Merck & Co’s anti-PD-1 therapy Keytruda dazzled in its pivotal Phase III KEYNOTE-407 trial.
Merck & Co’s anti-PD-1 therapy Keytruda dazzled in its pivotal Phase III KEYNOTE-407 trial in combination with carboplatin-paclitaxel or nab-paclitaxel as first-line treatment for metastatic squamous non-small cell lung cancer (sNSCLC).
The combination met dual primary endpoints—overall survival (OS) and progression-free survival (PFS), and in an interim analysis by the independent Data Monitoring Committee (DMC), the combo treatment had significantly longer OS and PFS than just chemotherapy. The safety profile was consistent with previous studies in lung cancer.
Merck submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA). The data will also be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in early June.
“As first-line treatment, Keytruda in combination with traditional chemotherapy has now demonstrated an improved survival benefit, compared to chemotherapy alone, in metastatic lung cancer patients with squamous histology,” said Roger Perlmutter, president of Merck Research Laboratories, in a statement. “We look forward to presenting the overall survival and progression-free survival findings from KEYNOTE-407 at the 2018 ASCO Annual Meeting, and are grateful to the patients and ivnestigators for their important contributions to this pivotal study.”
KEYNOTE-407 is a randomized, double-blind, placebo-controlled, Phase III trial. It is looking at Keytruda in combination with carboplatin-paclitaxel or nab-paclitaxel compared to carboplatin-paclitaxel or nab-paclitaxel alone. It evaluated 560 untreated patients with metastatic squamous NSCLC. Patients had no previous systemic therapy or advanced disease.
Keytruda is involved in more than 750 clinical trials in a variety of cancers and treatment settings. So far it is approved to treat melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, microsatellite instability-high (MSI-H) cancer, and gastric cancer.
Earlier data from the trial involving 204 patients had an overall response rate of 58.4 percent in the combination compared to 35 percent on chemotherapy alone.
Roche will also be presenting data at ASCO from its Phase III IMpower150 study of Tecentriq (atezolizumab) and Avastin (bevacizumab) plus carboplatin and paclitaxel (chemotherapy) for the first-line treatment of chemotherapy-naïve patients with metastatic non-squamous NSCLC. In an early analysis, Sandra Horning, Roche’s chief medical officer and head of Global Product Development, stated, “The IMpower150 study results showed a significant survival benefit, adding to the clinical evidence supporting the combination of Tecentriq and Avastin as an initial treatment for metastatic non-squamous non-small cell lung cancer. An overall survival benefit was also observed in key populations such as people with EGFR- and ALK-positive mutations and those with liver metastases.”
At this point, Merck’s Keytruda is the only immunotherapy approved in the U.S. for lung cancer patients who have not received prior treatment. Squamous cell NSCLC makes up about 30 percent of all lung cancers. Patients diagnosed with squamous cell lung cancer generally have a poor prognosis because it is usually diagnosed after it has spread.
All the news may not be good, however. The FDA recently warned physicians, trial investigators and the public last Friday that Merck’s Keytruda and Roche’s Tecentriq showed some warning signs in recent trials in bladder cancer. Oversight committees observed in both studies that patients with low PD-L1 biomarker levels treated with the immunotherapies had decreasing survival chances compared to those who took platinum chemotherapy. Both drugs have conditional approval for certain bladder cancers in treatment-naïve patients. Regulators are asking doctors and patients to report any side effects related to either drug. They’re also encouraging healthcare providers to adhere to the drugs’ labels when prescribing.
