- First and only chemoprotective therapy in clinical development that utilizes a biomarker strategy designed to protect patients with p53-mutated cancers from chemotherapy-induced toxicities and side effects
- Treatment with ALRN-6924 prior to topotecan administration resulted in a protective effect against severe chemotherapy-induced bone marrow toxicities in patients with p53-mutated small cell lung cancer (SCLC)
- Robust and clinically meaningful protection against toxicities observed with 0.3 mg/kg dose of ALRN-6924
- Aileron to host conference call and webcast on Monday, October 26, 2020 at 8:30 a.m. ET to discuss the data and its clinical development strategy to expand chemoprotection to multiple p53-mutated cancers and chemotherapies
WATERTOWN, Mass., Oct. 24, 2020 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN) today announced new positive clinical data from its ongoing Phase 1b trial demonstrating clinical proof of concept that treatment with ALRN-6924 prior to second-line topotecan administration resulted in a protective effect against severe anemia, thrombocytopenia and neutropenia in patients with p53-mutated small cell lung cancer (SCLC). The results are being featured today in a late-breaking poster presentation entitled, “Prevention of Chemotherapy-induced Myelosuppression in SCLC Patients Treated with Dual MDM2/MDMX Inhibitor ALRN-6924” (online here) at the 32nd EORTC-NCI-AACR Annual (ENA 2020) Symposium on Molecular Targets and Cancer Therapeutics.
Chemotherapy, the backbone of treatment for millions of cancer patients, is unselective, meaning it cannot distinguish between cancer cells and healthy cells. As a result, chemotherapy destroys both cancer cells and rapidly dividing healthy cells, such as bone marrow cells, hair follicle cells and skin cells, among others. ALRN-6924 is the first and only chemoprotective therapy in clinical development that utilizes a biomarker strategy. Specifically, ALRN-6924 is a cell-permeating peptide drug designed to work intracellularly, activating wild-type p53 to selectively shield healthy cells from chemotherapy in patients who harbor p53-mutant tumors, approximately 50% of all cancer patients, without interrupting chemotherapy’s targeting of cancer cells.
“These proof-of-concept results for ALRN-6924 bring us a major step closer toward our goal of creating a new paradigm of proactive prevention of chemotherapy-induced side effects to address a significant unmet need among cancer patients,” said Manuel Aivado, M.D., Ph.D., President and CEO of Aileron. “As a medical oncologist, I appreciate that physicians need assurance that a chemoprotective agent will not reduce the efficacy of chemotherapy or promote tumor growth. Designed to shield only healthy, non-p53-mutated cells and leave p53-mutated cancer cells fully vulnerable to chemotherapy, we believe ALRN-6924 provides that assurance. With ALRN-6924, we believe we have the potential to ultimately bring chemoprotection to patients across a broad set of cancer types, improving their quality of life and enhancing their anti-cancer response to chemotherapy.”
Dr. Vojislav Vukovic, M.D., Ph.D., Chief Medical Officer at Aileron, commented, “We are extremely pleased to have achieved clinical proof of concept in our ongoing Phase 1b trial. ALRN-6924 has demonstrated the ability to protect very sick patients with SCLC against severe and life-threatening toxicities and side effects that are associated with a chemotherapy that is known to be highly toxic to the bone marrow. Importantly, we now have validation to expand clinical development into other types of p53-mutated cancers and chemotherapies and pursue our long-term vision to bring chemoprotection to all patients with p53-mutated cancers regardless of cancer type or chemotherapy.”
Data Highlights
As of August 31, 2020, the data cut-off for this data presentation, a total of 26 adult patients were enrolled in the dose optimization part of the ALRN-6924 Phase 1b trial, evaluating treatment with ALRN-6924 given 24 hours prior to chemotherapy. 18 patients were enrolled across three ALRN-6924 dose levels (1.2 mg/kg, 0.6 mg/kg and 0.3 mg/kg) and an additional eight (8) patients were enrolled in a 0.3 mg/kg expansion cohort. 25 of these patients were evaluable per the trial protocol. ALRN-6924 was administered 24 hours before each dose of topotecan. Topotecan (1.5 mg/m2) was administered on days 1 through 5 of every 21-day treatment cycle. In the trial, toxicities were evaluated using the National Cancer Institute’s (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Per the Phase 1b trial protocol, patients were not permitted to receive prophylactic G-CSF treatment in cycle 1.
Across all ALRN-6924 dose levels, Grade 3/4 anemia, Grade 3/4 thrombocytopenia and Grade 4 neutropenia (defined as