Aileron Therapeutics Announces First Patients Treated in Phase 1b Trial of ALRN-6924 in Patients With p53-Mutated Neoadjuvant Breast Cancer

Aileron Therapeutics recently announced it has treated the first patients in its Phase 1b randomized, controlled clinical trial evaluating ALRN-6924 to protect against chemotherapy-induced neutropenia and other bone marrow toxicities, as well as toxicities outside of the bone marrow in patients with p53-mutated breast cancer who are being treated with doxorubicin plus cyclophosphamide and docetaxel (AC+D).

Nearly 1 million patients each year are diagnosed with a p53-mutated cancer in the US. Aileron is pioneering a precision medicine-based approach that is designed to enable the selective chemoprotection of healthy, normal cells in patients with p53-mutated cancers who are receiving chemotherapy without protecting their cancer cells from chemotherapy.

“Dosing of the first patients in our Phase 1b trial in patients with p53-mutated neoadjuvant breast cancer is an important step in advancing our vision to bring chemoprotection to all patients with p53-mutated cancer regardless of the type of cancer or chemotherapy,” said Manuel Aivado, MD, PhD, President and Chief Executive Officer at Aileron Therapeutics. “The severe toxicity profile of AC+D will enable us to evaluate ALRN-6924’s protective effect against multiple chemotherapy-induced toxicities. Moreover, this breast cancer trial may potentially open an additional regulatory opportunity with established precedents for supportive care drug approvals.”

AC+D, a standard of care for patients with neoadjuvant breast cancer, is a highly effective but also highly toxic chemotherapy regimen. It causes severe neutropenia in up to 75% of patients and alopecia in approximately 90% of patients.

Aileron has previously presented non-clinical proof of mechanism data demonstrating ALRN-6924’s ability to arrest cell cycling and protect against chemotherapy-induced toxicities in bone marrow stem cells (in vitro), epithelial gut mucosa cells (in vivo), and hair follicles and their stem cells (ex vivo). The company has also presented proof of mechanism data for cell cycle arrest in bone marrow stem cells and hair follicle cells in healthy human volunteers, and proof of concept data for reduced multilineage bone marrow toxicities in patients with small cell lung cancer (SCLC) treated with topotecan.

The Phase 1b clinical trial will evaluate the safety, tolerability and protective effect of ALRN-6924 against hematologic toxicities and other toxicities in patients with neoadjuvant breast cancer. Anticipated to enroll 30 patients, the trial involves a parallel group design with a dose expansion cohort. Patients will receive doxorubicin plus cyclophosphamide (AC) on Day 1 of each 3-week cycle for 4 cycles, and then docetaxel (D) on Day 1 of each 3-week cycle for 4 cycles. In part 1 (Dose Evaluation), a control group of 8 patients with p53-wild type breast cancer (i.e., non-p53-mutated) will receive AC+D without ALRN-6924. Patients with p53-mutated breast cancer on the same AC+D regimen will be randomized to concurrently receive ALRN-6924 at 0.3 mg/kg ALRN-6924 (n=6) or at 0.6 mg/kg ALRN-6924 (n=6). ALRN-6924 is given as IV infusion on study days 0, 1 (day of chemotherapy) and 2. In Part 2 (Dose Expansion), 10 patients will receive the same AC+D regimen and the ALRN-6924 dose selected in Part 1.

In 4Q2022, Aileron anticipates reporting initial interim results from patients treated with AC in Part 1 of the breast cancer trial. In addition, the company anticipates reporting interim results from its ongoing Phase 1b randomized, double-blind, placebo-controlled clinical trial of ALRN-6924 in patients with non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immune checkpoint inhibitors in June 2022 and topline results from that trial in 4Q2022.

Aileron is a clinical-stage chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients’ lives. ALRN-6924, our first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only reported chemoprotective agent in clinical development to employ a biomarker strategy, in which we exclusively focus on treating patients with p53-mutated cancers. Our targeted strategy is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients’ quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy. For more information, visit aileronrx.com.