MSD's CTLA-4 Monoclonal Antibody Combination Therapy Licensed from Akeso Receives IND Approval in China for Advanced Solid Tumors

The latest public notice on the website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration indicates that Merck Sharp & Dohme (MSD) has received implicit approval for a clinical trial of its Class 1 new drug, MK-1308A injection, for the indication of advanced solid tumors. According to publicly available information, MK-1308A is a combination regimen comprising MK-1308 and MSD’s PD-1 inhibitor Keytruda (pembrolizumab), wherein MK-1308 is an anti-CTLA-4 antibody licensed by MSD from Akeso Biopharma.

Source: CDE Official Website

Public information indicates that MK-1308, also known as quavonlimab, was initially discovered by Akeso Biopharma. In 2015, MSD and Akeso Biopharma reached an agreement whereby MSD obtained exclusive global rights for the development and commercialization of MK-1308. MK-1308 is a novel humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting CTLA-4. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is one of the primary negative regulators of T-cell responses. MK-1308 binds to CTLA-4 and blocks its interaction with the ligands CD80 and CD86, thereby inhibiting CTLA-4 function and enhancing the ability of T cells to kill tumor cells.

Keytruda is a blockbuster PD-1 inhibitor developed by Merck Sharp & Dohme (MSD). It activates T lymphocytes by blocking the binding of PD-1 to PD-L1 and PD-L2, thereby enhancing their ability to recognize and attack cancer cells. Since its launch, the drug has been approved for the treatment of various cancers, including melanoma, non-small cell lung cancer, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, and triple-negative breast cancer (TNBC), among others.

According to information on the ClinicalTrials.gov website, MSD is currently conducting multiple studies on MK-1308A. These include a Phase 1/2 open-label, multi-arm, multicenter clinical trial designed to evaluate the efficacy of the MK-1308/Keytruda combination therapy (also known as MK-1308A) in patients with advanced solid tumors. The indication for this combination therapy approved for clinical research in China is also advanced solid tumors.

Image

At the International Association for the Study of Lung Cancer (IASLC) North America Conference on Lung Cancer held in October 2020, researchers reported the results of a Phase 1/2 clinical trial of the MK-1308/Keytruda combination therapy. The study aimed to evaluate the safety and tolerability of the combination therapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) and to determine the recommended Phase 2 dose (RP2D) for subsequent Phase 2 clinical studies.

The data showed that in patients with non-small cell lung cancer (NSCLC), the overall objective response rate (ORR) was 35.1%; the median progression-free survival (PFS) in the overall population was 6.1 months, and the PFS rate at 6 months was 54%; the median overall survival (OS) in the overall population was 16.5 months, and the OS rate at 12 months was 67%. Exploratory analysis results indicated that among 134 NSCLC patients, 110 had tumor PD-L1 expression data, and the level of tumor PD-L1 expression in patients who responded to the combination therapy regimen was generally higher than that in non-responders. Meanwhile, researchers observed that the ORR in PD-L1-positive patients was 39%, while the ORR in PD-L1-negative patients was 33%.

Overall, the study results demonstrated that the MK-1308/Keytruda combination therapy, as a first-line treatment for advanced non-small cell lung cancer (NSCLC), exhibited antitumor activity across all dose levels with a favorable overall safety profile. Furthermore, a dose of 25 mg administered once every 6 weeks (Q6W) was identified as the recommended phase 2 dose for the MK-1308/Keytruda combination regimen.

Congratulations on the approval of the MK-1308/Keytruda combination therapy for clinical trials in China. We hope that subsequent clinical trials of this combination therapy will proceed smoothly, bringing new treatment options to patients as soon as possible.

▽Follow [WuXi AppTecDe】WeChat Official Account