Abstract
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
Annals of oncology, Vol.35(Supplement 2), pp.S373-S374
09/2024
DOI: 10.1016/j.annonc.2024.08.318
Abstract
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.
Details
- Title: Subtitle
- 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
- Creators
- P. Zhang - Cancer Hospital of Chinese Academy of Medical SciencesB. Xu - Cancer Hospital of Chinese Academy of Medical SciencesT. Sun - Liaoning Cancer Hospital & InstituteY. Wang - Sun Yat-sen Memorial HospitalW. Li - First Hospital of Jilin UniversityZ. Tong - Tianjin Medical University Cancer Institute and HospitalS. Phadke - University of IowaT.M. Feinstein - Piedmont Cancer InstituteJ. Qu - Clinical Development Dept., Laekna LLC., New Jersey, NJ, USAP. Guo - Clinical Development Dept., Laekna LLC., New Jersey, NJ, USAW. Ma - Clinical Development Dept., Laekna LLC., New Jersey, NJ, USAM. Zhang - Clinical Development Dept., Laekna LLC., New Jersey, NJ, USAY. Yue - Clinical Development Dept., Laekna LLC., New Jersey, NJ, USA
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.35(Supplement 2), pp.S373-S374
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.annonc.2024.08.318
- ISSN
- 0923-7534
- Language
- English
- Date published
- 09/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984708955202771
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