Abstract 597P
Background
Abiraterone, a CYP17 enzyme inhibitor, blocks the synthesis of androgens but causes the hyperaldosteronism that requires long term steroid use. The long term steroid use may cause serious side effects. LAE001 is a novel dual inhibitor of CYP17 and CYP11B2 (aldosterone synthase) that blocks both androgen and aldosterone synthesis. This study provided clinical evidences that LAE001 monotherapy is a safe medicine that can achieve androgen inhibition without hyperaldosteronism in patients with mCRPC.
Methods
In phase Ia of the study, mCRPC pts were enrolled in a 3 + 3 design to evaluate LAE001 given in 4 dose cohorts. The safety, tolerability, maximal tolerated dose (MTD) and RP2D are the primary objectives, whereas PSA response, pharmacokinetics, and pharmacodynamics are the secondary objectives of this study.
Results
As of Feb 28, 2021, 17 pts (6, 5, 3, 3 pts in the 50, 75, 100 and 125 mg BID cohorts, respectively) enrolled in the phase Ia part and had a median 14 months follow up (1-22 months). Based on safety data, 50mg BID of LAE001 was selected as the RP2D; no DLT or related serious adverse event (SAE) or AE leading to discontinuation was reported. The most frequent (>2 pts) AEs under RP2D were Hypokalaemia (3/6) and Hyperglycemia (3/6), mostly grade 1. Across cohorts, grade >=3 AEs in >=10% pts were Hypokalaemia (7/17), Platelet count decrease (3/17), and Hypertension (3/17). Efficacy analyses include 13 pts who were treated > 1 cycle. 2 pts (50mg) had a PSA response that sustained for >52 weeks. 8 pts had a >50% best PSA decline from baseline, among whom 4 pts had >90% PSA decline from baseline. In 4 pts with baseline measurable lesions, 1 PR, 2 SDs and 1 PD were observed. All pts were SDs based on bone scans. Table: 597P
| Dose | PSA Response/ #Evaluable (%) | # objective response /# baseline measurable disease | # response /# baseline bone lesion | ||||
| CR | PR | SD | PD | SD | PD | ||
| 50mg | 4/6 (67%) | 1/1 | 6/6 | ||||
| 75mg | 2/3 (67%) | 1/1 | 3/3 | ||||
| 100mg | 1/3 (33%) | 1/1 | 3/3 | ||||
| 125mg | 1/1 (100%) | 1/1 |
PSA response is defined as 50% reduction in best postbaseline PSA from baseline.4 patients with only baseline non-target lesions were non CR/non PD by the cut off date. 5 patients without any baseline lesions have not shown to have new post-baseline lesions.1 patient without any baseline bone lesions has not shown to have new post-baseline bone lesions.
Conclusions
LAE001 monotherapy is safe and well-tolerated at 50mg BID level (RP2D). The preliminary antitumor activity of LAE001 monotherapy at RP2D level supports the potential clinical benefit of treating pts with mCRPC. Further expansion phase Ib at RP2D is ongoing.
Clinical trial identification
NCT03843918.
Editorial acknowledgement
Legal entity responsible for the study
Laekna Limited.
Funding
Laekna Limited.
Disclosure
D. Ye: Financial Interests, Institutional, Principal Investigator: Fudan University Shanghai Cancer Center. R. Liu: Financial Interests, Institutional, Full or part-time Employment: Laekna Therapeutics, Shanghai, Co., Ltd. H. Luo: Financial Interests, Institutional, Principal Investigator: Chongqing University Cancer Hospital. W. Han: Financial Interests, Institutional, Principal Investigator: Hunan Cancer Hospital. X. Lu: Financial Interests, Institutional, Other, Sub-Investigator: Fudan University Shanghai Cancer Center. L. Cao: Financial Interests, Institutional, Full or part-time Employment: Laekna Therapeutics, Shanghai, Co., Ltd. P. Guo: Financial Interests, Institutional, Full or part-time Employment: Laekna Therapeutics, Shanghai, Co., Ltd. J. Liu: Financial Interests, Institutional, Full or part-time Employment: Laekna Therapeutics, Shanghai, Co., Ltd. Y. Yue: Financial Interests, Institutional, Leadership Role: Laekna Therapeutics, Shanghai, Co., Ltd. C. Lu: Financial Interests, Institutional, Leadership Role: Laekna Therapeutics, Shanghai, Co., Ltd.