FDA greenlights phase 3 study of LAE201 in mCRPC

The FDA has approved the study protocol for a phase 3 trial of LAE002 (afuresertib, an ANK inhibitor) in combination with LAE001 (a dual CYP17A1/CYP11B2 inhibitor) in patients with metastatic castration-resistant prostate cancer (mCRPC) following standard of care (SOC) treatment, according to a news release from Laekna, the developer of the combination therapy.¹

“We look forward to bringing this precision therapy to mCRPC patients who are in need of novel treatment options," says Yong Yue, MD, PhD.

The 2 therapies, in combination, are called LAE201.

"Since the phase 2 data of the combination therapy of LAE002 (afuresertib) plus LAE001 demonstrated encouraging anti-tumor activity and safety profile in patients with mCRPC, a following phase 3 pivotal trial design has been discussed with the US FDA and the approval for the protocol has been received this month," said Yong Yue, MD, PhD, Chief Medical Officer of Laekna, in the news release.¹ "The approval marks a significant milestone for Laekna. The mCRPC post 1-3 lines of SOC are difficult-to-treat late-stage cancer with poor outcomes. It is an unmet medical need worldwide.”

Data from a phase 1/2 dose escalation and dose expansion trial (NCT04060394)of LAE201 were presented at the 2023 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain.²

Overall, the study showed a median radiographic progression-free survival (rPFS) of 8.1 months with LAE201. According to the news release from Laekna, this represents a significant improvement over the historical rPFS with SOC for mCRPC, which is a median of 2 to 4 months.¹

Further, Laekna reported that 2 confirmed partial responses and 2 unconfirmed partial responses per RECIST v1.1 were observed among the 12 patients with measurable lesions at baseline.³

Regarding safety, the treatment was generally well-tolerated. Treatment-emergent adverse events (AEs) were manageable, and patients recovered following routine treatments. The most commonly reported AEs of grade 3 or higher were thrombocytopenia (7.5%), anemia (5.0%), hyperglycemia (5.0%), hyponatremia (5.0%), and hypertension (5.0%).

Serious AEs were reported in 9 (22.5%) patients, with 5 (12.5%) deemed as related to study treatment. No grade 5 AEs were observed.

In total, the multicenter, open-label, global trial included 40 patients who had progressed following 1 to 3 lines of standard therapy, including at least 1 line of abiraterone (Zytiga) or the second generation of androgen receptor antagonists. Patients in the trial were enrolled across 18 clinical trial sites in the United States and 5 sites in South Korea.

For the study, patients received 75 mg LAE001 twice daily/5 mg prednisone twice daily plus 125 mg afuresertib 125 mg once daily. Across all patients, the follow-up was between 1.8 to 31.3 months. The median prior lines of therapy was 2, and the median Gleason score was 9.

The primary end point for the study was rPFS.

Yue concluded in the news release,¹ “We look forward to bringing this precision therapy to mCRPC patients who are in need of novel treatment options."

References

1. Laekna announces FDA approval for the phase III clinical trial protocol of LAE002 (Afuresertib) PLUS LAE001 for the treatment of prostate cancer. News release. Laekna. Published online and accessed May 23, 2024. https://en.laekna.com/new/399.html

2. Diamond E, Kwak C, Orr D, et al. 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. Presented at: 2023 European Society for Medical Oncology Congress. October 20-24, 2023. Madrid, Spain.Abstract 1817P

3. 2023 ESMO│Laekna (2105.HK) announces phase I/II data of LAE001 plus afuresertib in mCRPC. News release. Laekna. October 24, 2023. Accessed May 23, 2024. https://en.laekna.com/new/316.html