Ascentage Pharma has revealed to have entered into a clinical collaboration with MSD to study the combination of APG-115 with the latter's KEYTRUDA (pembrolizumab) for the treatment of advanced solid tumours.
APG-115 has been designed by Ascentage Pharma as an orally administered, selective, small-molecule inhibitor of the MDM2-p53 PPI.
KEYTRUDA, on the other hand, is an anti-PD-1 therapy, which has multiple approvals across various cancer indications in different parts of the world, as a monotherapy and also in combination with other drugs.
As per the agreement terms, Ascentage Pharma will fund an open-label, multicentre, phase Ib/II study called NCT03611868 for assessing the safety and efficacy of the APG-115, KEYTRUDA combination in multiple cohorts of solid tumours.
The patients to take part in the trial may include those having non-small cell lung cancer (NSCLC), melanoma, liposarcoma, urothelial cancer, malignant peripheral nerve sheath tumour (MPNST), and ATM mutated/p53 WT tumours resistant or relapsed to PD-1/PD-L1 treatment or without previous PD-1/PD-L1 treatment.
The phase 2 part of the trial has been initiated and is likely to feature 80 patients at multiple sites across the US.
Ascentage Pharma and MSD will use a joint development committee to exchange information about the clinical trial.
According to Ascentage Pharma, preclinical studies have shown that APG-115 helped in promoting the production of proinflammatory cytokines in T cells, improved CD4+ T cell activation, and increased PD-L1 expression on various tumour cells.
Furthermore, improved antitumour activity was shown across various tumour models after the combination of APG-115 with PD-1 blockade.
Results of the phase 1b part of the NCT03611868 trial were published recently at ASCO2020 and showed that APG-115, pembrolizumab combination is well-tolerated, with promising anti-tumour effects in various types of tumour.
Ascentage Pharma chairman and CEO Dajun Yang said: “We are excited to collaborate with MSD, a pharmaceutical industry leader. APG-115 is a key drug candidate in our development pipeline targeting apoptosis, with great potential in the treatment of advanced solid tumours.
“Based on the promising Phase Ib data, we are looking forward to working closely with MSD to further study the combination of APG-115 with KEYTRUDA, potentially offering more effective treatment options to patients with advanced solid tumours.”