Afuresertib-Based Combination Meets Primary End Point in Phase 3 HR+ Breast Cancer Trial

Positive topline results from the pivotal phase 3 AFFIRM-205 clinical trial (NCT04851613) demonstrate that the combination of afuresertib (LAE002) and fulvestrant (Faslodex) significantly improves progression-free survival (PFS) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) locally advanced or metastatic breast cancer. The study specifically targeted patients harboring PIK3CA/AKT1/PTEN alterations who had previously progressed on or after endocrine therapy, including those treated with CDK4/6 inhibitors.¹

“We are proud to share that the [p]hase [3] clinical trial of afuresertib for breast cancer has met its primary [end point]. The treatment has brought significant and clinically meaningful improvements to patients, with the topline results clearly demonstrating best-in-class efficacy and safety profile,” said Chris Lu, PhD, chairman and CEO of Laekna, in a news release. “In response to the high unmet medical needs, we are pursuing collaborations with partners to accelerate patient access to this novel therapy in global markets.”

Pivotal Efficacy Results

The primary analysis revealed a median PFS of 7.6 months for patients receiving the afuresertib plus fulvestrant combination compared with 2.0 months for those in the placebo plus fulvestrant control arm. This represents a highly statistically significant and clinically meaningful reduction in the risk of disease progression or death, with a hazard ratio (HR) of 0.33 (P <.0001).

The data indicate that the addition of afuresertib, a potent pan-AKT inhibitor, can effectively overcome endocrine resistance in a population with limited therapeutic options. Approximately 70.5% of the 261 patients enrolled in the study had been previously treated with CDK4/6 inhibitors, a standard of care that often eventually leads to resistance mediated by the activation of the AKT pathway.

Safety and Tolerability

Beyond the efficacy outcomes, the trial reported a manageable safety profile for the once-daily oral afuresertib regimen. Discontinuation rates due to adverse events (AEs) were noted as very low, which differentiates the agent within the class of AKT inhibitors that have historically been associated with gastrointestinal and metabolic toxicities. The safety data observed in AFFIRM-205 remained consistent with findings from the preceding phase 1b study published in Nature Communications earlier this year.²

Clinical Context and Mechanism of Action

HR+/HER2– breast cancer accounts for approximately 70% of all breast cancer cases globally.³ While endocrine therapy remains the backbone of treatment, nearly half of these patients possess alterations in the PI3K/AKT/PTEN pathway, which are major drivers of resistance to hormone-based treatments.

Afuresertib is an investigational ATP-competitive inhibitor that targets all 3 AKT isoforms (AKT1, AKT2, and AKT3).¹ By blocking these nodes, the drug restores sensitivity to endocrine therapy and inhibits the survival signals that allow tumor cells to bypass hormonal blockade. Currently, afuresertib is 1 of only 2 AKT inhibitors in late-stage global development, positioning it as a potential second-in-class therapy following the regulatory approval of capivasertib (Truqap).⁴

REFERENCES

1. Positive Topline Results | Laekna’s Phase III Clinical Trial of LAE002 (afuresertib) for Breast Cancer Met Primary Endpoint. News release. Laekna. April 15, 2026. Accessed April 16, 2026. https://tinyurl.com/4sd9bbvr

2. Zhang P, Sun T, Wang Y, et al. Afuresertib plus fulvestrant for pretreated HR-positive, HER2-negative, advanced breast cancer: a phase Ib trial. Nat Commun. 2026 Feb 6;17(1):2456. doi: 10.1038/s41467-026-69225-2. PMID: 41651834; PMCID: PMC12992602.

3. Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute. Accessed April 16, 2026. https://tinyurl.com/4ay96dpu

4. FDA approves capivasertib with fulvestrant for breast cancer. News release. US FDA. Updated November 16, 2023. Accessed April 16, 2026. https://tinyurl.com/4ajuu8tt