On July 6, 2020 Ascentage Pharma (6855.HK), a global, clinical-stage biotechnology company developing novel therapies for cancers, chronic hepatitis B (CHB), and senesce diseases, reported a clinical collaboration with MSD to evaluate the combination of APG-115, Ascentage’s MDM2-p53 inhibitor, and KEYTRUDA(pembrolizumab), MSD’s anti-PD-1 therapy, for the treatment of patients with advanced solid tumors (Press release, Ascentage Pharma, JUL 6, 2020, View Source [SID1234561671]).

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Under the agreement, Ascentage will sponsor an open-label, multicenter, phase Ib/II study (NCT03611868) is designed to evaluate the safety and efficacy of APG-115 with KEYTRUDA in multiple cohorts of solid tumors (i,e., NSCLC, melanoma, Urothelial cancer, Liposarcoma, MPNST and ATM mutated/p53 WT tumors resistant or relapsed to PD-1/PD-L1 treatment or without previous PD-1/PD-L1 treatment). The Phase II portion of the study has initiated and is expected to enroll 80 patients at multiple sites in the US. MSD and Ascentage will use a joint development committee to exchange information about the study.

Preclinical studies demonstrated that APG-115 promoted the production of proinflammatory cytokines in T cells, enhanced CD4+ T cell activation, and increased PD-L1 expression on various tumor cells. Enhanced antitumor activity was demonstrated in various tumor models after APG-115 was combined with PD-1 blockade. Results of the phase 1b portion of this trial was recently published at ASCO (Free ASCO Whitepaper)2020 and demonstrated that APG-115 in combination with pembrolizumab is well-tolerated, with encouraging anti-tumor effects in several tumor types.

"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 tumors," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "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 tumors."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About APG-115

APG-115 is an orally administered, selective, small-molecule inhibitor of the MDM2-p53 PPI. APG-115 has strong binding affinity to MDM2 and is designed to activate p53 tumor suppression activity by blocking the MDM2-p53 PPI. Ascentage Pharma has previously commenced three clinical trials of APG-115 in the US, including a Phase I study as single agent, a Phase Ib/II study in combination with pembrolizumab for treatment of metastatic melanoma and other advanced solid tumors, and a Phase I/II study as a single agent or in combination with chemotherapy for treatment of salivary gland cancer. APG-115 is the first MDM2-p53 inhibitor to enter clinical studies in China. A Phase I study as a single agent, and a Phase Ib study as a single agent or in combination with chemotherapy for treatment of AML (acute myeloid leukemia) or MDS (myelodysplastic syndrome) are ongoing in China.