Does this month mark the beginning of a new era in cancer care?
Merck hasn’t had the best couple of years – the company’s revenues declined from $13.5 billion to $12.7 billion between 2010 and 2013 – but it’s been an amazing summer for its lead oncology candidate, pembrolizumab (also known as MK-3475). Pembrolizumab is a humanized programmed death receptor-1 (PD-1) antibody that blocks the PD-1 pathway, which is the very pathway that cancers activate in order to suppress the immune system. By blocking PD-1, pembrolizumab reactivates the immune system’s antitumor activity.
Merck’s candidate is part of a class of immuno-oncology drugs that allow the body’s own immune system to recognize and destroy cancer cells. And assuming that pembrolizumab is approved on or before its Prescription Drug User Fee Act (PDUFA) date of October 28, it will become the first-ever FDA-approved PD-1 antibody, ushering in a new and exciting era for cancer treatments.
A ‘benign therapy’
More than 25,000 people convened in Chicago for the annual American Society of Clinical Oncology (ASCO) meeting this past June. There, Merck unveiled data from the largest study to date of the effects of pembrolizumab monotherapy in patients with advanced melanoma.
Advanced melanoma is one of the most challenging cancers to treat, with a 10-year survival rate of less than 10%. In a phase 1b study of 411 patients with advanced melanoma, 34% of patients treated with pembrolizumab experienced a tumor response. The overall survival rate after one year of treatment was 69% for all patients, while the overall survival rate for treatment-naïve patients was 74%. Furthermore, the survival rate was 65% for patients who had been previously treated with Yervoy (ipilimumab), the most widely used treatment for advanced melanoma, and 88% of patients who responded to treatment had a sustained response.
Not only was there a durable response to treatment, but a refreshing lack of harmful side effects. A mere 4% of patients dropped out of the study due to adverse events. The dosing schedule in the trials was reasonable, with patients receiving 10 mg/kg every two or three weeks, or 2 mg/kg every three weeks.
Dr. Antoni Ribas, professor of hematology-oncology at the University of California at Los Angeles and a lead investigator in the trial, has referred to pembrolizumab as “one of the most benign therapies I have ever used.”
Robust clinical trials
Pembrolizumab is being studied in 17 clinical trials in over 4,000 patients. By the end of the year, the clinical trial program will expand to include 6,000 patients and a total of 24 clinical trials.
The goal here is to go beyond merely changing the prognostic outlook for melanoma patients -- Merck is hoping to shift the very treatment paradigm. With pembrolizumab, the company is striving for a 10-year survival rate among advanced melanoma patients in the 75% range.
Though the documented PDUFA date for pembrolizumab is October 28, informed onlookers are convinced that the approval will come through at some point in September. On May 14, pembroizumab was granted priority review by the FDA, and on July 1, Merck filed a submission for approval of pembrolizumab in the EU. Analysts are predicting blockbuster sales after the treatment receives approval, with projected sales of $30 billion by 2025.
More than melanoma
Merck initially chose to test pembrolizumab in patients with advanced melanoma precisely because the cancer is so difficult to treat. That was a good starting point -- but now there are numerous studies underway evaluating pembrolizumab for a variety of cancer. In oncology, combination therapy often yields the best outcomes. And with that understanding, Merck is collaborating with a number of partners to test various other cancer therapies in combination with pembrolizumab.
For instance, Pfizer and Merck are collaborating to study pembrolizumab combined with Pfizer’s small-molecule kinase inhibitor Xalkori (crizotinib) for the treatment of non-small cell lung cancer (NSCLC), which has a 10-year survival rate around 7% in patients with advanced disease and is the leading cause of cancer-related death worldwide. Pfizer and Merck are also collaborating to study the effect of pembrolizumab combined with Pfizer’s Inlyta (axitinib) in patients with renal cell carcinoma.
Separately, Merck is partnering with Advaxis to test the combination of pembrolizumab with Advaxis’ Listeria monocytogenes (Lm)-LLO immunotherapy. Researchers will evaluate this combo in men with previously treated, metastatic, castration-resistant prostate cancer. The goal: to combine two different approaches to priming the immune system in order to enhance the body’s anti-tumor response.
The future of cancer care
The evolution of cancer care has been built on a series of incremental breakthroughs and game-changing therapies, starting with the introduction of hormone therapy and radiation in the early 20th century and the subsequent advent of chemotherapy in the mid-20th century. According to the American Cancer Society, metastatic cancer was cured for the first time in 1956 using methotrexate.
Beyond these marquee events, there have been hundreds of hard-won breakthroughs that have shifted the treatment landscape and significantly reduced the death rate from certain cancers. And once it is approved, pembrolizumab will become an indelible part of this timeline.
- www.onclive.com Pembrolizumab Combination Study Planned in Prostate
- The Lancet Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial
- Merck Data on Merck’s Pembrolizumab from Largest Study to Date of Investigational Anti-PD-1 Antibody in Advanced Melanoma Highlighted at ASCO 2014
- Reuters Exclusive: U.S. approval of Merck cancer immunotherapy expected soon