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
529P - Ramucirumab plus docetaxel after combination chemoimmunotherapy in patients with non-small cell lung cancer: A prospective observational study
Presenter: Tadaaki Yamada
Session: Poster Display
Resources:
Abstract
530P - MYC recruits tumor-associated macrophage to sustain metastatic malignancy of lung adenocarcinoma micropapillary subtype through epigenetic reprogramming
Presenter: Xuming Song
Session: Poster Display
Resources:
Abstract
531P - Effect of combinational targeted therapy for AXL and ATR against malignant mesothelioma cells
Presenter: Soichi Hirai
Session: Poster Display
Resources:
Abstract
532P - The changes of the serum SMRP levels is useful to predict the antitumor efficacy of ipilimumab plus nivolumab combination therapy in patients with malignant pleural mesothelioma
Presenter: Taiichiro Otsuki
Session: Poster Display
Resources:
Abstract
533P - Efficacy in the elderly NSCLC patients in SCORPION study: Phase II study of DTX plus RAM following platinum-based chemotherapy plus ICIs
Presenter: Teppei Yamaguchi
Session: Poster Display
Resources:
Abstract
534P - DSC2 promotes the proliferation, metastasis and drug resistance of lung cancer by activating the PI3K/AKT pathway
Presenter: Qi Li
Session: Poster Display
Resources:
Abstract
535P - Alteration in NKX2-1 CN reshapes the oncogenic, immunologic, and prognostic landscapes in NSCLC
Presenter: Herdee Gloriane Luna
Session: Poster Display
Resources:
Abstract
536P - The evaluation and long-term outcome of pulmonary metastasectomy for osteosarcoma: A 20-year experience of Shanghai Rujin Hospital
Presenter: Zhusheng Zhang
Session: Poster Display
Resources:
Abstract
537P - The impact of treatment-free interval on patient outcome after pulmonary metastasectomy for sarcoma
Presenter: Po-Kuei Hsu
Session: Poster Display
Resources:
Abstract
538P - First-line chemoimmunotherapy for metastatic thymic carcinoma
Presenter: Victoria Andreas
Session: Poster Display
Resources:
Abstract