Immune System-Activating Drugs in Combination Treatments May Be Next Big Thing for Melanoma


Among solid tumors, the curative potential of immunotherapies has been explored most in melanoma. One reason for this is that melanoma tumors often contain so-called immune infiltrates—patches of T cells, the killer cells of the immune system. It seems that these fighter cells arrive at the ‘battlefield’ to target tumor cells for killing, but instead become ‘frozen,’ unable to attack.  How to activate the tumor-killing potential of T cells has been an area of intense and fruitful research, leading to the development of several immunotherapy drugs. Continue reading…


UPDATE 1-Novartis Works with Bristol-Myers Squibb to Test Lung Cancer Drugs

The gist: Combining existing drugs can sometimes result in new, more effective cancer treatments. As we posted on our Need to Know blog today, lung cancer researchers are testing drug combinations that involve immunotherapies—treatments that boost the immune system to fight cancer. Now, two drug companies have announced that they will be testing combinations of their lung cancer drugs. An immunotherapy drug called Opdivo will be combined with targeted drugs. The combinations will be tested in clinical trials with volunteer patients who have late-stage non-small cell lung cancer (NSCLC). It is hoped that the combinations will work better than any of the drugs alone.

“Swiss pharma group Novartis AG said on Monday it would work with Bristol-Myers Squibb Co to test the U.S. drugmaker’s immuno-oncology drug Opdivo in combination with three of its own experimental lung cancer drugs.

“The clinical collaboration will help Novartis advance its efforts in the field of immunotherapy, one of the hottest areas in biotech right now, following the acquisition of CoStim Pharmaceuticals Inc this year, the drugmaker said.

“Novartis currently lags rivals such as Roche, Merck , AstraZeneca and Bristol-Myers in the race to develop immunotherapies – drugs that fight cancer by harnessing the body’s immune system.

“The two companies will test the combination of three molecularly targeted compounds with Bristol-Myers’ investigational PD-1 immune checkpoint inhibitor Opdivo (nivolumab) in phase I and II studies, Novartis said, adding it would conduct both studies.

” ‘Preclinical data suggests that combining molecularly targeted agents with immunotherapies such as nivolumab may have synergistic effects and lead to better outcomes for patients,’ Alessandro Riva, global head of Novartis oncology development and medical affairs, said in the statement.”


ESMO 2014: Lung Cancer Vaccine Fails to Improve Survival in Surgically Resected Non–Small Cell Lung Cancer

The gist: Cancer vaccines are a form of immunotherapy—treatment meant to boost a patient’s own immune system to fight cancer. Unfortunately, they have not proven very successful when tested in lung cancer patients in clinical trials. The disappointing trend continues with new results from a clinical trial testing a vaccine called MAGE-A3. However, we posted a story yesterday about scientists’ hopes that cancer vaccines may start working better when paired with certain drugs called checkpoint inhibitors.

“The MAGRIT trial showed disappointing results for a developmental vaccine called MAGE-3 in patients with non–small cell lung cancer (NSCLC) who had undergone surgical resection. This is the largest vaccine trial conducted in lung cancer, and investigators hoped that an immunotherapy approach with a vaccine would improve outcomes. The findings were presented at the ESMO 2014 Congress in Madrid (Abstract 1173O).

“At present, about 45% of patients are cured by surgery with or without chemotherapy, and better therapies are needed.

“ ‘Vaccinations give us effective soldiers, but in this case they didn’t work on the battlefield,’ stated lead author Johan F. Vansteenkiste, MD, Catholic University Leuven, Belgium. He noted that other trials have shown that lung cancer vaccines elicit antibodies and immune cells (ie, “soldiers”) that can kill cancer cells, ‘but the problem occurs when they come to the battlefield, ie, the environment of the tumor where they are paralyzed by factors in the tumor.’

“On the plus side, the MAGE-3 cancer vaccine was well tolerated and the investigational effort identified a predictive marker for treatment benefit—the MAGE-A3 protein. Of the nearly 13,500 NSCLC patients screened for the study, one-third had tumors that expressed MAGE-A3—similar to the expected distribution in NSCLC.”


Investigational MAGE-A3 Antigen-Specific Cancer Immunotherapeutic Does Not Meet First Co-Primary Endpoints in MAGRIT, a Phase III Non-Small Cell Lung Cancer Clinical Trial

“GlaxoSmithKline plc (LSE:GSK) today announced that analysis of the MAGRITi trial, a phase III trial of its MAGE-A3 cancer immunotherapeuticii in non-small cell lung cancer (NSCLC) patients, showed that the trial did not meet its first or second co-primary endpoint as it did not significantly extend disease-free survival (DFSiii) when compared to placebo in either the overall MAGE-A3 positive population (first co-primary endpoint) or in those MAGE-A3-positive patients who did not receive chemotherapy (second co-primary endpoint). GSK currently remains blinded to the overall trial data from the analysis of the first two co-primary endpoints to allow for the unbiased generation of a mathematical model to assess the third co-primary endpointiv.”

Editor’s note: This story is about a drug that is meant to boost the patient’s own immune system to fight lung cancer. The study has found no significant survival benefit of the drug, but the drug company hopes to find a sub-population of people with lung cancer for whom the drug will work. Learn more about immunotherapy and clinical trials.


Amgen Vaccine Triggers Immune Response in Advanced Melanoma -Study

“An experimental Amgen Inc cancer vaccine used to treat advanced melanoma, the deadliest form of skin cancer, proved effective in a late-stage study in shrinking tumors in a way that suggests the drug triggered the intended systemic immune response, according to data presented on Friday.

“The vaccine shrank tumors that were directly injected with the drug and tumors around the body that were not injected, according to the data.

“The drug, talimogene laherparepvec, also known as T-vec, is an engineered virus designed to replicate inside the injected tumor, killing cancer cells there, as well as prime the immune system to attack other cancer cells around body.”


Super Patient: Chelsea Price Takes Charge of Stage III Melanoma


Late in 2010, Chelsea Price’s boyfriend noticed that a mole on her upper back was scabbed and weeping. “It had always been there but he thought I should get it checked,” recalls Chelsea, who was then 23 years old. By the time her dermatology appointment rolled around, however, the mole had healed. “I almost cancelled,” she says.

Good thing she didn’t. At her follow-up appointment, her dermatologist casually said, “Hey, it’s melanoma.” Thinking he was kidding, Chelsea started laughing. When she realized he was serious, she was stunned. Continue reading…


At Last, Success Seen in Fighting Cancer with the Immune System

“Fundamental research — much of it done in Boston — has led to a shift in the scientific strategy for fighting some cancers, toward using drugs to activate a patient’s own immune system. An approach that was on the fringes of cancer therapy is suddenly the hottest trend in cancer drug development. On Monday, for example, Boston researchers presented data showing that nearly half of patients with advanced melanoma lived for two years after getting an experimental immune therapy called nivolumab, though multiple other therapies hadn’t worked for them. And drug companies have announced several deals recently to acquire companies developing immunotherapies. The frenzy of activity is an abrupt change for a field that had made big promises but failed to deliver for years.”


Squamous Lung Cancer ‘Master Protocol’ Brings Cancer Research into the 21st Century


Clinical trials help determine whether new cancer treatments are safe and effective, and they provide access to cutting-edge drugs that patients wouldn’t otherwise be able to have. But the clinical trial system is notoriously inefficient, slow, expensive, and laborious. Now, a new and ambitious clinical trial design called the Lung Cancer Master Protocol seeks to overhaul the system, promising to benefit patients and drug companies alike. Continue reading…


Infecting Just One Tumor with a Virus Could Boost the Systemic Effectiveness of Cancer Immunotherapy

“A Ludwig Cancer Research study suggests that the clinical efficacy of checkpoint blockade, a powerful new strategy to harness the immune response to treat cancers, might be dramatically improved if combined with oncolytic virotherapy, an investigational intervention that employs viruses to destroy tumors.

“Published today in the journal Science Translational Medicine, the study evaluated a combination therapy in which the Newcastle disease virus (NDV), a bird virus not ordinarily harmful to humans, is injected directly into one of two melanoma tumors implanted in mice, followed by an antibody that essentially releases the brakes on the immune response. The researchers report that the combination induced a potent and systemically effective anti-tumor immune response that destroyed the non-infected tumor as well. Even tumor types that have hitherto proved resistant to checkpoint blockade and other immunotherapeutic strategies were susceptible to this combined therapy.”

Editor’s Note: This story is about research that was performed in mice. For that reason, we cannot assume that similar results would happen for humans. However, viruses like the one explored here are already being used in people. To learn more about immunotherapy—cancer treatments that use the immune system to fight tumors—visit our Melanoma Basics.