Merck, known as MSD outside the United States and Canada, announced new data from the company’s large ongoing Phase 1b study (KEYNOTE-001) evaluating pembrolizumab (MK-3475), Merck’s investigational anti-PD-1 antibody, as a single agent (monotherapy) in 411 patients with advanced melanoma. Following treatment with pembrolizumab, the estimated overall survival (OS) rate at one year was 69% across all patients studied, including 74% in patients without prior ipilimumab therapy (current standard therapy) and 65% in patients who had progressive disease on or following ipilimumab. At 18 months, the estimated OS was 62%. The median OS has not been reached, with some patients receiving treatment with pembrolizumab as monotherapy for more than two years.

 

These new data will be presented in an oral session by Dr. Antoni Ribas, professor, Hematology/Oncology and Surgery, and director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO 2014) in Chicago.

 

“The data presented [Monday] provide further evidence of durable anti-tumor activity stimulated by pembrolizumab as a single agent in patients suffering from malignant melanoma,” said Dr. Roger Perlmutter, president, Merck Research Laboratories. “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.”

 

 

These data from 411 patients with advanced melanoma enrolled in multiple cohorts from KEYNOTE-001, the largest Phase 1b study to date of an anti-PD-1 antibody, will be highlighted as part of the ASCO 2014 Press Program. KEYNOTE-001 involved seven advanced melanoma cohorts including patients with varying stages of disease and prior lines of therapy. At baseline, 56% of patients had the most advanced stage of disease (M1c) (n=232) and 77% of patients had received at least one prior systemic therapy (n=316). Interim data from a single cohort of 135 patients from KEYNOTE-001 were first presented at ASCO 2013 and published concurrently in the New England Journal of Medicine. More recently, updated findings from this cohort were reported at the 10th International Congress of the Society for Melanoma Research.

 

At the time of analysis, 88% of reported responses in evaluable patients were ongoing and the median duration of response, by RECIST criteria, had not been reached. The median progression-free survival (PFS), by RECIST criteria, was 5.5 months overall (95% CI, 3.8-6.2), including 5.6 months in patients with no prior ipilimumab therapy (95% CI, 3.7-11) and 5.4 months in patients who had progressive disease on or following ipilimumab therapy (95% CI, 3.2-5.6). Anti-tumor activity was observed across all doses studied, regardless of the type and number of previous treatments (including prior ipilimumab therapy), performance status, Lactate Dehydrogenase (LDH) levels, BRAF mutation status, tumor size at baseline, and anatomical site of metastatic disease. An analysis of patient subgroups indicates that lower tumor burden at baseline is a strong predictor of response to pembrolizumab.

 

In patients with measurable disease at baseline who had at least one treatment scan, 72% showed tumor shrinkage, including 39% who had tumor shrinkage of greater than 50% by RECIST criteria. Based on irRC (central review), 64% of patients showed tumor shrinkage, including 31% who showed tumor shrinkage of greater than 80%.

 

The incidence of adverse events was consistent with previously reported data for pembrolizumab. The most common investigator-assessed, treatment-related adverse events were grade 1/2 and included fatigue, pruritus, rash, diarrhea and arthralgia, nausea, vitiligo, asthenia and cough. The most common immune-related adverse events included hypothyroidism and hyperthyroidism. Twelve treatment-related cases of pneumonitis were reported including one grade 3/4 event. The most common grade 3/4 treatment-related adverse event reported was fatigue. Overall, 17 patients discontinued treatment due to investigator assessed, treatment-related adverse events. No treatment-related deaths were reported.

 

Date: June 2, 2014

Source: Merck