Phase 1b/2 study of rogaratinib (BAY 1163877) in combination with atezolizumab in urothelial carcinoma

Phase 1

Conditions: FGFR-positive locally advanced or metastatic urothelial carcinoma
MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-001483-38-AT

Lead Sponsor: Bayer AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 210

Inclusion Criteria

Part A:
•Male/female patients =18 years of age (at least age of legal maturity)
•Urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:
oHistologically confirmed.
oPatients with mixed histology required to have dominant transitional cell pattern
oLocally advanced (T4, any N; or any T, N2-3) or metastatic disease (any T, any N +M1)
Note:Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (N2-3)
•High FGFR1 or 3 mRNA expression levels (RNAscope score of 3+ or 4+; measurement is part of this protocol) in archival or fresh tumor biopsy specimen
•Measurable disease according to RECIST v1.1
•ECOG PS 0 or 1
•Adequate hematological and end organ function
•Recovery to NCI CTCAE v.4.03 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure-related toxicity (patients with persistent alopecia, anemia [hemoglobin = 9 g/dl], any grade peripheral neuropathy, impaired renal function (GFR>30ml/min/1.73m2), hearing loss and/or hypothyroidism that is adequately controlled by hormone replacement can be included
•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 + the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. Prior local intra-vesical chemotherapy/local immunotherapy allowed if completed at least 4 weeks before first study drug admin. Regionally available standard of care options must be considered for all patients
•Ineligibility for cisplatin-based chemotherapy
•Negative serum pregnancy test in women of childbearing potential (performed within 7 days before the first treatment). Negative results must be available before the first study drug administration
•WOCBP+fertile men must agree to use adequate contraception when sexually active from signing of ICF for study treatment eligibility until at least 5 months after last study atezolizumab administration or until at least one week after the last rogaratinib intake, whichever is later. Investigator or designated associate is requested to advise patient how to achieve highly effective birth control. Highly effective (failure rate of less than 1% per year) contraception methods include:
•Combined (estrogen+progesterone containing: oral, intravaginal, transdermal) +progesterone-only (oral, injectable, implantable) hormonal contraception associated with inhibition of ovulation
•IUD/IUS
•Bilateral tubal occlusion/vasectomized partner
•Sexual abstinence
oPeriodic abstinence + withdrawal are not acceptable methods of contraception.
Male patients with female partner of childbearing potential must use condom+ ensure that an additional form of contraception is also used during treatment and until 5 months after last atezolizumab administration or until at least one week after the last rogaratinib intake, whichever is later.
Part B:
•Male/female patients =18 years of age (at least age of legal maturity)
•Urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra, meeting all of the following criteria:
oHistologically confirmed
oPatients with mixed hi

Exclusion Criteria

Part A:
• Inability to swallow oral medications
• Any malabsorption condition
• Current diagnosis of retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), central serous retinopathy or retinal vein occlusion
• Previous or concurrent cancer except
o cervical carcinoma in situ
o treated basal-cell carcinoma or squamous cell skin cancer
o localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score = 6 and PSA < 10 ng/mL undergoing active surveillance and treatment-naïve)
o any other cancer curatively treated > 3 years before the first study drug administration
• Investigational drug treatment outside of this study during or within 4 weeks before the first study drug administration
• Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies)
• Previous assignment to treatment during this study
• Severe (CTCAE v.4.03 Grade 3) infections within 4 weeks before the first study drug administration, including but not limited to hospitalization for complication of infection, bacteremia, or severe pneumonia
• History of autoimmune disease except: a) autoimmune-related hypothyroidism clinically stable on thyroid replacement hormone; b) controlled Type-I diabetes mellitus on a stable dose of insulin regimen
• History or current condition of uncontrolled cardiovascular disease
• Systolic/diastolic blood pressure = 100/60 mmHg and heart rate = 100/min
• Renal failure requiring peritoneal dialysis or hemodialysis
• 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 and that cannot be discontinued or switched to a different medication before start of study treatment
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage / bleeding event CTCAE v.4.03 = Grade 3 within 4 weeks before the first study drug administration

Part B:
• Inability to swallow oral medications
• Any malabsorption condition
• Current diagnosis of retinal disorders including retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
• Previous or concurrent cancer except
o cervical carcinoma in situ
o treated basal-cell carcinoma or squamous cell skin cancer
o localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (T1/T2a, Gleason score = 6, and PSA = 10 ng/mL undergoing active surveillance and treatment-naïve
o any other cancer curatively treated > 3 years before randomization
• Ongoing or previous anti-cancer treatment within 4 weeks before randomization
• Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies)
• Previous assignment to treatment during this study
• Severe (CTCAE v.4.03 Grade 3) infections within 4 weeks before randomization, including but not limited to hospitalization for complication of infection, bacteremia, or severe pneumonia
• History of autoimmune disease except: a) autoimmune-related hypothyroidism clinically stable on thyroid replaceme

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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