320MO - Tibremciclib (BPI-16350) plus fulvestrant in patients with HR+/HER2- advanced breast cancer after progressing on endocrine therapy: A randomized, multicenter, double-blind, phase III study

Background

Tibremciclib (BPI-16350), a novel CDK4/6 inhibitor, with fulvestrant (FUL) has shown favorable tolerability and preliminary antitumor activity involving patients (pts) with HR+/HER2- advanced breast cancer (ABC) in a phase I study (ASCO 2023; NCT03791112). Here, we report the efficacy and safety of tibremciclib (TIB) with FUL in pts with HR+/HER2- locally recurrent or metastatic ABC who experienced disease progression following endocrine therapy (ET).

Methods

Eligible pts were randomly assigned (2:1) to receive TIB (400 mg, p.o, qd) or placebo (PBO) with FUL (500 mg, i.m, d1, d15, d29 and then every 28 days). The primary endpoint was investigator (INV)-assessed progression-free survival (PFS), with secondary endpoints including PFS assessed by the independent review committee (IRC), INV-assessed objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and safety.

Results

274 pts were randomized to receive TIB plus FUL (N = 184) and PBO plus FUL (N = 90). At a median follow-up of 5.55 months, the INV-assessed PFS was 11.10 months (95% CI 9.23-12.85) in the TIB group vs 5.45 months (95% CI 4.21-7.36) in the PBO group (HR 0.31 [95% CI 0.21-0.47]; p < 0.0001). Consistent benefit in risk reduction was seen for IRC-assessed PFS (HR 0.31 [95% CI 0.19-0.48]; p < 0.0001). INV-assessed ORR was 28.8% vs 6.7%, DCR was 89.1% vs 76.7%, CBR was 46.2% vs 21.1% for TIB and PBO groups, respectively. OS data were immature, with a maturity rate of 7.2%. The most common grade ≥3 treatment-emergent adverse event (TEAEs) for TIB group was neutropenia (13.0%; vs 4.4% for PBO group). TEAEs leading to discontinuation occurred in 3 pts (1.6%) in the TIB group and 0 in the PBO group. No drug-related deaths occurred in the TIB group and 1 pt (1.1%) in the PBO group.

Conclusions

The study demonstrated a significant PFS benefit for tibremciclib with fulvestrant vs placebo fulvestrant and had a good safety profile in pts with HR+/HER2- ABC after progression on ET.

Clinical trial identification

NCT05433480.

Editorial acknowledgement

Betta Pharmaceuticals Co., Ltd., Hangzhou, China.

Legal entity responsible for the study

Betta Pharmaceuticals Co., Ltd.

Funding

Betta Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.