Merck & Co. on Monday presented promising Phase Ib study data at the ASCO annual meeting for the experimental anti-PD-1 antibody pembrolizumab, also known as MK-3475, in patients with advanced melanoma and also those with PD-L1-positive, advanced non-small-cell lung cancer (NSCLC). Roger M. Perlmutter, president of Merck Research Laboratories, remarked "while we await further confirmation through controlled clinical trials, the survival rates seen with pembrolizumab therapy, including in patients with advanced disease who have failed other therapies, support the use of immune manipulation in cancer care."
The results come from the KEYNOTE-001 trial, which included 411 patients with advanced melanoma, 77 percent of whom had received at least one prior systemic therapy. Merck noted that following treatment with pembrolizumab, the estimated overall survival (OS) rate at one year was 69 percent across all patients, including 74 percent in those previously treated with Bristol-Myers Squibb's Yervoy (ipilimumab) and 65 percent in patients who had progressive disease on or following Yervoy. In addition, at 18 months, the estimated OS was 62 percent. Merck indicated that median OS has not been reached, with some patients receiving treatment with pembrolizumab for more than two years.
Overall, the company said that 34 percent of patients had tumour shrinkage, including 40 percent not treated with Yervoy and 28 percent whose cancer progressed despite treatment with Bristol-Myers Squibb's therapy. According to Merck, the most common immune-related adverse events included thyroid problems, while 4 percent of patients stopped treatment due to side effects. Antoni Ribas, the study's lead investigator, remarked "in general, this is probably the safest drug I have ever used in metastatic melanoma patients."
The KEYNOTE-001 trial also included patients with stage IV NSCLC who had no prior systemic therapy and whose tumours were assessed as positive for PD-L1 expression. Merck noted that in the study cohort, 78 percent of evaluable patients were determined to be PD-L1 positive as measured by the company's immunohistochemistry trial assay. The drugmaker indicated that the data are the first to be presented investigating pembrolizumab as initial therapy in patients with PD-L1-positive, advanced NSCLC.
Results demonstrated that the objective response rate was 47 percent by investigator-assessed, immune-related response criteria and 26 percent by centrally evaluated RECIST v1.1. Merck vice president of oncology Alise Reicin, who estimated that around 70 percent of patients with advanced NSCLC have tumours that express PD-L1, said that two different methods were used because standard measures can underestimate the impact of drugs that work by targeting the immune system.
Merck added that in evaluable patients who had measurable disease with one post baseline scan, 80 percent demonstrated tumour shrinkage as measured by centrally evaluated RECIST criteria. The drugmaker noted that the median duration of response has not been reached, with some patients continuing on treatment with pembrolizumab for at least one year. "As clinical experience with pembrolizumab grows...we are seeing durable responses across multiple lines of therapy, including in the first-line treatment setting," commented Roy Baynes, senior vice president, global clinical development at Merck Research Laboratories. "Exploring the clinical utility of tumour characteristics, such as expression of PD-L1 as a potential marker for patient selection or study enrichment, is an important part of our research programme in this disease," Baynes said.
In January, Merck initiated a rolling submission of a filing with the FDA for pembrolizumab in advanced melanoma, with the agency expected to reach a decision by October 28. The drug was awarded FDA breakthrough therapy status for advanced melanoma last year. Reicin declined to comment on when the drugmaker would seek clearance in the lung cancer indication, but noted that the company plans to launch a Phase III study in September comparing the drug to chemotherapy in previously-untreated patients with PD-L1 positive, advanced NSCLC. Morningstar estimates that peak annual sales of pembrolizumab could reach $6 billion.
Other companies developing anti-PD-1 and anti-PDL-1 drugs include AstraZeneca, Roche and Bristol-Myers Squibb, with the latter reporting Monday positive results from a Phase Ib study of its experimental therapy nivolumab in patients with advanced melanoma.
For related analysis, see ViewPoints: New data indicates key role for biomarkers in immuno-oncology development race, FirstWord Lists: A revolution in cancer – a launch calendar for key immuno-oncology indications and Physician Views Poll Results: First-to-market status for Merck & Co.'s MK-3475 in melanoma could open substantial opportunity for off-label front-line usage.
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