Abstract CT128: Phase I/II clinical trials of LAE005, afuresertib plus nab-paclitaxel in patients with advanced solid tumors, primarily in patients with triple-negative breast cancer (TNBC)
Authors: Xu Binghe , Zhang Pin , Wang Ying , Tong Zhongsheng , Yao Tingjing , Wang Xian , Wang Zijia , Guo Pengfei , Ma Wenyue , YUE Yong 
Published: April 2024

Abstract
Background: AKT inhibitor was reported to be a potential treatment for drug-resistant tumors by reducing AKT activity, and a synergistic agent of ICIs. Afuresertib is an oral pan-AKT inhibitor that has shown clinical efficacy in multiple tumors. The phase I part of this study assessed the safety, tolerability, and anti-tumor activity of the combination therapy of LAE005 (PD-L1 antibody) plus afuresertib plus nab-paclitaxel in advanced solid tumors, primarily in TNBC.
Methods: This is a multi-center, open-label, dose-escalation and proof-of-concept phase I/II study (NCT05390710). In phase I part, patients with advanced solid tumors (TNBC preferred) who have failed 0 to 3 lines of standard treatment are eligible. ECOG score 0-1. Efficacy evaluation is based on RECIST 1.1. Dose escalation uses Bayesian optimal interval (BOIN) design.
Results: As of December 11, 2023, 22 subjects were enrolled and dosed. The median prior line of systematic anti-tumor therapy was 1 (0-3), including chemotherapy, PAPR inhibitor or ICIs. Six subjects (3 TNBC, 2 HR+ BC, 1 lung adenocarcinoma) were enrolled in cohort 1 (afuresertib 100 mg PO QD + LAE005 1200 mg IV Q3W + nab-paclitaxel 125 mg/m2 IV D1, D8, Q3W). Six TNBC subjects were enrolled in cohort 2 (afuresertib 100 mg PO QD + LAE005 1200 mg IV Q3W + nab-paclitaxel 100 mg/m2 IV D1, D8, Q3W). 10 TNBC subjects were enrolled in cohort 3 (afuresertib 125 mg PO QD + LAE005 1200 mg IV Q3W + nab-paclitaxel 100 mg/m2 IV D1, D8, Q3W). 2, 0, 2 dose-limiting toxicity (DLT) cases were reported out of 6, 6, 7 DLT evaluable subjects in cohort 1, 2, 3, respectively. DLTs were grade 3 rash (including rash, rash maculopapular, and erythema multiforme) and fever. The most common treatment-emergent AEs were rash (90.9%), white blood cell count decreased (81.8%), and neutrophil count decreased (77.3%). The most common grade 3 or above AEs were neutrophil count decreased (40.9%), white blood cell count decreased (36.4%), rash (18.2%) and lymphocyte count decreased (18.2%). Most of the AEs are manageable, reversible, and recovered after routine treatments. The median follow-up time for 19 TNBC subjects was 16.0 months (min-max: 8.7-28.9 months). The median PFS of these TNBC subjects was 5.4 months (95% CI: 1.4-14.0 months). Among 14 TNBC patients who completed at least 2 cycles of treatment, 5 cases had confirmed PR (ORR 35.7%), 4 cases (28.6%) had SD as the best response. DCR was 64.3%, ORR in three cohorts was 1/2, 2/5, 2/7, respectively. The median DOR was 9.26 months (95%CI: 2.3-NE months).5 TNBC subjects were treated for more than 32 weeks, and the longest duration of treatment was 73 weeks.
Conclusions: The triplet regimen shows a manageable safety profile and encouraging preliminary activity in the drug resistant TNBC patients. This triplet regimen warrants further investigation.
Citation Format: Binghe Xu, Pin Zhang, Ying Wang, Zhongsheng Tong, Tingjing Yao, Xian Wang, Zijia Wang, Pengfei Guo, Wenyue Ma, Yong YUE. Phase I/II clinical trials of LAE005, afuresertib plus nab-paclitaxel in patients with advanced solid tumors, primarily in patients with triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT128.