Merck Halts Two Phase III Trials of Keytruda Due to Lack of Efficacy and Unfavorable Risk-Benefit Profile

Aug 30, 2024 08:57 CST Updated 08:57

MSD

Pharmaceutical R&D and Manufacturer

On August 29, 2024, local time, Merck & Co., Inc. announced the termination of two Phase III clinical trials, KEYNOTE-867 and KEYNOTE-630, due to unsatisfactory clinical data.

KEYNOTE-867 Study Aims to Explore the Efficacy and Safety of Keytruda (K Drug) in Combination with Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Early-Stage Non-Small Cell Lung Cancer, with Approximately 436 Patients Enrolled.

For inoperable early-stage non-small cell lung cancer, SBRT is currently the best treatment option.

KEYNOTE-630 Study: Exploring the Efficacy and Safety of K Drug as Adjuvant Therapy for High-Risk Locally Advanced Cutaneous Squamous Cell Carcinoma (cSCC) Patients After Surgery and Radiation Therapy, with Approximately 430 Enrolled Patients.

According to the official website, the termination of the two studies was based on the recommendation of the Independent Data Monitoring Committee (DMC).

The interim analysis of KEYNOTE-867 showed that, compared with placebo, the combination of K drug + SBRT did not demonstrate significant differences in the primary endpoint EFS and key secondary endpoint OS.

Moreover, in terms of safety, the combination of K drug + SBRT had a higher incidence of adverse events compared to the placebo group, including patient deaths.

In view of this, MSD believes that the risk-benefit ratio of the combination therapy does not support continuing the trial.

KEYNOTE-630 was the same, failing to reach the primary clinical endpoint (recurrence-free survival, RFS). Although the critical secondary endpoint OS has not been concluded, MSD stated that based on the data from the pre-specified analysis, it was deemed unnecessary.

In fact, just this year, MSD has terminated several Phase III clinical trials of Keytruda, including KEYLYNK-006, which combined Keytruda with the PARP inhibitor olaparib; and two studies combining Keytruda with the TIGIT antibody vibostolimab, KeyVibe-008 and KeyVibe-010.

With the U.S. patent for Keytruda set to expire in 2028, MSD has chosen a different path from AbbVie's "patent thicket" strategy for Humira, opting instead to expand the indications for Keytruda in multiple dimensions.

Currently, MSD is studying the role of K drug in combination with various treatment regimens across different tumor types in more than 1,600 clinical trials, including its combined use with oncolytic viruses, ADCs, and mRNA cancer vaccines.

According to the Informa database, there are 146 Phase II/III or Phase III studies being conducted for Keytruda alone.

Although K drug has experienced multiple rounds of failures since its launch in 2014. The cola combination with more failures than successes, the failure of combination with PARP, the failure of combination with TIGIT, the failure of combination with SBRT, and the failure as adjuvant therapy…

ButMSD continues to make trials and errors,To date, K drug has been approved for approximately 40 indications in the United States, covering multiple types of cancer such as melanoma, lung cancer, liver cancer, and head and neck cancer. It has also been approved for more than ten indications in China.

Such efforts have successfully propelled Keytruda to the top position of "the best-selling drug."Sales reached $25 billion in 2023. Maintaining double-digit year-on-year growth for a long time is the reward for continuous trial and error.

In the first half of 2024, the sales of K drug reached a new high of 14.2 billion US dollars. This is an enviable achievement for many PD-1/PD-L1 drugs.

The once-famous OK大战 has quietly come to an end, and nowWhether it is Biotech or Pharma, anti-tumor drugs are often benchmarked against K drug.

In May this year, Akeso announced that data from the HARMONi-2 (AK112-303) study conducted in China showed that, in the intent-to-treat population (ITT), the Ivonescimab group significantly extended progression-free survival (PFS) compared to the Keytruda group, with a hazard ratio (HR) significantly better than expected.

Affected by the news, the intra-day share price of Akeso once surged over 87%, inversely confirming the recognition of Keytruda by both the pharmaceutical industry and the investment community.

Summary

According to incomplete statistics, K drug had at least 13 failed studies in 2023. Similarly, K drug also successfully ushered in the IO+ADC era through its combination with nectin-4 ADC, vindeotuximab.

For Keytruda, MSD should have a dedicated set of evaluation criteria, including how much to spend on acquiring assets for combination use; whether to enter Phase III trials, and at what point in Phase III can the trial be terminated.

This is exclusively for K medicine.TheSuspension method.

Cover image source: 123rf

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