Abstract 78P
Background
TT-00434 is an irreversible, highly selective inhibitor of FGFR1, 2, and 3 with potent preclinical activity against tumors harboring FGFR aberrations. We present initial results from the first-in-human phase 1 study of TT-00434 orally administrated in patients (pts) with solid tumors.
Methods
This phase 1, multicenter, open-label, dose-escalation study enrolled pts with advanced solid tumors who had exhausted all available standard treatments. An accelerated titration design followed by a standard 3 + 3 scheme was used. Pts received a single daily dose of TT-00434 continuously for 28-day cycles. Key objectives included determining the recommended phase 2 dose (RP2D), safety, PK, pharmacodynamics (PD) and preliminary antitumor activity.
Results
As of 7 Aug 2023, 11 eligible pts received TT-00434 40 mg (n = 1), 80 mg (n = 6), and 160 mg (n = 4). One pt in 160 mg experienced Grade (G) 2 fatigue, vomiting and dizziness, resulting in dose interruption for 13 days (≥7 days) in Cycle 1 which was qualified as DLTs. The most frequently reported treatment-related adverse events included hyperphosphatemia (91%), fatigue (45%), hypercalcemia (36%), dry mouth (36%) and decreased appetite (36%). Two G3 events of fatigue and hyponatremia (each n=1) were observed. No G4 or G5 AEs were reported. The exposure (AUC and Cmax) was dose proportional from 80 to 160 mg. The maximum serum phosphate concentration as PD biomarker reached plateau (6.1∼8.9 mg/mL) at 80 mg. Stable diseases were observed in 2 pts with bladder cancer and endometrial cancer. One cholangiocarcinoma pt with FGFR alteration (FGFR2(17)-ARHGAP24(3) fusion) treated at 80 mg achieved partial response. The treatment lasts 203+ days and is still ongoing. Based on safety, efficacy and PK/PD assessments, the RP2D was determined as 80 mg QD.
Conclusions
This first-in-human study of TT-00434 showed a manageable and well-tolerated safety profile. The preliminary antitumor activity was observed in pt with FGFR2 altered cholangiocarcinoma. Further evaluation of the efficacy and safety of TT-00434 in solid tumors with FGFR1-3 alterations is encouraged.
Clinical trial identification
NCT04830501.
Editorial acknowledgement
Legal entity responsible for the study
TransThera Sciences (Nanjing), Inc.
Funding
TransThera Sciences (Nanjing), Inc.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
426P - Characterization of a novel comprehensive genomic profiling test with better detection of heterozygous deletions and gene fusions
Presenter: ryouta kakuta
Session: Poster Display
Resources:
Abstract
427P - Real-world performance of a comprehensive next-generation sequencing (NGS) panel for patients (pts) with solid tumors from Asia and the Middle East (AME)
Presenter: Nitesh Rohatgi
Session: Poster Display
Resources:
Abstract
428P - What do women want to see in a personalized breast cancer risk report? A qualitative study of Asian women of two countries
Presenter: Faustina Audrey Agatha
Session: Poster Display
Resources:
Abstract
429P - Clinical utility and outcomes of liquid biopsy-based next generation sequencing in identification of actionable genomic mutations in solid malignancy: A single center retrospective study in the Philippines
Presenter: Omar Maaño
Session: Poster Display
Resources:
Abstract
436P - Chemotherapy-induced hand-foot syndrome, comparative efficacy and safety of pharmacological prophylaxis: Systematic review and network meta-analysis
Presenter: Anand Srinivasan
Session: Poster Display
Resources:
Abstract
437P - A randomized single blinded phase II trial comparing efficacy and quality of life of topical aloe vera gel plus urea cream versus urea cream alone for prevention of hand-foot syndrome in cancer patients receiving capecitabine
Presenter: Lucksika Wanichtanom
Session: Poster Display
Resources:
Abstract
438P - A novel treatment for immune checkpoint inhibitor-related myocarditis
Presenter: Takahiro Niimura
Session: Poster Display
Resources:
Abstract
439P - Randomized controlled trial evaluating efficacy of topical urea-based cream for capecitabine-associated hand-foot syndrome prevention
Presenter: Concord Wongkraisri
Session: Poster Display
Resources:
Abstract
440P - Real-world adverse events of targeted therapy reported by pharmacist in oncology clinic
Presenter: TIKUMPORN PORNWISETSIRIKUL
Session: Poster Display
Resources:
Abstract
441P - The prophylactic efficacy of telpegfilgrastim, a Y-shape branched pegylated G-CSF in patient with chemotherapy-induced neutropenia: A multicenter, randomized phase III study
Presenter: Xinshuai Wang
Session: Poster Display
Resources:
Abstract