Article Text
Abstract
Introduction AKT inhibitor was reported to be a potential treatment for drug-resistant (including ICI-resistant) tumors by reducing AKT activity. Afuresertib is a pan-AKT inhibitor that showed clinical efficacy in multiple tumors. The objective of phase I part is to assess the safety and efficacy of afuresertib + sintilimab + nab-paclitaxel in advanced solid tumors, primarily in CC (cervical cancer) and EC (endometrial cancer).
Methods This is a multi-center, open-label, dose-escalation study (part I). Patients with at least 1 prior systemic anti-cancer treatment (include neoadjuvant/adjuvant), ECOG 0-2 are eligible. Efficacy evaluation is based on RECIST 1.1. Dose escalation uses Bayesian optimal interval (BOIN).
Results Up to Apr 10, 2024, 18 subjects were dosed. The most common≥ grade 3 AEs were white blood cell count decreased (27.8%), rash/rash maculo-papular (27.8%) and anemia (22.2%). Most of the AEs are manageable and reversible. Of 16 CC/EC subjects, the median prior line of systematic anti-tumor therapy was 1 (0-3), including chemotherapy, bevacizumab or ICIs. The median follow-up time was 10.0 months (1.1-21.4 months). The median PFS was 6.1 months (95% CI: 3.0-8.2 months). Out of the 13 CC/EC subjects who underwent tumor assessment, the confirmed ORR is 61.5% (95% CI: 31.6%-86.1%), DOR is 5.5 months (95% CI: 3.5-NR), DCR is 92.3% (95% CI: 64.0%-99.8%).
Conclusion/Implications The triplet regimen demonstrates a manageable safety profile and promising anti-tumor activity, as evidenced by high ORR and DCR. This study supports a further clinical study evaluating the triple regimen as a potential treatment for patients with advanced or metastatic CC and EC.