Keytruda/Pembrolizumab Is on the Fast Track for Approval in the UK

“Pembrolizumab is a treatment for advanced skin cancer and is the first medicine to be approved through the Early Access to Medicines scheme (EAMS), launched in England last April.

“The idea is to get pioneering drugs to severely ill patients much sooner.

“Drugs signed off through EAMS have been scrutinised by regulators, weighing the risks and benefits.

“A green light by the Medicines and Healthcare products Regulatory Agency (MHRA) means doctors anywhere in the UK can prescribe the drug in question before normal licensing procedures – which can take years – are complete.”


First PD-1 Inhibitor in Lung Cancer May Soon Be Approved

The gist: This Q&A with an oncologist gives a good overview of a promising immunotherapy for non-small cell lung cancer (NSCLC). Immunotherapies are treatments that boost a patient’s own immune system to fight cancer. Based on good clinical trial results, the U.S. Food and Drug Administration (FDA) might soon approve a drug called nivolumab (Opdivo) for certain lung cancer patients. If it’s approved, doctors could prescribe it for patients with advanced, squamous NSCLC who have already tried two other treatments. Opdivo is a specific kind of immunotherapy called a PD-1 inhibitor.

“Immune checkpoint inhibitors targeted against PD-1 and its ligand PD-L1 have rapidly advanced as treatments for patients with melanoma and non–small cell lung cancer (NSCLC), following their initial debut in 2012.

“In the past 4 months alone, the PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) have each gained separate approvals as treatments for patients with advanced melanoma. Additionally, in mid-January, phase III findings from the CheckMate-017 study demonstrated that nivolumab extended overall survival compared with docetaxel in patients with pretreated squamous cell NSCLC.

“Based on these findings and those from phase II studies, Bristol-Myers Squibb (BMS) is currently in the process of submitting a New Drug Application to the FDA for nivolumab as a third-line treatment for patients with squamous cell NSCLC. Furthermore, several phase III studies are currently examining the agent across a variety of tumor types.”


Immune System-Boosting "Immune Checkpoint Inhibitors" Show Promise for Treating Many Kinds of Cancer

The gist: Drugs called “immune checkpoint inhibitors” have shown promise for patients with multiple types of cancer. Immune checkpoint inhibitors are a type of immunotherapy, meaning they boost a patient’s own immune system to fight cancer. Two particularly promising immune checkpoint inhibitor drugs are MPDL3280A and pembrolizumab.

“Treatment with an immune checkpoint inhibitor led to consistent responses across multiple types of cancer, particularly in patients with suppressed immune systems that appeared to be ‘reinvigorated’ by the therapy, investigators reported.

“Response rates of 20% to 25% were seen in patients with advanced cancers, including lung, kidney, and head and neck cancers, as well as melanoma. The overall response to the engineered antibody MPDL3280A increased to 46% in patients whose tumors exhibited overexpression of programmed death-ligand 1 (PD-L1), a protein associated with immune suppression in multiple types of cancer, as reported a research letter in Nature.

“The antitumor activity was encouraging, but the identification of markers predictive of response could prove to be equally important if not more so, according to Roy S. Herbst, MD, PhD, of the Yale Cancer Center.

” ‘The most compelling thing about the study is the fact that we worked to develop predictive markers for who responds and who doesn’t,’ Herbst told MedPage Today. ‘We can measure PD-L1 immunostaining in the immune infiltrate — not on the tumor cells but on the macrophages and the lymphocytes in the immune microenvironment.’ “


International Breast Cancer Study Group, Breast International Group and Merck Announce Opening of International PANACEA Study of Patients with HER2+ Breast Cancer

The gist: A new clinical trial will enroll patients to see whether combining the drug pembrolizumab (aka Keytruda) with trastuzumab (aka Herceptin) might help them overcome resistance to trastuzumab. Pembrolizumab is an immunotherapy, meaning it boosts a patient’s immune system to fight cancer. 

“The International Breast Cancer Study Group (IBCSG), Breast International Group (BIG), and Merck, known as MSD outside the United States and Canada, today announced the opening of the PANACEA study, a global collaborative study exploring a new way to treat HER2+ breast cancer that has become resistant to the current standard of care. The PANACEA study will investigate the use of pembrolizumab (KEYTRUDA®) in combination with trastuzumab to evaluate whether the addition of an anti-PD-1 therapy can reverse trastuzumab resistance in patients with HER2+ breast cancer whose cancer has spread while on trastuzumab therapy.

“Worldwide, breast cancer is the most common cancer among women.1 About one in five patients with breast cancer have too much of a growth-promoting protein known as HER2/neu (or just HER2) on the surface of cancer cells. Breast cancers with too much of this protein tend to grow and spread more aggressively.

“ ‘PANACEA is the first phase 2 immunotherapy trial not only in HER2+ breast cancer, but in the entire breast cancer field,’ said Sherene Loi, MD, PhD, study chair, division of cancer medicine, Peter MacCallum Cancer Centre, Australia. ‘If successful, this may herald a new treatment approach in certain types of breast cancer.’ ”


What's Intriguing And Concerning About Early Results For Keytruda In Breast Cancer

Note: This is an opinion piece about the recent news that the drug Keytruda has shown promise for treating triple-negative breast cancer (TNBC). It does not necessarily reflect the views of Cancer Commons.

“At first glance, it’s hard to get excited about the preliminary results of an early phase trial study of pembrolizumab (Keytruda, MK-3475) in women with triple-negative breast cancer (TNBC). The non-randomized study has, so far, yielded an overall response rate of 18.5 percent – only 5 among 27 evaluable patients.

“The findings drew attention at the San Antonio Breast Cancer Symposium, in part because TNBC is a notoriously hard-to-treat form of the disease. The work* was presented by Dr. Rita Nanda, of the University of Chicago, who led a multinational list of authors including academics and several Merck employees.

“Keytruda is a monoclonal antibody given by infusion. When it binds PD-1, as it’s engineered to do with high affinity, it can unleash the body’s normal immune cells to fight a tumor. Recently, the FDA approved Keytruda for use in advanced melanoma. Last week, at the annual meeting of the American Society of Hematology, investigators reported preliminary findings that the drug is well-tolerated and may be helpful in Hodgkin’s lymphoma.”


Amgen Initiates Study to Evaluate Combined Talimogene Laherparepvec, Keytruda for Melanoma

The gist: A new clinical trial will give patients a new treatment to treat their metastatic melanoma. (The trial is currently enrolling patients). The treatment combines talimogene laherparepvec (T-VEC) and Keytruda (pembrolizumab), both immunotherapies that boost a patient’s own immune system to fight cancer. The researchers running the clinical trial hope that the combination will work better than either treatment alone. Learn more about T-VEC in our latest blog post.

“Amgen announced the beginning of a study to evaluate the safety and efficacy of talimogene laherparepvec in combination with the investigational use of Merck’s pembrolizumab in patients with regionally or distantly metastatic melanoma, according to a press release.

“Talimogene laherparepvec is an investigational oncolytic immunotherapy and Keytruda (pembrolizumab) is a U.S. Food and Drug Administration-approved anti-PD-1 therapy. The trial has started enrollment and will evaluate the combined therapy in 110 patients at 35 clinical trial sites in the United States, Australia and Europe.

“ ‘Talimogene laherparepvec is designed to promote tumor antigen release and presentation to initiate an anti-tumor response, which may be complementary to Keytruda’s role in releasing PD-1 pathway-mediated inhibition of anti-tumor responses,’ F. Stephen Hodi, MD, steering committee chair for the study, said in the release.”


Early Trial of New Drug Shows Promise for Patients with Triple-Negative Breast Cancer

The gist: A drug called pembrolizumab (aka Keytruda or MK-3475) has shown promise for people with metastatic triple-negative breast cancer (TNBC) whose tumors have high levels of a protein called PD-L1.  It was recently tested in patients in a clinical trialPembrolizumab is already approved by the U.S. Food and Drug Administration (FDA) for treating melanoma. It is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. More research will determine just how well pembrolizumab might work for TNBC.

“In patients with metastatic triple-negative breast cancer—a disease with no approved targeted therapies—infusion of pembrolizumab produced durable responses in almost one out of five patients enrolled in a phase-Ib clinical trial, according to data presented Dec. 10, at the 2014 San Antonio Breast Cancer Symposium.

“The multi-center, non-randomized trial was designed to evaluate the safety, tolerability and antitumor activity of bi-weekly infusions of pembrolizumab (MK-3475, marketed as Keytruda®). The researchers enrolled 27 patients, aged 29 to 72 years, who had metastatic triple-negative breast cancer that either relapsed after treatment for early stage disease or progressed on therapy for advanced disease.

” ‘For this group of patients our treatment options are limited to chemotherapy,’ said study director Rita Nanda, MD, assistant professor of medicine and associate director of the breast medical oncology program at the University of Chicago.

“All patients in the study had triple-negative tumors with high levels of a protein called programmed death-ligand 1 (PD-L1). This protein can suppress the immune system’s efforts to eliminate cancer cells. Pembrolizumab is a monoclonal antibody designed to help reactivate a person’s own immune system to help fight the tumor.”


UCLA Scientists Discover Why Certain Patients Respond to a Life-Saving Melanoma Drug

“UCLA researchers have pioneered a new methodology to predict why some patients battling advanced melanoma respond well or not at all to the new breakthrough drug pembrolizumab (Keytruda).

“The study, led by UCLA Jonsson Comprehensive Cancer Center members Drs. Paul Tumeh and Antoni Ribas, primary investigator of pembrolizumab, is the first of its kind since the FDA approved the use of Keytruda in September and could lead the way for more effective use of the drug in patients with melanoma and other cancers.

“A protein known as PD-1 puts the immune system’s brakes on, preventing T cells from attacking cancer cells. Pembrolizumab removes the brake lines, freeing up the immune system to kill cancer cells.”


UC San Francisco and OncoSec Medical Collaborate to Evaluate Investigational Combination of ImmunoPulse and Anti-PD-1 Treatment

The gist: Two drug companies are teaming up to see wether two melanoma treatments can work better together than either on its own. The treatments are Keytruda (aka pembrolizumab) and ImmunoPulse. Both drugs use a patient’s own immune system to fight cancer.

“OncoSec Medical Inc. (OTCQB: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, has entered a clinical collaboration with the University of California, San Francisco (UCSF), to evaluate the safety, tolerability and efficacy of the combination of KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, and OncoSec’s ImmunoPulse (intratumoral IL-12) in metastatic melanoma.

“Recent data suggest that patients who are PD-L1 positive and have increased tumor-infiltrating lymphocytes (TILs) are more likely to respond to anti-PD-1/PD-L1 mAbs compared to patients who are PD-L1 negative. Therefore, therapies that promote TIL generation and PD-L1 positivity may play an important role in augmenting the clinical efficacy of these agents.

“Interleukin-12 (IL-12) is an inflammatory cytokine believed to be a master regulator of the immune system, promoting up-regulation of both the innate and adaptive immune responses. More specifically, IL-12 stimulates the production of another cytokine, interferon gamma (IFN-), which results in the stimulation of antigen processing and presentation machinery, leading to increased TILs and anti-tumor cytotoxic T-cell (CTL) activity.”