An open-label multi-cohort Phase 1b/2 study of derazantinib and atezolizumab in patients with urothelial cancer expressing activating molecular FGFR aberrations (FIDES-02) - Phase 1b/2 study of derazantinib and atezolizumab in patients with urothelial cancer. with urothelia

Basilea Pharmaceutica International AG0 个研究点目标入组 303 人开始时间: 2021年1月29日最近更新: 2021年4月5日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Basilea Pharmaceutica International AG
入组人数: 303

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1.ICF signed by the patient indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study, prior to any study-related procedure. 2.Male or female aged = 18 years.
•3.Histologically-confirmed transitional cell carcinoma of the urothelium of the upper or lower urinary tract (applicable to Substudies 1, 3 and 4) Note: Minor components (< 50% overall) of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change, are acceptable.
•4.Recurrent or progressing stage IV disease, or surgically unresectable, recurrent or progressing disease, as specified for each substudy:
•Substudy 1: Patients with mUC expressing specific FGFR1–3 GAs who have progressed on at least one standard chemotherapy and/or immune-checkpoint blockade and have not received prior FGFR inhibiting treatment.
•Substudy 2: Patients with any advanced solid tumor and any prior treatment (including FGFR inhibitor treatment), who have no standard treatment alternative (per multidisciplinary tumor board endorsement). •Substudy 3: First-line cisplatin-ineligible patients with patients with mUC expressing specific FGFR1–3 GAs and PD-L1 expression < 5% ('PDL1-
•low'). Cisplatin-ineligibility as defined by any one of the following criteria: 1) grade = 2 peripheral neuropathy; 2) CLCR calculated by Cockcroft-Gault >30 mL/min but < 60 mL/min; 3) hearing impairment (measured by audiometry) of > 25 dB at two contiguous test frequencies in at least one ear; 4) comorbidity that precludes high-volume hydration. Note: For
•atezolizumab, a low PD-L1 expression level is an ImmunoHistoChemistry Score of 1 using the polyclonal anti-PD-L1 rabbit antibody SP142 (Ventana, an FDA approved test), i.e., less than 5% of positive immune cells in the tumor microenvironment, which comprises tumor cells and tumor infiltrating immune cells (including macrophages, dendritic cells, and lymphocytes). •Substudy 4: Patients with FGFR inhibitor-resistant, mUC expressing specific FGFR1–3 GAs who have progressed on at least one standard regimen each of chemotherapy and immune-checkpoint blockade and have received FGFR inhibiting treatment (excluding derazantinib) Patients assessed as having progressed upon prior treatment with FGFR inhibitors must have received FGFR inhibitor treatment for at least 12 weeks and have undergone at least one on treatment tumor imaging assessment.
•Prior treatment with immune-checkpoint blockade and FGFR inhibitor in combination are not allowed; prior treatment with either sequential immune-checkpoint blockade and FGFR inhibitor treatment or combinations of FGFR inhibitor and chemotherapy are allowed. •TCS Group: Patients enrolled in the TCS Group need to have disease that is safely amenable to repeated biopsies. 5.For enrollment into the study, patients for Substudies 1, 3 and 4 require positive tumor molecular FGFR1-3 status as detailed in Appendix 1, obtained from a plasma or tissue-based assay, using standard molecular protocols approved by the local IRB/IEC, Clinical Laboratory Improvement Amendments (CLIA), or other similar agency, or, where
•applicable, US FDA-approved kits. For enrollment of patients in the EU, assays must be either fully CE-marked or CE-marked for analytical performance; tests manufactured by health institutions and used only on their own patients are exempt from the Medical Devices Regulation requirements, a

排除标准

•Prior cancer treatment
•1.Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
•One chemotherapy or biological (e.g., antibody) cycle interval•Five half-lives of any small molecule investigational or licensed medicinal product•Two weeks, for any investigational medicinal product (IMP) with an unknown half-life•Four weeks of curative radiotherapy •Seven days of palliative radiotherapy •12 months of neo-adjuvant or adjuvant chemotherapy or radiation (only applies to Substudy 3)
•2.For Substudy 3 patients, any prior treatment with anti-PD-1 or anti-PD-L1-therapeutic antibody or pathway-targeting agents; 3.For Substudy 4 patients, prior treatment with FGFR inhibitor in combination with anti-PD-1 or anti-PD-L1 therapeutic antibody or pathway-targeting agents.Critical organ impairments 4.Concurrent evidence of corneal or retinal disorder, including but not limited to bullous/band keratopathy, keratoconjunctivitis, corneal abrasion (unless related to trauma), inflammation/ulceration, confirmed by ophthalmological examination. 5.History of clinically significant cardiac disorders:
•Myocardial infarction, or New York Heart Association Class II to IV congestive heart failure, within 6 months of the first dose of study drug.•Concurrent and clinically significant abnormalities on ECG at Screening, including TcF > 450 ms for males or > 460 ms for females. 6.Serum electrolyte abnormalities defined as follows:
•Hyperphosphatemia: serum phosphate > institutional ULN
•Hyperkalemia: serum potassium > institutional ULN
•Hypokalemia: serum potassium < institutional LLN
•Hypercalcemia: corrected serum calcium > 3.1 mmol/L (> 12.5 mg/dL)
•Hypocalcemia: corrected serum calcium < 1.75 mmol/L (< 7.0 mg/dL)
•Hypomagnesemia: < 0.4 mmol/L (< 0.9 mg/dL) 7.History of major thrombotic and clinically relevant bleeding event in the last 6 months before Screening which in the assessment of the Investigator puts the patient at high risk of bleeding during the study. 8.Uncontrolled tumor-related hypercalcemia.Medical history.9.Any unresolved (at the time of Screening) clinically significant CTCAE grade 2 or greater toxicity (except for alopecia and grade 2 platinum-therapy related neuropathy, anemia grade 2 from previous anti-tumor treatment and/or medical/surgical procedures/interventions).Grade 2 renal impairment per reduced CLCR by Cockcroft-Gault of 30– 60 mL/min is generally accepted for this population (see inclusion criterion 7)10.For Substudy 1, 3 or 4 patients, known CNS metastases. Patients with CNS metastases and CNS tumors are eligible for Substudy 2.11.Lack of recovery from major (e.g., open abdominal) surgery after 4 weeks, or major elective surgery is planned during the foreseeable duration of the study.12.Concurrent uncontrolled or active infection with either human immunodeficiency virus (known HIV 1/2 antibodies positive). 13.Active hepatitis B, or hepatitis C. Active Hepatitis B is defined as a
•known positive HBsAg result. Active Hepatitis C is defined by a known positive Hep C antibody result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
•14.Active tuberculosis.15.Severe bacterial, fungal, viral and/or parasitic infections on therapeutic oral or IV medication at the time of first dose of study drug administration
•16.Significant gastrointestinal disorders that could, in the opinion of the Investigator, interfere with the a

研究者

发起方

Basilea Pharmaceutica International AG

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