Three cohorts will be included consisting of subjects with biliary tract cancer (Cohort 1), urothelial cancer (Cohort 2) and all other solid tumor histologies not included in Cohorts 1-2 such as NSCLC, head and neck cancer, thyroid cancer, oral cancer, breast cancer, prostate cancer and others but excluding primary brain tumors (Cohort 3).
Conditions
Interventions
Product Code: Debio 1347
Pharmaceutical Form: Film-coated tablet
CAS Number: 1265231-80-8
Current Sponsor code: Debio 1347
Other descriptive name: DEBIO 1347, Debio 1347 malate, FF284, CH5183284, C-02
Sponsors
Debiopharm International SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent given according to ICH/GCP guidelines and local regulations. 2. Cytologically or histologically confirmed advanced solid tumor. 3. Radiographic progression on prior systemic therapy; prior localized therapy (i.e., radiation, ablation, embolization) is allowed provided radiographic progression out-of-field or in the treatment field is shown. 4. Male or female =18 years of age. 5. Locally-advanced (unresectable) or metastatic disease harboring an FGFR1-3 gene fusion/rearrangement potentially leading to a functional FGFR aberrant protein, identified through local and/or central molecular assay. 6. The subject must have received at least one prior line of standard therapy appropriate for tumor type and stage of disease (if available), and, in the opinion of the Investigator, s/he would have been unlikely to tolerate or derive clinically meaningful benefit from further appropriate standard of care therapy. In particular: a. Biliary tract cancer subjects must have progressed on/after gemcitabine-based chemotherapy (including subjects who progressed within 6 months of gemtabicine-based adjuvant chemotherapy). Subjects can have received additional chemotherapy after documented intolerance to gemcitabine. b. Urothelial cancer subjects must have progressed on/after cisplatin-based or carboplatinbased chemotherapy either given for advanced disease or within 12 months from completion if given as neoadjuvant or adjuvant therapy and anti-PD1/PDL1 therapy (unless not available, contraindicated for some reasons or refused by the subject). c. NSCLC subjects must have progressed on chemotherapy and anti PD1/PDL1 therapy (unless contraindicated for some reasons). Subjects with known EGFR mutations, ALK rearrangement or BRAF V600E mutation must have received the relevant target therapy (unless not available). d. For all other tumor types, subjects must have progressed on/after appropriate SOC therapy (evidence-based level 1). Subjects who harbor genomic aberrations for which approved target therapy is available must have received such therapy. HER2+ or ER/PR+ breast cancer subjects should have received at least one line of HER2-targeted or ER-targeted, respectively. 7. Measurable disease according to RECIST criteria version 1.1. For further Inclusion Criteria please refer to the Protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. History of hypersensitivity to any of the excipients in the Debio 1347 formulation. 2. Prior treatment with a FGFR1-3 selective inhibitor. 3. History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes, lung nodules and asymptomatic vascular or cartilage/tendon calcifications. 4. Current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic examination. 5. Chemotherapy, radiotherapy or small molecule anti-cancer agents within 2 weeks prior to initial dosing with Debio 1347 (3 weeks for immune checkpoint inhibitors). 6. Administration of any investigational agent within 2 weeks prior to initial dosing with Debio 1347 (3 weeks for immune checkpoint inhibitors). 7. Surgery requiring general anesthesia, except diagnostic biopsy or local procedure, within 3 weeks prior to initial dosing with Debio 1347 and/or if the subject has not fully recovered from the surgery. 8. Grade > 1 NCI-CTCAE v5.0 AEs or toxicities from previous treatments except: a. Albumin (= 2.5 g/dL is allowed). b. AST and ALT in subjects with liver metastases. c. ALP in subjects with bone metastases . d. Any grade of alopecia is allowed. e. Other Grade 1-2 clinically insignificant laboratory abnormalities are allowed. For further Exclusion Criteria please refer to the Protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of Debio 1347 in terms of ORR in subjects with solid tumors harboring FGFR1-3 gene fusion/rearrangement.;Secondary Objective: 1. To evaluate the efficacy of Debio 1347 in terms of DoR, DCR, PFS and OS. 2. To assess the safety of Debio 1347. 3. To assess exposure-response relationships vs efficacy and safety (notably QTcF).;Primary end point(s): ORR (defined as the proportion of subjects with a BOR of partial or complete response) as centrally measured by RECIST 1.1 criteria.;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. DoR (defined as the time from the date of the initial partial or complete response to date of the first documented progression or death due to any cause). 2. DCR (defined as the proportion of subjects with a BOR of CR or PR or SD). 3. PFS (defined as the time from the start date of treatment to date of the first documented progression or death due to any cause). 4. OS (defined as the time from the start date of treatment to date of death due to any cause). 5. Proportion of subjects with TEAEs assessed by NCI-CTCAE v5.0 and SAEs. 6. Debio 1347 plasma exposure (Ctrough, AUC? and any other PK parameters as deemed appropriate) and relationships with efficacy and safety endpoints; Debio 1347 plasma concentration (C)-QTcF relationship based on ECG and PK matching time-points.;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Australia, Austria, Brazil, Bulgaria, Canada, Croatia, Czech Republic, Denmark, Finland, France, Germany, Greece, Korea, Republic of, Mexico, Netherlands, Norway, Philippines, Poland, Romania, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical department
Debiopharm International SA
Outcome results
None listed