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Updated: Jun 22, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Preclinical evaluation and phase 1 study of the PI3Kα/δ inhibitor TQ-B3525 in Chinese patients with advanced cancers
Zhiming Li1, Xiang Li2,3,4, Su Li5
1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Background:
Phosphatidylinositol 3-kinase (PI3K) inhibitors transformed management of various malignancies. This study preclinically characterized TQ-B3525 (dual PI3Kα/δ inhibitor) and assessed the recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics in relapsed or refractory (R/R) lymphoma or advanced solid tumors (STs).
Methods:
Oral TQ-B3525 was given at eight dose levels on a 28-day cycle. Primary end points were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and safety.
Results:
TQ-B3525 showed high selectivity and suppressed tumor growth. Between June 12, 2018, and November 18, 2020, 80 patients were enrolled (63 in dose-escalation cohort; 17 in dose-expansion cohort). Two DLTs occurred in two (two of 63, 3.2%) DLT-evaluable patients; MTD was not identified. TQ-B3525 at 20 mg once daily was selected as RP2D. Grade 3 or worse treatment-related adverse events mainly included hyperglycemia (16.3%), neutrophil count decreased (15.0%), and diarrhea (10.0%). Two (2.5%) treatment-related deaths were reported. Sixty patients with R/R lymphoma and 11 advanced STs demonstrated objective response rates of 68.3% and 9.1%, disease control rates of 91.7% and 54.6%, median progression-free survivals of 12.1 and 1.1 months; median overall survivals were not reached.
Conclusion:
TQ-B3525 exhibited rapid absorption and a nearly proportional increase in exposure. Acceptable safety and promising efficacy support further investigation of TQ-B3525 (20 mg once daily) for R/R lymphoma.
Insights
TQ-B3525, a dual PI3Kα/δ inhibitor, demonstrated promising efficacy and acceptable safety in patients with relapsed or refractory lymphoma. Further investigation of TQ-B3525 at 20 mg daily is warranted for this patient population.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Phosphatidylinositol 3-kinase (PI3K) inhibitors are crucial in treating various cancers.
- TQ-B3525 is a novel dual PI3Kα/δ inhibitor with preclinical characterization.
Purpose of the Study:
- To assess the recommended phase 2 dose (RP2D), safety, and efficacy of TQ-B3525.
- To evaluate pharmacokinetics in patients with relapsed or refractory (R/R) lymphoma or advanced solid tumors (STs).
Main Methods:
- Oral TQ-B3525 was administered at eight dose levels in a 28-day cycle.
- Primary endpoints included dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and safety assessments.
- Patients with R/R lymphoma and advanced STs were enrolled in dose-escalation and dose-expansion cohorts.
Main Results:
- TQ-B3525 demonstrated high selectivity and tumor growth suppression.
- The recommended phase 2 dose (RP2D) was determined to be 20 mg once daily.
- Objective response rates were 68.3% for R/R lymphoma and 9.1% for advanced STs, with manageable treatment-related adverse events.
Conclusions:
- TQ-B3525 showed rapid absorption and dose-proportional exposure.
- The drug exhibited acceptable safety and promising efficacy in R/R lymphoma.
- Further clinical investigation of TQ-B3525 at 20 mg once daily is supported for R/R lymphoma.
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