Abstract 599P
Background
The new therapy for the patient (pt) with drug-resistant mCRPC (dr-mCRPC) is a definite unmet medical need. The ORR of dr-mCRPC pts were only 7% to 17% in second to fourth line settings. Other studies reported that AKT inhibitor plus anti-androgen is a potential treatment for dr-mCRPC. This study assessed the safety and efficacy of combination therapy of afuresertib (a AKT inhibitor) and LAE001 (a dual inhibitor of CYP17A1 (testosterone synthesis) and CYP11B2 (aldosterone synthase) in dr-mCRPC.
Methods
This is a multicenter, open-label, dose-escalation phase I study to assess the safety and to determine the the Recommended phase II dose (RP2D) of the combined therapy of LAE001/prednisone and afuresertib in mCRPC patients who failed at least 1 prior SOC. The pts in cohort 1 and cohort 2 received (LAE001 75 mg BID/prednisone 5 mg BID and afuresertib 100 mg QD) and (LAE001 75 mg BID/prednisone 5 mg BID and afuresertib 125 mg QD), respectively.
Results
As of 02/28/2021, 14 pts (8 in cohort 1 and 6 in cohort 2) received study treatment with median 8.5 months follow up. The dose of LAE001 75 mg BID/prednisone 5 mg BID and afuresertib 125 mg QD was determined as the RP2D. There were 2 DLTs reported in cohort 1 (thrombocytopenia) and cohort 2 (skin rash). The only one non-DLT grade >= 3 treatment-emergent adverse events (TEAE) in RP2D was a skin rash. The 10 evaluable pts (received at least 1 cycle of study treatment) in both cohorts were included in efficacy analysis. Two pts had a PSA response (2/10, 20%). Among 5 pts who have measurable lesions, 1 non-confirmed PR (37% tumor reduction) and 2 SDs were reported. These 10 pts on average had 3 lines of SOC. Table: 599P
| Combination Dose in Different Cohorts | PSA Responsea/ #Evaluable (%)b | # with Measurable Disease by RECIST | BOR in Pts with Measurable Disease by RECIST 1.1 | Bone Lesions Evaluations/# with Baseline Bone Lesions | |||||
| CR | PR | SD | PD | NE | SD | PD | |||
| Cohort1 - LAE001 75mg BID/prednisone 5mg BID + afuresertib 100mg QD | 1/5 (20 %) | 2 | 2 | 4/4 | |||||
| Cohort2 - LAE001 75mg BID/prednisone 5mg BID + afuresertib 125mg QD | 1/5 (20 %) | 3 | 1 | 2 | 4/4 |
a PSA response is defined as 50% reduction in best post-baseline PSA over baseline. b # PSA evaluable excludes DLT/being replaced patients who have been treated within a cycle before discontinuing treatment. Two patient without any baseline bone lesions has not shown to have new post-baseline bone lesions.
Conclusions
The combination therapy of LAE001 75mg BID/prednisone 5mg BID and afuresertib 125mg QD was determined as the RP2D. The preliminary antitumor activity under the RP2D supports the potential clinical benefit for treating dr-mCRPC and moves forward this study to phase II stage.
Clinical trial identification
NCT04060394.
Editorial acknowledgement
Legal entity responsible for the study
Laekna Limited.
Funding
Laekna Limited.
Disclosure
A. Bessudo, J.F. Strauss, D.E. Slater, C. Pieczonka: Non-Financial Interests, Institutional, Principal Investigator: Laekna Therapeutics. X. Wang, P. Guo, J. Liu, Y. Yue, C. Lu: Financial Interests, Personal, Full or part-time Employment: Laekna Therapeutics.