370P - A phase Ib study to evaluate the efficacy and safety of afuresertib plus fulvestrant in subjects with locally advanced or metastatic HR+/HER2- breast cancer who failed standard of care therapies: A subgroup analysis of efficacy in PIK3CA/AKT1/PTEN-altered subjects

Background

Afuresertib is an oral, potent pan-AKT inhibitor. The phase Ib study (NCT04851613) showed that the combination of afuresertib plus fulvestrant has promising efficacy in subjects with HR+/HER2- LA/mBC who progressed on 1-2 prior lines of systemic anti-cancer therapies (with/without a CDK4/6 inhibitor). Here we report data from all enrolled subjects in the phase Ib study (N=31; cutoff date Apr 19, 2024).

Methods

Subjects received afuresertib (125 mg PO, QD) in combination with fulvestrant. Tumor FFPE slides and/or whole blood samples were obtained from the subjects. Next generation sequencing (NGS) was conducted at Predicine. Primary endpoint was investigator-assessed ORR based on RECIST 1.1.

Results

A total of 31 subjects were enrolled, among which 18 subjects (58.1%) had PIK3CA/AKT1/PTEN alteration. ESR1 mutations were detected in 9 subjects(29.0%). Median age was 54 years, 58.1% subjects were postmenopausal, 83.9% subjects had visceral metastasis. In PIK3CA/AKT1/PTEN altered and non-altered subjects, portions received prior CDK4/6 inhibitor were 72.2% and 45.5%, and received two prior endocrine therapies were 16.7% and 0%, respectively. The confirmed ORR evaluated in 28 subjects with at least one post-baseline tumor assessment was 28.6% (8/28). Confirmed ORR is 37.5% in 16 subjects with PIK3CA/AKT1/PTEN-alteration and 10% in 10 non-altered subjects, 33.3% in 9 subjects with ESR1 mutations. The mPFS was 7.5 months in overall population, 7.3 months in both PIK3CA/AKT1/PTEN-altered subgroup and ESR1 mutation subgroup. Among total 31 subjects, no SAE or TEAE >= Grade 4 were reported. No subject discontinued treatment due to TEAE.

Conclusions

Afuresertib plus fulvestrant combination demonstrated a promising antitumor activity, especially in the population with PIK3CA/AKT1/PTEN pathway alteration. The safety profile of Afuresertib plus fulvestrant was well-tolerated. This regimen warrants further investigation in phase III study.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Laekna LLC.

Funding

Laekna LLC.

Disclosure

All authors have declared no conflicts of interest.