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.”
The gist: The drug KEYTRUDA (pembrolizumab) might be better than chemotherapy for people with melanoma that is metastatic or can’t be surgically removed, and who tried treatment with the drug ipilimumab without success. That was the conclusion of a recent clinical trial with volunteer patients. KEYTRUDA is an immunotherapy drug, meaning that it boosts the immune system to fight cancer.
“Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today that a pre-specified analysis of investigational data from a pivotal Phase 2 study (KEYNOTE-002) showed KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, substantially improved the primary endpoint of progression-free survival (PFS, as assessed by RECIST 1.1, independent central review) (HR 0.57 and 0.50 for 2 mg/kg and 10 mg/kg every three week doses, respectively), compared to chemotherapy (P<0.0001 for both comparisons) in patients with ipilimumab-refractory advanced melanoma (n=540). At six months, the PFS rates for KEYTRUDA were 34 percent at the 2 mg/kg dose (95% CI, 27-41) (n=180) and 38 percent at the 10 mg/kg dose (95% CI, 31-45) (n=181), compared to 16 percent for chemotherapy (95% CI, 10-22) (n=179). The median duration of follow-up at the interim analysis was 10 months.
“These findings, including pre-specified analyses of overall response rate (ORR), duration of response, safety and health-related quality of life (HRQoL), were presented today in an oral session by Dr. Antoni Ribas, professor, Hematology/Oncology and Surgery, and director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles at the Society of Melanoma Research (SMR) 2014 International Congress in Zurich, Switzerland.”
The gist: The U.S. Food and Drug Administration (FDA) has granted “breakthrough therapy designation” to the drug Keytruda (aka pembrolizumab) for treating certain lung cancer patients. This designation means that review and approval will be accelerated so that the drug can more quickly reach patients in the U.S., outside of clinical trials.Keytruda is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer. The breakthrough therapy designation specifically applies to patients with advanced non-small cell lung cancer (NSCLC) whose tumors have tested negative for EGFR mutation and ALK rearrangement, and whose disease worsened despite treatment with platinum-based chemotherapy.
“Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy. This is the second Breakthrough Therapy Designation granted for KEYTRUDA.
“ ‘The FDA’s Breakthrough Therapy Designation of KEYTRUDA underscores that new treatment approaches for advanced non-small cell lung cancer continue to be needed,’ said Dr. Roger Perlmutter, president, Merck Research Laboratories. ‘Our data investigating the use of KEYTRUDA in this difficult-to-treat malignancy are very encouraging, and we look forward to working closely with the FDA to expedite our clinical program.’ ”
The gist: A drug called pembrolizumab (brand name Keytruda) is effective for treating people with melanoma that does not respond to treatment with the drug ipilimumab (Yervoy). That is the conclusion of a recent clinical trial—a research study with volunteer patients. Based on the study, the U.S. Food and Drug Administration (FDA) has already approved Keytruda for treating melanoma that is advanced or unresectable (can’t be removed by a surgeon) and is not responding well to other drugs.
“As reported in The Lancet by Robert et al, the anti–programmed-death receptor-1 (PD-1) antibody pembrolizumab (Keytruda) produced durable responses in a phase I trial in patients with ipilimumab (Yervoy)-refractory melanoma. The study provided the basis for the recent accelerated approval of pembrolizumab for treatment of patients with unresectable or metastatic melanoma with disease progression following treatment with ipilimumab and, in BRAF V600 mutation–positive patients, treatment with a BRAF inhibitor. Pembrolizumab is the first PD-1 inhibitor to be approved for use in the United States…
“In this open-label, international, multicenter expansion cohort of a phase I trial, 173 patients aged ≥ 18 years with advanced melanoma progressing after at least two ipilimumab doses were randomly assigned to receive pembrolizumab intravenously at 2 mg/kg (n = 89) or 10 mg/kg (n = 84) every 3 weeks until disease progression, intolerable toxicity, or consent withdrawal. The primary endpoint was overall response rate. Overall, 97% of patients were white, 17% had BRAF V600 mutant disease, and 73% had received at least two prior therapies for advanced or metastatic disease.”
The gist: A new drug called pembrolizumab has shown promise for treating several cancer types, including melanoma and non-small cell lung cancer (NSCLC). Pembrolizumab is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. It has been tested in several clinical trials—research studies with volunteer patients. In one trial, pembrolizumab showed benefits for advanced NSCLC patients. It might be particularly effective for patients whose tumors have high expression of the protein PD-L1. There are ongoing pembrolizumab clinical trials that NSCLC patients can enroll in. Another clinical trial compared different pembrolizumab dosing schedules for melanoma patients. In fact, pembrolizumab, also known as Keytruda, has already been approved by the U.S. Food and Drug Administration (FDA) for certain kinds of melanoma patients.
“Results from the studies of pembrolizumab in advanced non-small-cell lung cancer (NSCLC), melanoma, gastric cancer, urothelial cancer and head and neck carcinoma, presented during the ESMO 2014 Congress (Madrid, Spain), show promising activity and tolerability from this novel monoclonal antibody.
“PD-1 is a negative co-stimulatory receptor expressed primarily on activated T cells. Binding of PD-1 to its ligands inhibits effector T-cell function. Expression of PD-L1 on tumour cells and macrophages can suppress immune surveillance and permit neoplastic growth.
“Pembrolizumab is able to achieve a dual blockade (PD-L1 and PD-L2). It shows no cytotoxic (ADCC/CDC) activity. Pharmacokinetics support dosing every 2 weeks (Q2W) or every 3 weeks (Q3W). Pembrolizumab demonstrated a clinical activity in multiple tumour types…
“The anti-PD-1 antibody pembrolizumab has shown durable antitumour activity and acceptable toxicity in treatment-naïve and previously treated advanced NSCLC patients. Correlation between tumour PD-L1 expression and improved pembrolizumab antitumour activity has been observed. Prof. Edward Garon of the David Geffen School of Medicine at UCLA, Santa Monica, USA presented analysis in 282 patients with treatment-naïve or previously treated advanced NSCLC enrolled in randomised and non-randomised cohorts of the phase I KEYNOTE-001. The results were presented during the Proffered Paper session in metastatic NSCLC.”
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.”
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.”
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.”
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.”