Study Underway to Test ALRN-6924 in p53-Mutated Non–Small Cell Lung Cancer

A double-blind, randomized, placebo-controlled phase 1b trial (NCT04022876) is currently recruiting patients with advanced p53-mutated non­–small cell lung cancer (NSCLC) in order to determine the safety and efficacy of ALRN-6924, and reduce chemotherapy toxicity in this patient population, according to a press release by Aileron Therapeutics.

Approximately 50% of new NSCLC cases annually test positive for a p53 mutation. ALRN-6924, an investigational MDM2/MDMX dual inhibitor, is meant to protect healthy cells through a process known as chemoprotection. 

“Proactively protecting patients against chemotherapy-induced toxicities that impact bone marrow cells and other cells throughout the body closely aligns with our mission to improve the health and quality of life for patients,” said Nashat Gabrail, MD, founder of the Gabrail Cancer Center in Canton, Ohio, president of Innovative Community Oncology Practices (ICOP) and an investigator in the ALRN-6924 NSCLC trial, in a press release.

The study (NCT04022876) aims to enroll 60 patients who are currently undergoing treatment with first-line carboplatin plus pemetrexed with or without immune checkpoint inhibitors. The study will have 2 cohorts, an NSCLC cohort and a small cell lung cancer cohort (SCLC). The SCLC cohort has been completed. In the NSCLC cohort, the primary outcome is the proportion of completed treatment cycles that are free of grade 3 or higher toxicities such as neutropenia, anemia, thrombocytopenia, and febrile neutropenia, while also being free of chemotherapy dose reduction and the use of growth factors and transfusions. The primary end point of the SCLC cohort is the rate of treatment-related grade 3/4 adverse events (AEs).

During part 1, patients with SCLC received ALRN-6024 plus topotecan. Patients with NSCLC who will be treated in Part 2 will be randomized 1:1 to either receive carboplatin, pemetrexed, and a placebo or a combination of carboplatin and pemetrexed plus ALRN-6924.

In order to participate in the NSCLC cohort, patients must have confirmed stage IV NSCLC, have the presence of 1 or more p53 mutation(s), have measurable disease using RECIST v1.1, an ECOG performance status of 0-1, adequate hematologic status, and adequate hepatic and renal functioning. Patients with advanced NSCLC with an EGFR mutations or ALK rearrangement or other actionable gene mutations with approved targeted therapies, patients who are candidates for anti-PD-1 monotherapy, those with active central nervous system metastases, or those who experience significant weight loss amounting to 15% or more of their body weight within 4 weeks prior to enrollment are not eligible to participate.

“This is a significantly unaddressed need impacting nearly every patient who undergoes chemotherapy. When devising treatment strategies for today’s cancer patients, the use of targeted therapies is certainly preferred when possible. We are proud to participate in this trial to help explore the potential of ALRN-6924 as a novel chemoprotective agent that utilizes a biomarker-driven approach, thereby potentially bringing the promise of precision medicine to the field of supportive care drugs,” Gabrail added.

The commencement of the NSCLC cohort comes on the heels of positive results from the SCLC cohort, which enrolled 26 individuals. The median number of cycles of topotecan completed was 3 and 12% of patients required a dose reduction. The disease control rate was 64% and grade 3/4 anemia, thrombocytopenia, and neutropenia were reported in 24%, 36% and 88% respectively. According to the analysis, the historic rates of those AEs in this patient’s population is 63%, 70%, and 86% respectively. No grade 3/4 nausea, vomiting, or diarrhea was reported.2

In the United States, the NSCLC cohort is currently recruiting in Michigan, Ohio. The study is also recruiting international in Bosnia and Herzegovina, Poland, Serbia, and Spain.

_REFERENCES:

_{1. Aileron Therapeutics announces initiation of randomized, double-blind, placebo-controlled trial of ALRN-6924 in patients with advanced non-small cell lung cancer (NSCLC). News release. Aileron Therapeutics. July 1, 2021. Accessed July 1, 2021. https://bit.ly/3jzp55w.}

_{2. Andric Z, Ceric T, Stanetic M, et al. Prevention of chemotherapy-induced myelosuppression in SCLC patients treated with the dual MDMX/MDM2 Inhibitor ALRN-6924. Abstract presented at the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, October 24 – October 25, 2020. Accessed July 1, 2021. https://bit.ly/3yd9Hzz.}