Aileron Therapeutics has entered a clinical trial collaboration with Pfizer to evaluate the combination of ALRN-6924 and palbociclib in MDM2-amplified cancers.
The Phase Ib trial is expected to start enrolling patients with solid tumours in the first quarter of next year.
Pfizer will support the trial by providing a supply of its drug palbociclib for testing with Aileron's ALRN-6924.
The first-in-class, stabilised cell-permeating peptide ALRN-6924 mimics the p53 tumour suppressor protein to disrupt the interaction with endogenous inhibitors MDMX and MDM2.
Aileron Therapeutics president and CEO Manuel Aivado said: “We are excited about this combination trial with Pfizer’s palbociclib. The combination of ALRN-6924 and palbociclib demonstrated enhanced antitumor activity and meaningfully delayed tumour growth in animal models over single agents alone.
“We believe the combination of these two drugs represents a complementary attack on the proliferation of cancer cells that may benefit patients with a variety of different cancers.”
ALRN-6924 will be capable of restoring p53-dependent tumour suppression for p53 wild-type tumours.
Also known as IBRANCE, Pfizer’s palbociclib is an oral inhibitor of cell cycle check-point regulators CDK4/6.
The MDM2 and CDK4 genes are located close to one another on chromosome 12, with CDK4 very frequently co-amplified in the MDM2-amplification-positive patients who will be enrolled in the trial.
This co-amplification further suggests a potential patient benefit from combining the MDM2/MDMX-inhibitor ALRN-6924 with the CDK4/6-inhibitor palbociclib.
The stabilised helical structure of Aileron’s peptides allows the design of cell-permeating therapeutic agents with large molecular surfaces for optimal target binding properties. This will result in new drugs such as ALRN-6924.