1817P - A phase I/II efficacy and safety study of LAE001/prednisone and afuresertib in patients with metastatic castration-resistant prostate cancer (mCRPC) following 1-3 lines of standard of care

Background

New therapy for mCRPC patients refractory to the second-generation anti-androgen or androgen receptor hormonal therapy and/or chemotherapy is a definite unmet medical need. The ORR and median rPFS of refractory mCRPC patients are 7% to 17% and 2 to 4 months in second to fourth line settings, respectively. Studies have reported that AKT inhibitor plus an anti-androgen inhibitor is a potential treatment for refractory mCRPC with a longer rPFS and a better ORR compared to standard of care (SOC).

Methods

This is a multicenter, open-label, global phase I/II study to assess the efficacy and safety of combination therapy of LAE001 (a dual inhibitor of CYP17A1 and CYP11B2)/prednisone plus afuresertib (an AKT inhibitor) in refractory mCRPC patients who failed 1-3 lines of SOC. The patients in phase I and phase II received the combination therapy of LAE001 75 mg BID/prednisone 5 mg BID plus afuresertib 125 mg QD were included in analysis.

Results

The study enrollment was completed on 01Mar2023. At the data cut-off date on 25Apr2023, 40 patients (6 from phase I and 34 from phase II) were treated and followed-up between 1.8 to 31.3 months. The median prior lines of therapy were 2 and median Gleason score was 9. Seven rPFS events were observed and 26 patients are still in the study without radiographic tumor progression. The rPFS data is expected to be mature and will be reported at the meeting. Partial response per RECIST 1.1 were observed in 3 of 10 patients who had measurable lesions at baseline and at least one post-baseline tumor assessment. The most commonly reported AEs (≥ Grade 3) were thrombocytopenia (7.5%), anaemia (5.0%), hyperglycaemia (5.0%), hyponatraemia (5.0%), and hypertension (5.0%). SAEs were reported in 9 patients (22.5%), 5 (12.5%) were assessed as related to study treatment. No related G5 AE occured.

Conclusions

The combination therapy demonstrated clinical benefit and a tolerable safety profile in mCRPC patients who failed multiple lines of SOC. The preliminary results warrant further evaluation in a phase III pivotal trial.

Clinical trial identification

NCT04060394.

Editorial acknowledgement

Legal entity responsible for the study

Laekna Limited.

Funding

Laekna Limited.

Disclosure

P. Guo, K. Ma, E. Cao, Y. Yue: Financial Interests, Personal, Full or part-time Employment: Laekna Limited. All other authors have declared no conflicts of interest.