On December 11, 2023 Laekna (2105.HK), a clinical-stage biotechnology company, reported the results of a phase Ib study to evaluate the efficacy and safety of afuresertib plus fulvestrant in patients with locally advanced or metastatic HR+/HER2- breast cancer who failed standard of care therapies at the 2023 San Antonio Breast Cancer Symposium (SABCS) on December 8 (Press release, Laekna Therapeutics, DEC 11, 2023, View Source;laekna-reports-afuresertib-phase-ib-breast-cancer-study-results-302011286.html [SID1234638464]).
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From May 2022 to April 2023, 20 patients (19 female and 1 male) with locally advanced or metastatic HR+/HER2- breast cancer who had failed 1-2 lines of endocrine therapy were enrolled in the Phase Ib study. The median duration of follow-up was 11 months.
As of October 16, 2023, the main study results are as follows:
– 70% of the patients were previously treated with CDK4/6 inhibitors.
– Among the total patient population, the confirmed ORR was 30% (95% CI, 11.9, 54.3), the median PFS was 7.3 months (95% CI, 3.7, NE). The disease control rate (DCR) was 80%.
– Among the 11 patients with specific biomarker alterations (PIK3CA/AKT1/PTEN), the confirmed objective response rate was 45.4% (95% CI, 16.7, 76.6), the disease control rate was 82%, and the median PFS was 7.3 months (95% CI, 3.6, 8.2).
– Among the 17 Chinese patients, the confirmed ORR was 29.4% (95% CI, 10.3, 60.0), the disease control rate was 82.4%, and the median PFS was 7.3 months (95% CI, 3.6, 8.2).
– The results demonstrated a well-tolerated safety profile of afuresertib plus fulvestrant. No dose modification was required during the safety run-in period. No patient discontinued treatment due to TEAE. No serious adverse event (SAE) was reported.
Investigators concluded that the combination therapy of afuresertib and fulvestrant has shown promising efficacy with a well-tolerated safety profile, supporting further evaluation in the upcoming Phase III part of the study.
Academician Binghe Xu, the lead investigator of the study, said: "While therapies for breast cancer are increasing, the treatment of drug resistance remains one of the clinical challenges. With the approval of the world’s first AKT inhibitor last month, patients with locally advanced or metastatic HR+/HER2- breast cancer now have new hope. The Phase Ib data of the combination therapy of afuresertib and fulvestrant are promising. I look forward to the next Phase III study of afuresertib in breast cancer."
"Biomarkers of response and/or resistance to endocrine-based therapies has become a prominent topic in the field of breast cancer treatment. It is also the central theme of the ‘Poster Spotlight Session’ in which our study was presented," said Dr. Yong Yue, Chief Medical Officer of Laekna. "Compared with the PFS data of 3-4 months for fulvestrant monotherapy[1], the median PFS of afuresertib plus fulvestrant is significantly increased to 7.3 months, with a favorable safety profile."
Lakena has initiated the Phase III pivotal trial of afuresertib plus fulvestrant in the treatment of HR+/HER2- breast cancer. The company strives to bring new hope to patients.
Notes
Breast cancer
The latest data released by the International Agency for Research on Cancer (IARC) of the World Health Organization show that the number of new cases of breast cancer in 2020 reached 2.26 million worldwide, surpassing lung cancer for the first time and becoming the world’s most prevalent cancer with 685,000 deaths. The latest epidemic data of malignant tumors in China also show that breast cancer has ranked first among women, with about 420,000 new cases each year[2].
Approximately 69% of breast cancer patients in the United States are considered HR+/HER2[3], and the proportion of this subtype among Chinese patients is 62%[4]. Although most patients with this type of breast cancer initially benefit from first/second-line endocrine ± CDK4/6 inhibitors and/or chemotherapy, most may develop drug resistance after a period, leading to treatment failure.
With further research on AKT, it has been demonstrated that factors such as PTEN loss and AKT/PIK3CA mutation can lead to excessive activation of the AKT signaling pathway, resulting in the occurrence, development, and drug resistance of tumors, especially prevalent in HR+ breast cancer. AKT has consequently emerged as a popular target for treating tumors.
Afuresertib
Afuresertib (LAE002) is an AKT inhibitor developed by Laekna. Laekna has initiated multiple clinical studies of combination therapies with Afuresertib in patients with PROC, HR+/HER2− breast cancer, mCRPC, TNBC, PD-1-resistant cervical cancer, and endometrial cancer.