Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib)
Condition: Neoplasms
Intervention: Rogaratinib (BAY1163877) oral solution; Rogaratinib (BAY1163877) oral tablet; Rogaratinib (BAY1163877) 800 mg BID
Intervention description: Participants received Rogaratinib oral solution as a single dose on Cycle 1 Day 1 (C1D1) and twice daily (BID) from Cycle 1 Day 3 (C1D3) onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.; Participants received Rogaratinib oral tablet as a single dose on C1D1 and BID from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.; Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 168.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase I; Dose escalation; refractory, locally advanced or metastatic solid tumor; Bladder cancer; squamous non-small cell lung cancer; pan-FGFR inhibitor; lung adenocarcinoma; head and neck cancer

Summary:

      -  This was the first study where BAY1163877 was given to humans. Impact of the study was
           to evaluate if patients with advanced solid cancers show advanced clinical benefit under
           the treatment with the pan FGFR inhibitor. Patients (all comers) received the study drug
           treatment in a dose-escalation scheme (no placebo group) to determine the safety,
           tolerability and maximum tolerated dose (MTD) of BAY1163877. The relative
           bioavailability of liquid service formulation and tablets was determined.

        -  After the MTD was defined patients with solid tumors (all comers), lung cancer (lung
           adenocarcinoma & squamous non-small cell lung cancer), head and neck cancer or bladder
           cancer was enrolled according to their FGFR expression profile (biomarker
           stratification).

        -  The study also assessed the pharmacokinetics, biomarker status, pharmacodynamic
           parameters and tumor response of BAY1163877.

        -  BAY1163877 was given twice daily as oral application. Treatment was stopped if the tumor
           continued to grow, if side effects, which the patient cannot tolerate, occurred or if
           the patient decided to exit treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  For dose escalation: Participants with any type of solid tumor (all comer) were
             eligible for dose escalation and dose expansion at MTD in Part 1; Participants
             enrolled for dose expansion (MTD expansion cohort "all comer") were stratified
             according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR
             mutation using archival or fresh tumor biopsy material

          -  For expansion cohorts: Participants were eligible for Part 2 only if they have
             histological or cytological confirmed squamous non-small cell lung cancer (sqNSCLC),
             lung adenocarcinoma, head and neck cancer or bladder cancer (BC). All participants in
             Part 2 were stratified according to high FGFR expression levels FGFR mutation using
             archival or fresh tumor biopsy specimen. BC participants with low overall FGFR
             expression levels could be included if activating FGFR3 (FGFR tyrosine kinases 3)
             mutations were confirmed

          -  Participants must have measurable disease (Response evaluation criteria in solid
             tumors (RECIST 1.1))

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2

          -  Bone marrow, liver and renal functions as assessed by adequate laboratory methods to
             be conducted within 7 days prior to starting study Treatment

          -  Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m^2 according to the modified diet
             in renal disease (MDRD) abbreviated formula

        Exclusion Criteria:

          -  Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase
             inhibitors or FGFR-specific antibodies)

          -  Concomitant therapies that cannot be discontinued or switched to a different
             medication prior to study entry that are known to increase serum phosphate levels are
             not permitted within 4 weeks prior to start of study treatment)

          -  Anticancer chemotherapy or immunotherapy during the study or within 5-halflives prior
             to start of study treatment. Mitomycin C, nitrosoureas or monoclonal antibodies with
             anticancer activity (e.g. bevacizumab or cetuximab etc.) should not be given within 6
             weeks before starting to receive study treatment or within 6 weeks of pre-treatment
             biopsy for biomarker (p-ERK1/2) studies