Merck Launches Ninth Global Phase III Trial of SKB264 (MK-2870) in Squamous NSCLC, Benchmarking Against KEYNOTE-407
MSD
Pharmaceutical R&D and Manufacturer
On May 20, 2024, Merck & Co., Inc. initiated a Phase III global clinical trial (number MK-2870-023) to compare the use of Pembrolizumab alone versus Pembrolizumab combined with SKB264 as first-line maintenance therapy for patients with metastatic squamous non-small cell lung cancer. Patients enrolled in the trial will first receive combination treatment with Pembrolizumab, carboplatin, and taxane-class drugs. The total number of patients expected to be recruited is 851.
The design of the MK-2870-023 trial does not directly compare the efficacy of Pembrolizumab combined with SKB264 to Pembrolizumab monotherapy as a first-line treatment, but rather compares it against the results of the Keynote-407 trial.
Unlike the Keynote-407 trial, which continued with Pembrolizumab monotherapy after the fourth cycle, the MK-2870-023 trial opted for a combination therapy strategy of Pembrolizumab and SKB264 at the same stage.
About Keynote-407:
MSD conducted a global Phase III clinical trial named Keynote-407 to investigate the efficacy of Pembrolizumab in combination with carboplatin and taxane drugs (including paclitaxel and nab-paclitaxel), compared with placebo plus chemotherapy, for the treatment of patients with metastatic squamous non-small cell lung cancer.
In this study, a total of 559 patients participated, with 278 patients in the Pembrolizumab plus chemotherapy group and 281 patients in the placebo plus chemotherapy group.
Baseline Characteristics of Enrolled Patients
Median Overall Survival (mOS):The median overall survival (mOS) in the Pembrolizumab plus chemotherapy group reached 15.9 months, compared to 11.3 months in the chemotherapy-alone group. This indicates that the use of Pembrolizumab combined with chemotherapy significantly reduces the risk of death, with a hazard ratio (HR) of 0.64, meaning a 36% reduction in risk. Additionally, the 1-year survival rate was significantly higher in the combination therapy group at 65.2%, compared to 48.3% in the chemotherapy-only group.
Median Progression-Free Survival (mPFS):The median progression-free survival (mPFS) for Pembrolizumab combined with chemotherapy was 6.4 months, compared to 4.8 months for the group receiving chemotherapy alone. Furthermore, the use of Pembrolizumab in combination with chemotherapy significantly reduced the risk of disease progression or death, with a hazard ratio (HR) of 0.56, indicating a 44% reduction in risk.
Overall Response Rate (ORR):The overall response rate (ORR) in the Pembrolizumab plus chemotherapy group reached 57.8%, compared to 38.4% in the chemotherapy-alone group, demonstrating the significant advantage of combination therapy in enhancing treatment efficacy.
About SKB264/MK-2870/ Sacituzumab Tirumotecan/ Sac-TMT/Trastuzumab Deruxtecan
SKB264 is a TROP2-targeted ADC developed by Kelun-Biotech based on its OptiDC platform, with a Belotecan derivative as the payload and a DAR value of 8.
SKB264 Structure
As of May 20, 2024, MSD Kelun-Biotech has registered 9 global Phase III clinical trials and 5 Phase III clinical trials in China.
MSD/Kelun-Biotech SKB264/MK-2870 International Phase III Clinical Trial:
MSD/Kelun-Biotech SKB264/MK-2870 Phase III Clinical Trial in China:
References:
Pembrolizumab plus Chemotherapy for Squamous Non–Small-Cell Lung Cancer. New England Journal of Medicine (2018), 379(21), 2040-2051.
