study to establish the initial safety and to determine a recommended Phase 2 dose of B-701 in combination with pembrolizumab, and to determine safety, tolerability and efficacy of B-701 (vofatamab) plus pembrolizumab in the treatment of subjects with locally advanced or metastatic UCC, who have progressed following platinum-based chemotherapy and who have not received prior immune checkpoint inhibitor therapy.

Conditions

Locally Advanced or Metastatic Urothelial Cell Carcinoma; Urinary Bladder Disease; Urological Diseases

Keywords

Urothelial Cell Carcinoma; UCC; bladder cancer; B-701; FGFR3; invasive bladder cancer; Transitional Cell Carcinoma; TCC; second line therapy; monoclonal antibody; combination therapy; Phase 1b; pembrolizumab; checkpoint inhibitor; Phase 2; Urothelial Carcinoma; Vofatamab

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities Within a Period of 35 Days

  Number of Participants with Dose Limiting Toxicities within a period of 35 days will be analyzed reviewing the aggregate of adverse events (AEs) and serious adverse events (SAEs) by the B-701 program Safety Oversight Committee and will result in a recommended Phase 2 dose. Six subjects at a time are enrolled and observed for 35 days after the initial dose. If 2 or more subjects experience a DLT that dose will be declared intolerable and de-escalation of the dose will occur.

  1 year

• Number of Subjects Experiencing Adverse Events (AEs and SAEs)

  Evaluate the safety and tolerability of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as assessed by number of subjects experiencing adverse events (AEs and SAEs), physical examination findings, laboratory test results, and vital signs over time. This outcome is measured by a safety monitoring committee who regularly met and reviewed aggregate trends of reports AEs, lab ranges, physical exams etc. and determined if the drug was safe to continue.

  2.5 years

• Efficacy of B-701 (Vofatamab) Plus Pembrolizumab Measured by ORR

  Evaluate the efficacy of B-701 (vofatamab) plus pembrolizumab in subjects with UCC as measured by objective response rate (ORR) by RECIST 1.1. ORR is defined as the percentage of subjects who have baseline measurable disease and who achieve a best response of either complete response (CR) or partial response (PR).

  2 years

Secondary Outcomes (6)

• Assessment of Changes in Biomarkers Induced by B-701 (Vofatamab)

  2.5 years

• Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DOR

  2 years

• Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by DCR

  2 years

• Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by PFS

  2 years

• Efficacy of B-701 (Vofatamab) in Combination With Pembrolizumab as Measured by OS

  2.5 years

Other Outcomes (2)

• PK Analysis of B-701 (Vofatamab)

  2 years

• Immunogenicity of B-701 (Vofatamab)

  2 years

Study Arms (2)

B-701 (vofatamab)

EXPERIMENTAL

B-701 (vofatamab, 25 mg/kg) will be administered via IV infusion on Cycle 0 Day 1 for a single 14-day cycle.

Drug: B-701

B-701 (vofatamab) plus pembrolizumab

EXPERIMENTAL

B-701 (vofatamab, 25 mg/kg \[or the recommended Phase 2 dose if different than 25 mg/kg\]) plus pembrolizumab (200 mg) will be administered by IV infusion on Cycle 1 Day 1 once every 3 weeks.

Drug: B-701; Drug: Pembrolizumab

Interventions

B-701 DRUG

B-701 (vofatamab) is a human IgG1 monoclonal antibody that is highly specific for the FGFR3 receptor.

Also known as: MFGR1877S, Vofatamab

B-701 (vofatamab); B-701 (vofatamab) plus pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is a humanized antibody used in cancer immunotherapy. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.

Also known as: Keytruda

B-701 (vofatamab) plus pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including of the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
• Have progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• Have available archival tumor or be willing to undergo diagnostic biopsy at screening. Sample must be of suitable quality and quantity to satisfy group assignment and biomarker endpoints.
• Have measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.

You may not qualify if:

• Participants with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on the Screening chest CT scan.
• Prior therapy with an anti-programmed cell death 1 (PD-1) or anti-PD-Ligand 1 agent, or with an agent directed to another co-inhibitory T-cell receptor or FGFR inhibitor.
• Patients with autoimmune disease or medical conditions that required systemic corticosteroids (\> 10 mg/day prednisone or its equivalent) or other immunosuppressive medications or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment. Note: Replacement therapy (e.g. physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Primary central nervous system (CNS) malignancy or CNS metastases.
• History of clinically significant coagulation or platelet disorder in the past 12 months.

Sponsors & Collaborators

• Rainier Therapeutics: lead

Study Sites (52)

Research Site

Greenbrae, California, 94904, United States

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Fort Wayne, Indiana, 46845, United States

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Louisville, Kentucky, 40202, United States

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Washington University School of Medicine

St Louis, Missouri, 63110, United States

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Cleveland, Ohio, 44195, United States

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Philadelphia, Pennsylvania, 19107, United States

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Germantown, Tennessee, 38138, United States

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Houston, Texas, 77030, United States

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Brussels, 1000, Belgium

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Leuven, 3000, Belgium

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Yvoir, 5530, Belgium

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Copenhagen, 2100, Denmark

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Bordeaux, 33076, France

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Dijon, 21000, France

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Dresden, 01307, Germany

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Frankfurt, 60488, Germany

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Heidelberg, 69120, Germany

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Kassel, 34125, Germany

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Munich, 81377, Germany

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Münster, 48149, Germany

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Budapest, 1122, Hungary

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Milan, 20133, Italy

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Milan, 20141, Italy

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Chisinau, 2025, Moldova

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Utrecht, 3584 CX, Netherlands

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Katowice, 40-514, Poland

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Warsaw, 02-567, Poland

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Warsaw, 02-781, Poland

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Wieliszew, 05-135, Poland

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Wroclaw, 53-413, Poland

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Moscow, 125284, Russia

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Saint Petersburg, 197758, Russia

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Ufa, 450000, Russia

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Belgrade, 11000, Serbia

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Belgrade, 11070, Serbia

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Kamenitz, 21204, Serbia

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Kragujevac, 34000, Serbia

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Niš, 18000, Serbia

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Gwangju, 61469, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Madrid, CA, 28050, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Uppsala, 75185, Sweden

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Ankara, 06100, Turkey (Türkiye)

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Antalya, 07059, Turkey (Türkiye)

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Dnipro, 49102, Ukraine

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Kyiv, 03022, Ukraine

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MeSH Terms

Conditions

Urinary Bladder Diseases; Urologic Diseases; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

B701 protein, Human herpesvirus 6; vofatamab; pembrolizumab

Condition Hierarchy (Ancestors)

Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Rainier Therapeutics

Sabella@RainierRx.com

510-878-2486

Study Officials

• Rainier Therapeutics

  Rainier Therapeutics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: B-701 (vofatamab) as monotherapy for first 2 weeks followed by B-701 (vofatamab) in combination with pembrolizumab thereafter.

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 21, 2017
• Study Start: April 20, 2017
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: March 18, 2020
• Results First Posted: March 18, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); BE (3); IT (2); SE (1); RU (3); US (8); FR (2); TU (2); UA (2); PL (5); HU (1); MO (1); DK (1); KR (4); NL (1); DE (6)