Advanced solid tumors MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: TAS-120
Product Code: TAS-120
Pharmaceutical Form: Tablet
INN or Proposed INN: Not yet assigned
CAS Number: 1448169-71-8
Sponsors
Taiho Oncology Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent. 2. Is = 18 years 3. Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting the following criteria: a. Phase 1 Expansion i. Patient has failed all standard therapies or standard therapy does not exist or is not tolerated. ii. Patient is eligible for 1 of the following enrollment groups, based on diagnosis, prior therapy, and FGF/FGFR aberrations as shown: Group 1 (Enrollment Suspended as of Amendment 7): Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions. Group 2: Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions, and has not received or received less than 1 cycle of prior chemotherapy (due to intolerance or patient refusal). Group 3 (Enrollment Suspended as of Amendment 7): Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions and has received prior treatment with FGFR inhibitors. Group 4 (Enrollment suspended as of Amendment 7): Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR abnormalities other than FGFR2 gene fusions Group 5: Patient has a primary CNS tumor harboring FGFR gene fusion or FGFR1 activating mutation and fulfills the criteria (i and ii). Group 6 (Enrollment Suspended as of Amendment 7): Patient has advanced urothelial carcinoma harboring FGFR3 fusions or FGFR3 activating mutations. Group 7: Patient has any tumor type not included in one of the prior groups, harboring FGFR2 amplification (no minimum number of copies). Group 8 (Enrollment Suspended as of Amendment 7): Patient has any tumor type not included in one of the prior groups, harboring FGFR gene fusions or activating mutations. b. Phase 2 i. Patient has histologically or cytologically confirmed, locally advanced, metastatic, unresectable iCCA harboring FGFR2 gene fusions or other FGFR2 rearrangements based on results from either of the following a. Testing by Foundation Medicine: i. As part of study pre-screening; or ii. Previously tested by Foundation Medicine; in this case, it is requested that tumor tissue should be provided to Foundation Medicine if available. b. Local laboratory testing using next generation sequencing [NGS], fluorescence in situ hybridization [FISH], or other assays that can determine FGFR2 gene fusions or other FGFR2 rearrangements on tumor tissues or from ctDNA; it is requested that patients enrolled on this basis provide tumor tissues to Foundation Medicine if available from either archival samples or fresh tumor biopsy. ii. Patient has been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy. Patients with prior adjuvant gemcitabine-platinum chemotherapy are eligible if the patient had recurrence within 6 months of the last dose of the regimen. iii. Patient has documentation of radiographic disease progression on the most recent prior therapy 4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO criteria (2010) for brain tu
Exclusion criteria
Exclusion criteria: 1. History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis. 2. History and/or current evidence of clinically significant ectopic mineralization/calcification. 3. History and/or current evidence of clinically significant retinal disorder confirmed by retinal examination. 4. History or current evidence of serious uncontrolled ventricular arrhythmias 5. Fridericia’s corrected QT interval (QTcF) > 470 ms on ECG conducted during Screening. 6. Treatment with any of the following within the specified time frame prior to the first dose of TAS-120: a. Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of TAS 120). b. Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks. c. Patients with locoregional therapy, e.g., transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks. d. Any noninvestigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to TAS 120 administration (mitomycin within prior 5 weeks). • Targeted therapy or immunotherapy within 3 weeks or within 5 half-lives (whichever is shorter) e. Any investigational agent received within 5 half-lives of the drug or 4 weeks, whichever is shorter. Concurrent participation in an observational study may be allowed after review by the Sponsor’s Medical Monitor. f. Patients with prior FGFR-directed therapy. 7. A serious illness or medical condition(s) including, but not limited to, the following: a. Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for = 1 month. b. Known acute systemic infection. c. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV (see Appendix D, New York Heart Association [NYHA] Classification) within the previous 2 months; if > 2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms. d. Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the investigator. e. Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death. f. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the investigator would make the patient inappropriate for entry into this study. 8. Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention (except for gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LH-RH) agonists in prostate cancer or adjuvant hormonal therapy in breast cancer). 9. Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The endpoint is based on Overall response rate (ORR). ; Main Objective: Phase 1 Dose Escalation: completed Phase 1 Expansion •To evaluate ORR in cholangiocarcinoma patients with tumors harboring FGFR2 gene fusions or other FGFR abnormalities • To evaluate ORR and EPR (defined as progression-free rate at the end of Cycle 2) in patients with primary CNS tumors harboring FGFR gene fusions or FGFR1 activating mutations • To evaluate ORR in a basket of tumor types with tumors harboring FGFR2 amplifications •To evaluate ORR in a basket of tumor types with tumors harboring any FGFR gene fusions or activating mutations Phase 2: • To confirm ORR in iCCA patients with FGFR2 gene fusions or other FGFR2 rearrangements based on independent central radiology review. ; Secondary Objective: Phase 1 Dose Escalation: completed Phase 1 Expansion •To investigate the safety of TAS-120. •To evaluate disease control rate (DCR), DOR, PFS and OS in each treatment group. Phase 2: Key secondary •To evaluate DOR Other secondary •To evaluate the safety and tolerability of TAS-120 •To evaluate DCR, PFS, and OS •To evaluate Patient-Reported Outcomes (PROs) ; Primary end point(s): For Phase 1 Expansion, the primary endpoint is ORR in each treatment group (and EPR for primary CNS tumors). For Phase 2, the primary endpoint is ORR. Primary endpoints will be based on the independent review of images by the Core Imaging Laboratory. In addition, for the Phase 2 part of the study, sensitivity analyses for some key efficacy endpoints (e.g., ORR, and PFS) will be performed based on investigato | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For Phase 1 Expansion, secondary endpoints of DOR, DCR, PFS, and OS in each treatment group. For Phase 2, secondary endpoints of DOR, DCR, PFS, PROs and OS. Primary endpoints will be based on the independent review of images by the Core Imaging Laboratory. In addition, for the Phase 2 part of the study, sensitivity analyses for some key efficacy endpoints (e.g., ORR, and PFS) will be performed based on investigators or local radiologist assessments. ; Timepoint(s) of evaluation of this end point: The assessment of DCR will parallel that of ORR, with DCR defined as the proportion of patients with objective evidence of CR, PR, or SD, except that there is no requirement for a confirmation of an SD response, if it is maintained for at least 6 weeks post treatment initiation. Disease control rate will be analyzed using the same methodology as ORR. | — |
Countries
Australia, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactHead of Clinical Development
Taiho Oncology, Inc
Outcome results
None listed