Phase 1b Trial of ALRN-6924 for p53-Mutated Breast Cancer Terminated


With the main end points of incidence of severe neutropenia and alopecia not met in the phase 1b trial of ALRN-6924 for patients with p53-mutated breast cancer, Aileron Therapeutics has decided to end the trial.

Initial data from a phase 1b chemoprotection trial of ALRN-6924 in patients with p53-mutated breast cancer (NCT05622058) showed that patients experienced severe, grade 4 neutropenia and alopecia, failing to meet the main end points of the trial, according to Aileron Therapeutics.

Investigators evaluated the primary end points of the duration and incidence of severe neutropenia in cycle 1 and the secondary end point of incidence of chemotherapy-induced alopecia. Based on these results, the company has decided to end the phase 1b breast cancer trial and terminate further development of ALRN-6924.

“We are very disappointed by these initial findings from our breast cancer trial, given the significant unmet need of cancer patients who must endure a wide range of chemotherapy-induced side effects and given the activity we had observed in our clinical trial in small cell lung cancer patients receiving topotecan chemotherapy,” said Manuel Aivado, MD, PhD, president and chief executive officer at Aileron Therapeutics, in the press release.

ALRN-6924 is an MDM2/MDMX inhibitor originally developed as an anti-cancer agent to restore p53-dependent tumor suppression in p53 wild-type tumors. Investigators evaluated ALRN-6924 as an anti-cancer agent in multiple clinical trials, including a single-agent phase 1 trial in patients with solid tumors and lymphomas patients (NCT02264613), in a single-agent phase 2a trial for the treatment of patients with peripheral T-cell lymphoma (NCT02264613), in a single-agent and Ara-C-combination phase 1/1b trial for patients with acute myeloid leukemia and myelodysplastic syndrome (NCT02909972), and in a phase 2a combination trial of ALRN-6924 and palbociclib in patients with tumors harboring MDM2 amplifications (NCT02909972).

Each of these trials led investigators to the conclusion that ALRN-6924 was well-tolerated, as there was evidence of single-agent anti-tumor activity, including complete and partial responses. Additionally, 3 clinical trials of ALRN-6924 have been conducted evaluating the agent in p53-mutated small cell lung cancer, non–small cell lung cancer, and breast cancer.

However, further development of ALRN-6924, which was also under evaluation as a chemoprotective agent in p53-mutated SCLC and NSCLC, has been ended based on the finding from the phase 1b open-label trial which evaluated ALRN-6924 in patients with breast cancer receiving neoadjuvant or adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide.

According to the press release, the company is exploring strategic alternatives with Ladenburg Thalmann & Co., Inc., which could consist of an acquisition, a merger, a business combination, a sale of assets, or another type of transaction. Additional detail will not be commented on until the Board of Directors have approved a definitive course of action or until another disclosure is determined to be appropriate.

“We certainly hoped for a much different outcome for patients, but it is imperative that we now shift our focus toward conserving our resources as we explore strategic alternatives to maximize shareholder value,” concluded Aivado.

Aileron Therapeutics announces termination of phase 1b breast cancer chemoprotection trial and exploration of strategic alternatives. News release. Aileron Therapeutics. February 21, 2023. Accessed February 22, 2023.
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