393P - A phase II study to evaluate the efficacy and safety of TSL-1502 capsules in breast cancer patients with germline BRCA mutations

Background

TSL-1502 is a novel PARP inhibitor and has shown potential efficacy and good safety profile in preclinical studies and phase I clinical study. This phase II study was to evaluate the efficacy and safety of TSL-1502 capsules in breast cancer, and to determine the optimized dosage for further development.

Methods

This was a randomized, open-label, active controlled, multi-center study. Adult patients with HER2 negative locally advanced or metastatic breast cancer harboring germline BRCA 1/2 mutations were randomized (2:2:1) to receive TSL-1502 350mg QD, TSL-1502 500mg QD or chemotherapy by investigator’s choice (eribulin, capecitabine or vinorelbine). Eligible patients should had received ≤3 lines of chemotherapy for metastatic disease and were resistant to endocrine therapy if they had positive HR. The primary endpoint was ORR by IRC.

Results

As of April 2024, 52 subjects were randomized and had completed the 24W ORR evaluation. Of the 51 patients who were treated, 22 subjects received TSL-1502 350mg, 20 subjects received TSL-1502 500mg, and 9 subjects received chemo. 24 (47.06%) subjects had triple negative breast cancer, while 27 (52.94%) subjects had positive HR. 34 (66.67%) subjects received ≤1 line of chemo at metastatic stage. The ORR among subjects who have measurable target lesions was 40.00% (8/20, 95%CI: 19.12-63.95%) for TSL-1502 350mg, 57.89% (11/19, 95%CI: 33.50-79.75%) for TSL-1502 500mg, and 50.00% (4/8, 95%CI: 15.70-84.30%) for chemo, respectively. The median PFS was 5.75m, 12.48m and 9.17m respectively. The median OS was not reached. For the patients who had received ≤1 line of chemo, TSL-1502 500mg group achieved an ORR of 83.33% (10/12, 95%CI: 51.59-97.91%), and median PFS was 12.48m. No drug-related death was observed. TSL-1502 related AEs with CTCAE Grade ≥ 3 included anemia 38.10% (16/42), neutrophil count decrease 28.57% (12/42), white blood cell decreased 23.81% (10/42) and platelet count decreased 14.29% (6/42).

Conclusions

TSL-1502 350mg and 500mg both showed preliminary anti-cancer activity in HER2 negative gBRCA 1/2 mutant breast cancer, while the higher dose showed potential better efficacy. Both dosages were well tolerated. The dose of 500mg is going to be developed for further studies.

Clinical trial identification

NCT05420779, Release date: June 15, 2022.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Jiangsu Tasly Diyi Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.