Found 2 Presentations For Request "LAE001"
599P - A phase I dose-escalation study of LAE001/prednisone plus afuresertib in patients with metastatic castration-resistant prostate cancer (mCRPC) following standard of care (SOC) treatment
- Alberto Bessudo (Encinitas, CA, United States of America)
Abstract
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. 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.
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
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.
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.
597P - A phase I dose-escalation study of LAE001 in patients with metastatic castration-resistant prostate cancer (mCRPC)
- Dingwei Ye (Shanghai, China)
Abstract
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. 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.
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
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.
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.