Aileron Therapeutics (NASDAQ:ALRN), the clinical-stage leader in the field of stabilized, cell-permeating peptides to treat cancer and other diseases, today announced that the first patient has been enrolled in a Phase 2a expansion cohort intended to assess preliminary activity and safety of ALRN-6924 in combination with Pfizer’s palbociclib, also known as IBRANCE®, in cancer patients with MDM2-amplified solid tumors.
“We are excited to launch this Phase 2a expansion cohort, expanding on our ALRN-6924 clinical trial combination program,” said Vojo Vukovic, MD, PhD, and Chief Medical Officer of Aileron. “ALRN-6924 and palbociclib address the MDM2 (p53) and CDK4 (Rb) pathways, which have interdependent roles in cancer biology, and preclinical results recently presented by Aileron show synergistic activity for ALRN-6924 and palbociclib in cancer cells and animal models1. Furthermore, the MDM2 and CDK4 genes are co-amplified in many cancers. We are using this biomarker-driven approach to select cancer patients with tumors exhibiting this genetic profile. We are hopeful that a dual MDM2 and CDK4 inhibition strategy will benefit these patients.”
This Phase 2a expansion cohort is intended to assess the preliminary activity and safety of ALRN-6924 in combination with palbociclib. The trial is expected to enroll up to 25 MDM2-amplified cancer patients with advanced solid tumors that test positive for the presence of wild-type p53. The objectives of the trial include determining the overall response rate and other parameters of efficacy, as well as evaluating the safety and tolerability of the combination. Aileron expects to present preliminary data in the second half of 2019 at a medical conference.
This Phase 2a expansion cohort is intended to assess the preliminary activity and safety of ALRN-6924 in combination with palbociclib. The trial is expected to enroll up to 25 MDM2-amplified cancer patients with advanced solid tumors that test positive for the presence of wild-type p53. The objectives of the trial include determining the overall response rate and other parameters of efficacy, as well as evaluating the safety and tolerability of the combination. Aileron expects to present preliminary data in the second half of 2019 at a medical conference.
ALRN-6924 is a first-in-class, stabilized cell-permeating peptide that mimics the p53 tumor suppressor protein to disrupt the interaction with both p53-inhibitors, MDMX and MDM2. For p53 wild-type tumors, ALRN-6924 can restore p53-dependent tumor suppression. Palbociclib is an oral inhibitor of cell cycle check-point regulators CDK4/6. The MDM2 and CDK4 genes are located on chromosome 12 in close proximity to each other, with CDK4 very frequently co-amplified in patients with MDM2-amplified cancers who will be enrolled in this trial. This co-amplification provides the mechanistic rationale and suggests a potential patient benefit from combining the MDM2/MDMX-inhibitor, ALRN-6924, with the CDK4/6-inhibitor, palbociclib2.
1. 2018 San Antonio Breast Cancer Symposium abstract #1129, “The Stapled Peptide ALRN-6924, a Dual Inhibitor of MDMX and MDM2, and the CDK4/6 Inhibitors Palbociclib, Ribociclib, or Abemaciclib Synergistically Enhance Each Other’s in vitro and in vivo Anticancer Activity”
2. Laroche-Clary et al. Journal of Hematology & Oncology (2017) 10:123 DOI 10.1186/s13045-017-0482-3
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