Follicular lymphoma (FL) poses a significant challenge due to its relapsing nature and limited treatment options, particularly for patients with early progression or refractory disease. According to DelveInsight estimates, approximately 37,000 cases of follicular lymphoma were reported in the US in 2023. TQ-B3525, a novel oral PI3K α/δ inhibitor developed in China, offers a potential solution to this dilemma. By targeting both PI3K catalytic subunits α and δ, TQ-B3525 addresses drug resistance issues and minimizes toxic side effects, presenting a valuable therapeutic option.

Early Phase I trial results demonstrate TQ-B3525's remarkable efficacy in refractory/relapsed FL patients. This promising data suggests TQ-B3525 could play a crucial role in improving objective response rates, extending survival, and enhancing quality of life for patients facing successive relapses. As efforts continue to combat the challenges posed by R/R FL, TQ-B3525 stands out as a beacon of hope in the quest for better treatment outcomes. The results presented at ASCO 2024 were as follows:

Efficacy outcomes 

Based on results (ORR, 88.0%; DOR, 11.8 months; PFS, 12.0 months) in 25 patients at stage 1, a second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received a median of 3 prior lines, with 56.1% refractory to previous therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6%, with 28 complete responses. Seven had stable disease for DCR of 95.1%. Median TTR was 1.8 months. Among 71 responders, the median DOR was not reached; the 18-month DOR rate was 51.6%. At a median follow-up of 13.3 months, median PFS was 18.5 months; the estimated 24-month OS rate was 86.1%. Response rates and survival data were consistent across all subgroups.

Safety result: 

• TQ-B3525 showed favorable efficacy and safety for relapsed/refractory follicular lymphoma patients after ≥2 lines prior therapies.

• Grade 3 or higher treatment-related adverse events were observed, with neutropenia (22.0%), hyperglycemia, and diarrhea being common

KOL insights

“TQ-B3525 is well-tolerated in Chinese patients with advanced malignancies, and demonstrated high promising antitumor activity in R/R lymphoma patients.” –PhD, Department of Hematology, China.

“TQ-B3525 has shown preliminary promising clinical activities and favorable in advanced malignancies, especially R/R lymphoma.” – PhD, Department of Oncology, China.

Conclusion- 

Novel oral PI3K α/δ inhibitor TQ-B3525 has shown remarkable efficacy and safety in preclinical and Phase I studies. With lower inhibitory concentrations than idelalisib and duvelisib, and similar to copanlisib, TQ-B3525 is a potent therapeutic candidate. Early Phase I trial results demonstrate outstanding efficacy in refractory/relapsed follicular lymphoma patients. Recent data presented at ASCO further confirm its favorable efficacy and manageable safety profiles, bolstering its potential as a valuable treatment option for heavily pretreated Chinese patients with relapsed/refractory follicular lymphoma.