Clinical Trials /

Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma

NCT03473756

Description:

FORT-2 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study comprises two separate parts: Phase 1b (Part A) and Phase 2 (Part B).The study parts differ in design, objectives and treatment. The primary objectives of this Phase 1b study (Part A) are to determine the safety, tolerability,RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in these patients. The primary objective of the Part B is to compare progression-free survival (PFS) according to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic urothelial carcinoma. Of note, patients who participate in Part A are not allowed to participate in Part B. Part B will be initiated once the data from Part A supports continuation of the study, even if this occurs prior to primary completion of Part A. The sponsor may decide not to continue the study as a whole after completion of Part A if the data do not support further development.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab in Urothelial Carcinoma
  • Official Title: An International, Multicenter, Phase 1b/2 Study of Rogaratinib (BAY1163877) in Combination With Atezolizumab as First-line Treatment in Cisplatin-ineligible Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 19131
  • SECONDARY ID: 2017-001483-38
  • NCT ID: NCT03473756

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
Rogaratinib (BAY1163877)Rogaratinib + Atezolizumab in Part A
AtezolizumabRogaratinib + Atezolizumab in Part A
PlaceboPlacebo + Atezolizumab

Purpose

Study 19131 is designed to evaluate safety, efficacy, RP2D and PK of rogaratinib in combination with atezolizumab in patients with untreated FGFR-positive urothelial carcinoma. The study comprises two separate parts: Phase 1b (Part A) and Phase 2 (Part B).The study parts differ in design, objectives and treatment. The primary objectives of this Phase 1b study (Part A) are to determine the safety, tolerability,RP2D and pharmacokinetics of rogaratinib in combination with atezolizumab in these patients. The primary objective of the Part B is to compare progression-free survival (PFS) according to RECIST v1.1 of rogaratinib in combination with atezolizumab over placebo in combination with atezolizumab in untreated patients with FGFR-positive locally advanced or metastatic urothelial carcinoma. Of note, patients who participate in Part A are not allowed to participate in Part B. Part B will be initiated once the data from Part A supports continuation of the study, even if this occurs prior to primary completion of Part A. The sponsor may decide not to continue the study as a whole after completion of Part A if the data do not support further development.

Trial Arms

NameTypeDescriptionInterventions
Rogaratinib + Atezolizumab in Part AExperimentalPart A: Part A is conducted in patients who are cisplatin-ineligible and have had no prior systemic treatment for locally advanced or metastatic disease. Patients will receive rogaratinib plus atezolizumab combination treatment.
  • Rogaratinib (BAY1163877)
  • Atezolizumab
Placebo + AtezolizumabPlacebo ComparatorPart B:Patients will receive placebo in combination with atezolizumab until disease progression, unacceptable toxicity, death, consent withdrawal, or withdrawal from the study
  • Atezolizumab
  • Placebo
Rogaratinib + Atezolizumab in Part BExperimentalPart B:Patients will receive rogaratinib in combination with atezolizumab until disease progression, unacceptable toxicity, death, consent withdrawal, or withdrawal from the study
  • Rogaratinib (BAY1163877)
  • Atezolizumab

Eligibility Criteria

        Inclusion criteria:

          -  Existence of archival or fresh tumor biopsy specimen for FGFR1/3 mRNA expression
             testing

          -  High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+) in archival or
             fresh tumor biopsy specimen

          -  Documented locally advanced (T4, any N; or any T, N2-3) or metastatic urothelial
             carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis,
             ureters, urethra, meeting all of the following criteria:

          -  No prior systemic treatment for locally advanced or metastatic urothelial carcinoma.
             For patients who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation
             for urothelial carcinoma, a treatment-free interval > 12 months between the last
             treatment administration and the date of recurrence is required in order to be
             considered treatment-naïve in the metastatic setting. Prior local intra-vesical
             chemotherapy or prior local immunotherapy is allowed.

          -  Ineligibility for cisplatin-based chemotherapy as defined by any one of the following
             criteria:

               -  Impaired renal function (GFR > 30 but < 60 mL/min/1.73 m2) according to the
                  modification of diet in renal disease (MDRD) abbreviated formula

               -  Hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies

               -  Grade ≥ 2 peripheral neuropathy (i.e. sensory alteration or paresthesia including
                  tingling)

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.

        Exlusion criteria:

          -  Active symptomatic or untreated brain metastases as determined by CT or MRI evaluation
             during screening and prior radiographic assessment.

          -  History of autoimmune disease, including but not limited to myasthenia gravis,
             myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
             inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid
             syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré
             syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

          -  History or current condition of an uncontrolled cardiovascular disease including any
             of the following conditions:

               -  Congestive heart failure (CHF) NYHA Class 2 or greater, unstable angina (symptoms
                  of angina at rest) or

               -  New-onset angina (within last 3 months before the first study drug
                  administration)

               -  Myocardial infarction (MI) within past 6 months before the first study drug
                  administration

               -  Unstable cardiac arrhythmias requiring anti-arrhythmic therapy.

          -  Patients with known coronary artery disease, congestive heart failure not meeting the
             above criteria, or known left ventricular ejection fraction < 50% must be on a stable
             medical regimen that is optimized in the opinion of the treating physician, in
             consultation with a cardiologist if appropriate.

          -  Current diagnosis of any retinal disorders including retinal detachment, retinal
             pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion.

          -  Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g.
             parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis,
             paraneoplastic hypercalcemia).

          -  Concomitant therapies that are known to increase serum calcium or phosphate levels
             (i.e. antacids, phosphate-containing laxatives oral/rectal, potassium phosphate) and
             that cannot be discontinued or switched to a different medication before the first
             study drug administration

          -  Treatment with systemic corticosteroids or other systemic immunosuppressant
             medications within 2 weeks before the first study drug administration, or anticipated
             requirement for systemic immunosuppressive medications during the trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival(PFS)
Time Frame:Up to 25 months
Safety Issue:
Description:Part B Progression-free survival (PFS) is defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical, whichever is earlier) or death due to any cause, if death occurs before progression is documented. The actual date that the tumor scan was performed will be used for this calculation. If a tumor assessment is performed over more than one day (e.g. scans for chest and abdomen done on different days for the same evaluation), the earliest date will be used for the calculation of PFS. For patients without documented radiological or clinical progression or death at the time of analysis, PFS will be censored at the last actual visit date of tumor evaluation. The primary analysis of PFS will be based on assessment by independent central review.

Secondary Outcome Measures

Measure:Objective Response Rate(ORR) in Part A
Time Frame:Up to 5 months
Safety Issue:
Description:Part A:Objective response rate (ORR) is defined as the percentage of patients with complete response (CR) or partial response (PR). Patients for whom best overall tumor response is not CR or PR, as well as patients without any post-baseline tumor assessment will be considered non-responders. For all patients, the best overall tumor response will be determined locally by investigators using the RECIST criteria (v1.1).
Measure:Disease Control Rate(DCR) in Part B
Time Frame:Up to 25 months
Safety Issue:
Description:Part B:Disease control rate (DCR) is defined as the percentage of patients, whose overall best response was not progressive disease (i.e. CR, PR, SD or Non CR/Non PD).
Measure:Duration of Response(DOR) in Part B
Time Frame:Up to 25 months
Safety Issue:
Description:Part B:Duration of response (DOR) (for PR and CR) is defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e. patients with a CR or PR.
Measure:Overall Survival(OS) in Part B
Time Frame:Up to 25 months
Safety Issue:
Description:Part B:Overall survival (OS) is defined as the time from randomization to death due to any cause. Patients alive at the date of data cut-off for analysis will be censored at the last date known to be alive.
Measure:Maximal plasma concentration (Cmax) of rogaratinib in Part A
Time Frame:At cycle 1 Day 1
Safety Issue:
Description:Part A
Measure:Area under the curve(0-8) (AUC(0-8)) of rogaratinib in Part A
Time Frame:At cycle 1 Day 1
Safety Issue:
Description:Part A
Measure:Objective Response Rate (ORR) in Part B
Time Frame:Up to 25 months
Safety Issue:
Description:
Measure:Concentrations for rogaratinib in Part B
Time Frame:Cycle 1 Day 1(C1D1), C2D1, C3D1, C4D1, C5D1
Safety Issue:
Description:Part B
Measure:Concentrations for atezolizumab in Part B
Time Frame:C1D1, C1D15
Safety Issue:
Description:Part B
Measure:Number of subjects with treatment-emergent adverse events (TEAEs) in Part B
Time Frame:Up to 25 months
Safety Issue:
Description:Part B
Measure:Number of subjects with drug-related TEAEs in Part B
Time Frame:Up to 25 months
Safety Issue:
Description:Part B
Measure:Number of subjects with treatment-emergent serious adverse events(TESAEs) in Part B
Time Frame:Up to 25 months
Safety Issue:
Description:Part B
Measure:Number of subjects with significant change in vital signs, physical finding and clinical laboratory results
Time Frame:Up to 25 months
Safety Issue:
Description:Part B

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Locally advanced or metastatic urothelial carcinoma
  • Bladder cancer
  • Checkpoint inhibition
  • FGFR inhibition

Last Updated

April 16, 2018