Merck’s KEYTRUDA Fails in Early-Stage Lung and Skin Cancer Trials, Ends Two Phase 3 Studies

Merck & Co.’s attempt to advance KEYTRUDA (pembrolizumab) into early lung cancer treatment has failed, as has its effort to expand into early-stage skin cancer. On August 29th, the company announced its decision to halt the Phase 3 KEYNOTE-867 trial for KEYTRUDA in inoperable stage 1 or 2 non-small cell lung cancer (NSCLC). Additionally, Merck has chosen to end the KEYNOTE-630 trial Phase 3 trial aimed at early-stage skin cancer.

KEYTRUDA-Radiation Combo Fails to Improve Early-Stage Lung Cancer Outcomes

During a planned interim analysis, KEYTRUDA’s addition to radiation therapy failed to improve patients’ risk of disease progression or death, Merck reported. Moreover, the combination led to higher rates of adverse events, including fatalities. The study compared this pairing against stereotactic body radiotherapy alone.

After reviewing the data, an independent data monitoring committee concluded that the benefit-risk profile of the KEYTRUDA-radiotherapy regimen did not justify continuing the trial, according to Merck. The trial’s termination reflects the therapy’s ineffectiveness in this early-stage setting.

Despite this setback, KEYTRUDA remains the first-line standard of care in metastatic NSCLC. In October, the PD-1 inhibitor also secured an FDA approval for continuous treatment before and after surgery in resectable NSCLC. However, Merck faces challenges in further enhancing KEYTRUDA for metastatic NSCLC, especially with potential competition from a PD-1/VEGF bispecific antibody by Akeso and Summit Therapeutics.

Merck Faces Further Setbacks in Lung Cancer Trials

In two consecutive failures, Merck found that using its AstraZeneca-partnered Lynparza during the maintenance treatment of newly diagnosed metastatic NSCLC did not succeed. The drug failed across both non-squamous and squamous histologies in two separate Phase 3 studies.

Additionally, a combination of KEYTRUDA and Merck’s investigational anti-TIGIT antibody vibostolimab proved less effective than the chemotherapy docetaxel in a phase 2 trial for previously treated metastatic NSCLC. Despite this, Merck continues with three Phase 3 trials of MK-7684A, a fixed-dose combo of KEYTRUDA and vibostolimab, in various NSCLC settings.

Following Merck’s latest setback, the search for an effective PD-1/L1 inhibitor in stage 1 or 2 unresected NSCLC continues for at least one other company. AstraZeneca is conducting the Phase 3 PACIFIC-4 trial, testing its PD-L1 inhibitor Imfinzi alongside radiotherapy in a design similar to Merck’s KEYNOTE-867 trial. AstraZeneca’s study, which started three months earlier than Merck’s, includes a separate cohort examining Tagrisso after radiotherapy in EGFR-mutant tumors.

Merck Halts KEYTRUDA Trial for High-Risk Skin Cancer

In another setback for KEYTRUDA, Merck announced Thursday that it is discontinuing the phase 3 KEYNOTE-630 trial. The study aimed to evaluate KEYTRUDA as an adjuvant treatment for patients with high-risk locally advanced cutaneous squamous cell carcinoma (cSCC) following surgery and radiation.

An independent data monitoring committee recommended stopping the trial due to futility. KEYTRUDA failed to meet the primary endpoint of recurrence-free survival, showing no advantage over placebo in preventing disease recurrence or death. Additionally, KEYTRUDA did not improve patients’ life expectancy, although overall survival was not formally tested due to the primary endpoint failure. Despite this setback, KEYTRUDA remains approved for recurrent or metastatic cSCC and for locally advanced cSCC that cannot be treated with surgery or radiation.

These results indicate that while KEYTRUDA has achieved success in many cancer treatments, its effectiveness in certain specific cases still requires further research and validation. Merck stated that they will continue to analyze the data and share the findings with the scientific community and regulatory bodies.

Author

Bernice Lottering