Merck's CTLA-4 Monoclonal Antibody Quavonlimab (MK-1308), In-Licensed from Akeso for $200M, Advances to Phase 3 Trial in First-Line Clear Cell Renal Cell Carcinoma

Source: Yiyao Guanlan

On June 16, Akeso announced in a press release that quavonlimab (MK-1308), its CTLA-4 monoclonal antibody licensed to MSD for $200 million, has entered Phase 3 clinical trials. Currently, a Phase 3 clinical trial for the first-line treatment of advanced clear cell renal cell carcinoma (ccRCC) has been initiated, designed to evaluate the efficacy and safety of MK-1308A (MK-1308 + Keytruda) in combination with Lenvima versus Keytruda in combination with Lenvima.

Clear cell renal cell carcinoma is a common subtype of renal cell carcinoma (RCC), accounting for approximately 70% of all RCC cases. For patients with advanced clear cell renal cell carcinoma, first-line treatment options include PD-1/PD-L1 inhibitors in combination with CTLA-4 inhibitors or vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (TKIs). However, approximately 20% to 30% of RCC patients present with metastatic disease at diagnosis, and a subset of patients will ultimately experience disease progression following treatment. The treatment prognosis for these patients remains unfavorable.

Publicly available information indicates that MK-1308 was initially discovered by Akeso. In 2015, Akeso licensed it to MSD for a total consideration of $200 million, granting the latter exclusive global development and commercialization rights for the drug. As described, MK-1308 is a novel humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting CTLA-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 ligands CD80 and CD86, thereby inhibiting CTLA-4 function and enhancing T cell-mediated antitumor activity.

Currently, MK-1308 has become a key component of Merck Sharp & Dohme's (MSD) oncology pipeline. According to an investor conference call held by Merck Sharp & Dohme during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, the combination therapy of MK-1308 and Keytruda (MK-1308A) has been evaluated for efficacy in six studies, covering five cancer types including renal cancer, liver cancer, microsatellite instability-high (MSI-H) colorectal cancer, and melanoma. Meanwhile, efficacy data for the combination therapy in advanced solid tumors have also been encouraging.

At the 2020 International Association for the Study of Lung Cancer (IASLC) North America Conference on Lung Cancer, researchers reported the Phase 1/2 clinical data for MK-1308A. The study primarily evaluated the safety and tolerability of MK-1308 in combination with Keytruda as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The results demonstrated that the combination therapy exhibited a favorable safety and efficacy profile with no unexpected toxicities, and showed promising antitumor activity. Specifically, the overall objective response rate (ORR) was 35.1%; the median progression-free survival (PFS) in the overall population was 6.1 months, with a 6-month PFS rate of 54%; the median overall survival (OS) in the overall population was 16.5 months, with a 12-month OS rate of 67%. These findings support the continued development of the MK-1308 and Keytruda combination therapy.

Screenshot source: Chinadrugtrials

In China, MK-1308A injection has twice received implied approval for clinical trials from the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration (NMPA), with intended indications for development including advanced solid tumors and hepatocellular carcinoma. According to the China Drug Clinical Trial Registry and Information Disclosure Platform, MSD is currently conducting a Phase 1/2, open-label, multi-arm, multicenter study of MK-1308 in combination with pembrolizumab in subjects with advanced solid tumors.

Note: The original text has been abridged.

References:

[1] Akeso's CTLA-4 Monoclonal Antibody Licensed to MSD for $200 Million Enters Phase III Clinical Trial. Retrieved June 16, 2021, from https://mp.weixin.qq.com/s/c2aHJtkWBFizb46KUaT8ow

[2]Perets P,Bar J,Rasco DW,et al.Safety and Efficacy of Quavonlimab,a Novel Anti-CTLA-4 Antibody (MK-1308),in Combination with Pembrolizumab in First-Line Advanced Non-Small Cell Lung Cancer[EB/OL].Ann Oncol,2020,S0923-7534(20)43175-8.

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