Abstract
ACTR-52. PHASE 1 STUDY OF FT-2102, AN INHIBITOR OF MUTANT IDH1, IN PATIENTS WITH RELAPSED/REFRACTORY IDH1 MUTANT GLIOMAS: PRELIMINARY SAFETY AND CLINICAL ACTIVITY
Neuro-oncology (Charlottesville, Va.), Vol.21(Supplement_6), pp.vi25-vi25
11/11/2019
DOI: 10.1093/neuonc/noz175.094
PMCID: PMC6847867
Abstract
Abstract
BACKGROUND
Isocitrate dehydrogenase mutations (mIDH1) are present in > 70% of patients with Grade II/III gliomas resulting in production and accumulation of (R)-2-hydroxyglutarate causing DNA hypermethylation and promoting tumorigenesis. FT-2102 is a potent, brain penetrant (Kpuu=0.4 in intact rodent) and selective inhibitor of mIDH1.
METHODS
Patients with advanced relapsed/refractory mIDH1 gliomas received FT-2102 150mg BID, orally. Following a dose confirmation 3 + 3 Phase 1b, 20 pts enrolled in a Simon 2 stage Phase 2 study (NCT: 03684811).
RESULTS
As of 01-May-2019, 23 with glioma (Grade at enrollment: II/III/IV; n=4, n=12 & n=7 respectively) were treated with FT-2102 monotherapy. The patient’s median age was 46 years (range: 23–64) & 61% were male. Median number of prior treatments was 2 (range 1–5) and 78% had received prior temozolomide. mIDH1 status was locally determined (IHC, NGS or PCR): R132H, R132L, R132C & unspecified (n=15, n=2, n=1 & n=5). Median duration of FT-2102 treatment to date was 40 days (range: 26–177), with 1 patient discontinuing (disease progression). Treatment emergent adverse events (all grades, regardless of attribution) that occurred in >10% of were: fatigue (22%), nausea (17%), diarrhea (17%), ALT increase (13%), headache (13%) and AST increase (13%), none leading to treatment discontinuation. None experienced an adverse event of QTcF prolongation or skin hyperpigmentation. There were no protocol-defined DLT’s. To date, six had at least 1 evaluable post-baseline response assessment, with best response of 1 PR (unconfirmed as of data cutoff), 3 SD and 2 PD. Responses of patients remaining on FT-2102 will be updated as available. Evaluations of serum/CSF pharmacokinetics and selected pharmacodynamics will be provided.
CONCLUSION
FT-2102 at 150 mg BID demonstrates acceptable safety and tolerability with potential clinical activity in with gliomas. The Phase 2 study is ongoing, evaluating both single agent, FT-2102 and in combination with azacitidine.
Details
- Title: Subtitle
- ACTR-52. PHASE 1 STUDY OF FT-2102, AN INHIBITOR OF MUTANT IDH1, IN PATIENTS WITH RELAPSED/REFRACTORY IDH1 MUTANT GLIOMAS: PRELIMINARY SAFETY AND CLINICAL ACTIVITY
- Creators
- Macarena I De la Fuente - University of MiamiHoward Colman - Huntsman Cancer InstituteMark Rosenthal - Peter MacCallum Cancer CentreBrian A Van Tine - Washington University in St. LouisEkokobe Fonkem - Baylor Scott & White HealthTobias Walbert - Henry Ford Health SystemMohammed Milhem - University of IowaKate Lipford - Forma TherapeuticsSanjeev Forsyth - Forma TherapeuticsSylvie Guichard - Forma TherapeuticsJulie Brevard - Forma TherapeuticsYelena Mikhailov - Forma TherapeuticsBlythe Thomson - Forma TherapeuticsVarun Monga - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Neuro-oncology (Charlottesville, Va.), Vol.21(Supplement_6), pp.vi25-vi25
- DOI
- 10.1093/neuonc/noz175.094
- PMCID
- PMC6847867
- ISSN
- 1522-8517
- eISSN
- 1523-5866
- Language
- English
- Date published
- 11/11/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363309302771
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