Cancer Immunotherapy on the Cusp

Editor’s note: Immunotherapy is a type of cancer treatment that uses a patient’s own immune system to fight cancer. Immunotherapies work in multiple types of cancer, but they have been particularly successful in treating melanoma. This article gives a good overview of the current state of immunotherapy research.

“Glass crystals with thread-like filaments floating inside sit in the offices of two prominent immunologists. The clear blocks encase models of the structure of PD-1/PD-L1, a receptor-ligand pair that rides on the surface of cells, ready to rein in the immune system after its work attacking invaders is done.

“PD-1 looms large in the growing field of cancer immunotherapy, which is why one model appears on Gordon Freeman’s desk in the Dana-Farber Cancer Institute and the other in Arlene Sharpe’s office at Harvard Medical School. Their basic science discoveries about how cancer cells hijack PD-1 to turn off the immune system are being translated into therapies that they hope and believe can change cancer treatment. After 15 years, drugs developed by several pharmaceutical companies based on the scientists’ work are awaiting approval by the U.S. Food and Drug Administration.

” ‘It’s coming,’ Freeman, HMS associate professor of medicine at Dana-Farber, said this summer, anticipating FDA action.”


FDA Approves Keytruda for Advanced Melanoma

Editor’s note: Before a drug can be widely prescribed in the U.S., it must first be tested in humans and then approved by the U.S. Food and Drug Administration (FDA). Today, the FDA approved a new drug for treating melanoma. The drug is called Keytruda (pembrolizumab). It is for people with melanoma that is advanced or unresectable (can’t be removed by a surgeon) and is not responding well to other drugs. Keytruda is an “anti-PD-1″ immunotherapy drug that boosts a patient’s own immune system to fight cancer. It works by targeting an immune system molecule called PD-1 that can keep the immune system from attacking tumors. It is now the first anti-PD-1 drug to be approved.

“The U.S. Food and Drug Administration today granted accelerated approval to Keytruda (pembrolizumab) for treatment of patients with advanced or unresectable melanoma who are no longer responding to other drugs.

“Melanoma, which accounts for approximately 5 percent of all new cancers in the United States, occurs when cancer cells form in skin cells that make the pigment responsible for color in the skin. According to the National Cancer Institute, an estimated 76,100 Americans will be diagnosed with melanoma and 9,710 will die from the disease this year.

“Keytruda is the first approved drug that blocks a cellular pathway known as PD-1, which restricts the body’s immune system from attacking melanoma cells. Keytruda is intended for use following treatment with ipilimumab, a type of immunotherapy. For melanoma patients whose tumors express a gene mutation called BRAF V600, Keytruda is intended for use after treatment with ipilimumab and a BRAF inhibitor, a therapy that blocks activity of BRAF gene mutations.”


Pfizer to Test Xalkori Lung Cancer Drug with Merck Immunotherapy

Editor’s note: This article is about two big drug companies that are teaming up to see if their non-small cell lung cancer drugs work even better when combined. The two drugs are called pembrolizumab and crizotinib (aka Xalkori). Pembrolizumab is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. Crizotinib is a targeted therapy that is meant to treat people whose tumors have mutations in the ALK gene. To test the combo, the companies are organizing a clinical trial—a research study with volunteer patients. The clinical trial will not begin until 2015.

“Pfizer Inc said Tuesday it will test its Xalkori lung cancer drug with Merck & Co’s experimental immunotherapy pembrolizumab, in hopes the combination will improve the outcomes for patients taking the approved Pfizer therapy.

“The largest U.S. drugmakers said the combination study will begin in 2015 and be conducted by Pfizer. Financial terms of the deal were not disclosed.

“Xalkori, which has annual sales of $400 million and is also known by its chemical name, crizotinib, was approved in 2011 for lung cancer patients who have a specific mutation in the so-called ALK gene, as determined by an approved diagnostic test.

“The mutation occurs in a small percentage of patients with non small cell lung cancer, the most common form of lung cancer. It makes them good candidates for treatment with Xalkori, a targeted drug that can help shrink or slow tumor growth for these patients.

“Pembrolizumab works by removing the brakes from the immune system, allowing it to detect and destroy cancer cells.”

 


Advaxis, Merck to Test Immune Therapies Against Prostate Cancer

Editor’s note: This article is about two big drug companies that are teaming up to see if their prostate cancer drugs work even better when combined. The two drugs are called pembrolizumab and ADXS-PSA. Both drugs are immunotherapies, meaning that they boost a patient’s own immune system to fight cancer. To test the combo, the companies are organizing a clinical trial—a research study with volunteer patients. The clinical trial will not begin until 2015.

“Advaxis Inc on Monday said it will test an experimental immuno-oncology drug in combination with a high-profile immunotherapy from Merck & Co Inc as a treatment for patients with advanced prostate cancer.

“The tiny U.S. biotechnology company, in its second cancer collaboration with a large drugmaker in the past month, said it would evaluate the use of its ADXS-PSA as a standalone treatment and also study it in combination with Merck’s pembrolizumab in the Phase I/Phase II trial.

“Merck’s drug is a member of an exciting new class of medicines called “PD-1 inhibitors” that work by blocking the PD-1 protein, thereby taking the brakes off immune system cells and prodding them to attack tumors…

“By using different approaches, the drugmakers hope the two drugs have a better chance of knocking down the prostate cancer than either could achieve on its own.”


Exclusive: U.S. Approval of Merck Cancer Immunotherapy Expected Soon

Editor’s note: Before a new cancer drug can be prescribed by oncologists in the U.S., it must be approved by the U.S. Food and Drug Administration (FDA). The FDA may soon approve a new melanoma drug called pembrolizumab. Pembrolizumab is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. It may be particularly helpful for people whose melanoma does not respond to treatment with another immunotherapy drug called ipilimumab (Yervoy).

“U.S. regulators are likely to approve Merck & Co’s highly anticipated immuno-oncology drug, pembrolizumab, as a treatment for melanoma well ahead of a late October deadline, according to three sources familiar with the situation.

“If approved by the Food and Drug Administration, the drug would be the first in a promising new class designed to help the body’s own immune system fend off cancer by blocking a protein known as Programmed Death receptor (PD-1), or a related target known as PD-L1, used by tumors to evade disease-fighting cells.

“Companies including Bristol-Myers Squibb, Roche Holding AG and AstraZeneca Plc are racing to develop similar treatments for a variety of cancers. Some analysts expect the new class could generate more than $30 billion in annual sales worldwide by 2025.”


Anti–PD-1 Antibody Pembrolizumab Shows Activity and Good Tolerability in Ipilimumab-Refractory Advanced Melanoma

The gist: Some people with melanoma who do not respond to treatment with ipilimumab (Yervoy) might benefit from immunotherapy drugs, which activate a patient’s own immune system to fight cancer. Researchers are testing an “anti-PD-1” immunotherapy drug called pembrolizumab in a clinical trial with volunteer patients. The results suggest that pembrolizumab might be a good treatment for advanced melanoma patients who have few other options. Learn more about immunotherapy treatments for melanoma at our Need to Know blog.

“As reported in The Lancet by Robert et al, the anti–programmed death receptor-1 (PD-1) antibody pembrolizumab produced responses and was well tolerated at two dose levels in an expansion cohort of a phase I trial in patients with ipilimumab (Yervoy)-refractory advanced melanoma.

“In this open-label multicenter trial, 173 adult patients with advanced melanoma progressing after at least two ipilimumab doses were randomly assigned to receive intravenous pembrolizumab at 2 mg/kg (n = 89) or 10 mg/kg (n = 84) every 3 weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was overall response rate on independent central review…

“The investigators concluded, ‘The results suggest that pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options.’ ”


ASCO 2014: Highlights for People Dealing with Melanoma


Every year, new cancer treatment insights are shared at the American Society of Clinical Oncology (ASCO) Annual Meeting. Here are some of the most notable recent developments in melanoma treatment, gleaned from researchers’ presentations at ASCO last month: Continue reading…


ASCO: Targeting PD-1 Works in Advanced Melanoma

“Two studies indicate that using investigative immunotherapy drugs improves survival and response in patients with metastatic melanoma, researchers said here.

“In one study, the agent pembrolizumab (MK-3475) which targets the programmed death (PD-1) pathway produced a 1-year 69% survival rate, said Antoni Ribas, MD, PhD, professor of medicine at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles.

“In a second study reported in a press conference at the annual meeting of the American Society of Clinical Oncology, Mario Sznol, MD, professor of medicine at the Yale Cancer Center, demonstrated that a combination of the investigative PD-1 inhibitor nivolumab in combination with another targeted agent ipilimumab (Yervoy) produced a 1-year survival rate of 85% and 2-year survival rate of 79% for advanced melanoma patients.”

Editor’s note: Immunotherapy drugs boost a patient’s own immune system to fight cancer. Promising research into new immunotherapy drugs for melanoma was recently presented at the American Society of Clinical Oncology (ASCO) Annual Meeting. Two treatments that received special attention were MK-3475 (aka pembrolizumab) and a combination of the drugs ipilimumab (Yervoy) and nivolumab.