Despite treatment with the chemoprotective agent ALRN-6924, patients with p53-mutated breast cancer receiving neoadjuvant or adjuvant therapy with docetaxel, doxorubicin, and cyclophosphamide failed to meet the trial’s primary and secondary end points of duration and incidence of severe neutropenia in cycle 1 and incidence of chemotherapy-induced alopecia, respectively.
Despite treatment with the chemoprotective agent ALRN-6924, patients with p53-mutated breast cancer receiving neoadjuvant or adjuvant therapy with docetaxel, doxorubicin, and cyclophosphamide experienced grade 4 neutropenia and alopecia in a phase 1b trial (NCT05622058), failing to meet the trial’s primary and secondary end points of duration and incidence of severe neutropenia in cycle 1 and incidence of chemotherapy-induced alopecia, respectively.1
Based on these results, the company has decided to terminate the trial and further development of ALRN-6924, which was also under evaluation as a chemoprotective agent in p53-mutated small cell lung cancer and non–small cell lung cancer (NSCLC).
“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 [adverse] effects and given the activity we had observed in our clinical trial in [patients with] small cell lung cancer receiving topotecan chemotherapy. I would like to extend a heartfelt thanks to our patients, investigators and clinical trial staff, and scientific advisors, as well as all others who have supported this trial and our efforts to advance ALRN-6924 as a chemoprotective agent. I would also like to thank our talented and truly dedicated Aileron team who have worked so diligently to advance ALRN-6924,” Manuel Aivado, MD, PhD, president and chief executive officer at Aileron Therapeutics, said in a press release.
ALRN-6924 is an MDM2/MDMX inhibitor that was initially developed as an anti-cancer agent to restore p53-dependent tumor suppression in p53 wild-type tumors. Data from clinical trials evaluating ALRN-6924 showed that the agent was well tolerated and led to complete and partial responses.
In July 2022, Aileron halted enrollment into another phase 1b trial (NCT04022876) after ALRN-6924 failed to reduce the rate of grade 3 or greater toxicity compared with placebo, missing its composite primary end point in patients with advanced p53-mutant NSCLC.2
The company announced that it is exploring strategic alternatives in conjunction with Ladenburg Thalmann & Co., Inc., which may include an acquisition, a merger, a business combination, or a sale of assets or other transactions. Further statements from the company will not be released unless or until its Board of Directors has approved a definitive course of action or it is determined that other disclosure is appropriate.
In the coming weeks, the company will move from 9 to 3 full-time employees to assist in executing the strategic alternatives review process.
“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,” Aivado concluded.