Abstract 286P
Background
Isocitrate dehydrogenase 1 inhibitors (IDH1i) have a proven role for the management of IDH1 altered cholangiocarcinoma (CCA) subsequent to chemotherapy. However, there is an urgent necessity for the development of novel inhibitors due to their limited efficacy. TQB3454 has been identified as a potent and innovative IDH1i effectively targeting various mutations in the IDH1 kinase domain.
Methods
TQB3454 was escalated in a 3+3 design from 100 mg to 900 mg once daily (QD) in 28-day cycles in pretreated patients with advanced malignancies. Response (RECIST 1.1) was assessed every 8 weeks. Patients in CCA cohort had recurrence of progressive mIDH1 CCA following standard therapy. Pooled analyses of treatment-related adverse events (TRAEs), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median over survival (OS) and in the stratified CCA population were performed.
Results
A total of 36 advanced CCA pts were enrolled between August 2020 and March 2023. The median age of patients in this cohort is 60 years (range:30-78), with 60% being female. All patients have completed first-line chemotherapy, and 47.2% have progressed from second-line treatment. Additionally, 63.7% of the patients received immunotherapy involving immune checkpoint inhibitors, 63.9% were treated with TKI drugs, and 38.9% underwent interventional treatment before enrollment. As of February 20, 2024, there were no dose-limiting toxicities. TRAEs were reported in 30 (83.3%) pts, with G3 in 10 (27.8%) and no G4-5. The most prevalent TRAEs (>15%) encompass reductions in white blood cell count 33.3%, G3 2.8%, platelet count (22.2%, G3 2.8%）, proteinuria (16.7%, G3 0%）and anemia (16.7%, G3 5.6%). Among 33 evaluable pts, the ORR was 9.1% (95%CI, 1.9-24.3), while the DCR reached 66.7% (95%CI, 48.2-82.0). The median PFS was 4.7 months (95%CI, 1.0-8.0), and the median OS was 16.1 months (95%CI, 10.1-22.1).
Conclusions
These results suggest that TQB3454 has a manageable toxicity profile and notable clinical benefit in CCA pts with mutant IDH1. A phase III clinical trial aimed to further evaluate the efficacy and safety of TQB3454 for CCA with IDH1 mutations is currently underway.
Clinical trial identification
NCT04481607.
Legal entity responsible for the study
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Funding
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.