Merck’s Drug Keytruda Shows ‘Encouraging’ Results in Mesothelioma Clinical Trial

Regardless of the name used – Keytruda, MK-3475, or pembrolizumab – Merck’s immunotherapy drug may be the lifeline patients around the world have been seeking. In a clinical trial, Keytruda was found to be effective in controlling mesothelioma tumors in three-fourths of patients.

Preliminary results of the Phase IB KEYNOTE-028 clinical trial offered to cancer patients with 20 different tumor types, including the asbestos-caused cancer, were announced at the 2015 American Association for Cancer Research Annual Meeting held April 18-22 in Philadelphia. Evan W. Alley, MD, PhD, and co-director of the Penn Mesothelioma and Pleural Program at the University of Pennsylvania, discussed the results of the trial with OncLive.

Dr. Alley reported that the 25 patients enrolled in the trial, all who had previously received standard chemotherapy treatment but still had tumor growth, received the drug every two weeks. Seven patients had partial response (a decrease in tumors size) and 12 patients had stable disease (no tumor growth or shrinkage). The final results show an overall disease control rate of 76%.

“The survival for this patient population in general, for mesothelioma, is about 13 months – so it’s a bad disease,” said Dr. Alley. And when patients undergo second round chemotherapy, which has just a 10 percent response rate and for which there is no standard of care, Dr. Alley said, “response rates are very poor.”

“The fact that we saw 28% response, in this small study, and the additional stable disease rate, was quite encouraging,” said Dr. Alley.

Cancer is adept at evading detection by T-cells, which hunt down and kill intruder cells. By disrupting certain immune system signaling pathways, cancer can effectively deactivate T-cells and proliferate freely.

PD-L1, or programmed death-ligand 1, is a protein that has been shown to play a role in suppressing the immune system during cancer and other diseases. According to Merck, Keytruda blocks the interaction between PD-1 (a protein on the surface of T-cells) and its ligands, PD-L1 and PD-L2 (found on the surface of cancer cells), enabling activation of T-cells and an immune response to cancer.

In Sept. 2014, the U.S. Food and Drug Administration granted accelerated approval to Keytruda (pembrolizumab) for treatment of patients with advanced or unresectable melanoma.”

Australian Survivor Lou Williams Starts Therapy With Keytruda; UK Meso Warrior Mavis Nye Sees Success in Clinical Trial

Lou Williams, a double mesothelioma survivor (she has both pleural and peritoneal mesothelioma) of over 12 years, celebrated her 60th birthday on April 20. In her April 4 blog, though, Lou painted a bleak future as she struggled with weight loss and growing tumors. Without some intervention in her treatment, she wrote, “I will die probably in a few weeks – simple as that.”

However, Lou has been offered a ray of hope, announcing in her blog, Asbestos-Living with Mesothelioma in Australia Louise (Lou) Williams, that she is now taking Keytruda. Lou has gotten this far with four surgeries, 36 rounds of chemotherapy, countless days in the hospital, and most recently, even more chemotherapy and radiation. With Keytruda, her oncologist told her “hopefully” she could see 18 months or more of life.

“Thursday 9 April was a turning point in my progression of this cancer to being handed a life saving drug that will hopefully stimulate my immune system, shrink tumor progression and give me more quality of life and lots more living to do!” she said in her blog.

Keytruda is a new drug in Australia and the Therapeutic Goods Administration, the equivalent to the U.S. Food and Drug Administration, has registered the drug for initial mesothelioma treatment of patients with advanced melanoma. In the UK, meanwhile, Keytruda, referred to as MK-3475, is still in Phase I clinical trials.

Mavis Nye, a five year survivor of mesothelioma and Keytruda clinical trial patient at the Royal Marsden in the UK, has seen “brilliant results” with the drug. Mavis told Mesothelioma Help in September that her tumors were shrinking and, “I’m feeling very well as my immune system has been turned back on by the drug.”

Mavis reports on her blog, Living with Mesothelioma, that she now has some fellow mesothelioma warriors to share in her experience. “I at long last have someone I can compare how I feel with as Lou and I message each other,” she wrote on April 13.

When asked in an email by Mesothelioma Help what her personal hopes are for the drug, Mavis said, “I have so much shrinkage, my scan on May 19th could show more than 60%-70% at No 23 Cycle. My wish is for the shrinkage to take me back to thickenings as is happening to some of my smaller tumours.”

And the best may be yet to come for her. The researchers heading the trial are closely watching Mavis’ tumor shrinkage as they assess her response. “They are waiting to see just how much shrinkage I will get as I haven’t reached all the shrinkage that I think could happen,” she told Mesothelioma Help.

The success Mavis and other patients have seen, however, should be tempered by the reality that mesothelioma—diagnosed in approximately 3,000 Americans, 2,500 Brits and 600 Australians each year—remains an extremely stubborn cancer with no cure.

In addition to medical breakthroughs, it is important to focus attention on legislative solutions that outlaw asbestos. Unlike the UK and Australia, the United States has not banned asbestos, which causes an estimated 10,000 deaths in this country each year.

Image: Copyright © 2009-2015 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A. All rights reserved.

Sources:

• Dr. Evan Alley on KEYNOTE-028 Trial Results in Mesothelioma
  http://www.onclive.com/conference-coverage/aacr-2015/dr-evan-alley-on-keynote-028-trial-results-in-mesothelioma
• Phase IB KEYNOTE-028 clinical trial offered to cancer patients with 20 different tumor types
  https://clinicaltrials.gov/ct2/show/study/NCT02054806?term=keynote-28&rank=1#locn
• Mavis Nye Hopes to Pave the Way for Patients as the First UK Patient in Clinical Trial
  https://www.mesotheliomahelp.org/mavis-nye-way-mesothelioma-patients-uk-clinical-trial-40939/
• Pembrolizumab in Treating Patients With Malignant Mesothelioma
  https://clinicaltrials.gov/ct2/show/NCT02399371?term=keytruda+mesothelioma&rank=1
• Pembrolizumab drug halts tumor growth in 76% of patients with pleural mesothelioma
  http://www.news-medical.net/news/20150420/Pembrolizumab-drug-halts-tumor-growth-in-7625-of-patients-with-pleural-mesothelioma.aspx
• Ron Walker’s $150,000 cancer drug Keytruda approved for melanoma patients
  http://www.smh.com.au/national/health/ron-walkers-150000-cancer-drug-keytruda-approved-for-melanoma-patients-20150420-1more8.html
• Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28)
  https://clinicaltrials.gov/ct2/show/study/NCT02054806?term=keynote-28&rank=1#locn
• Asbestos-Living with Mesothelioma in Australia Louise (Lou) Williams
  https://asbestosaustralia.blogspot.com/2015/04/lou-is-back-on-wonder-drug-keytruda.html