UPDATE 2-Bristol's Opdivo Proves Effective Against Second Type of Lung Cancer

“A large study of Bristol-Myers Squibb Co’s Opdivo treatment has been halted after proving the drug is effective against the most common form of lung cancer, the company said, positioning the medicine for far wider use than its already approved lung cancer and melanoma indications.

“The U.S. drugmaker on Friday said the study, called Checkmate-057, was stopped early after an independent data monitoring committee concluded that Opdivo provided a survival advantage over docetaxel, a standard chemotherapy, among patients with previously treated non-squamous non-small cell lung cancer (NSCLC).

“The so-called PD-1 inhibitor, which works by taking the brakes off the immune system, was approved by U.S. regulators last month to treat the less-common “squamous” form of NSCLC that had spread following treatment with chemotherapy.

“Opdivo is also approved for use against metastatic melanoma following treatment with Yervoy, another Bristol-Myers immuno-therapy.”


Nivolumab Beats Chemotherapy in Melanoma That Has Not Responded to Ipilimumab

“In the phase III CheckMate 037 trial reported in The Lancet Oncology, Weber et al found that treatment with the PD-1 inhibitor nivolumab (Opdivo) resulted in a significantly greater response rate vs chemotherapy as second- or later-line treatment in patients with advanced melanoma progressing after anti–CTLA-4 treatment. Findings in this trial supported the accelerated approval of nivolumab in this setting in December 2014.

“In this open-label trial, 405 patients with unresectable or metastatic melanoma from 90 sites in 14 countries were randomly assigned 2:1 between December 2010 and January 2014 to receive nivolumab (n = 272) or chemotherapy (n = 133). Patients had to have progressed after treatment with ipilimumab (Yervoy) or with ipilimumab and a BRAF inhibitor if they were BRAF V600 mutation–positive. Nivolumab was given at 3 mg/kg intravenously every 2 weeks. Dose delay but not reduction was permitted in nivolumab patients. Investigator’s choice of chemotherapy consisted of dacarbazine 1,000 mg/m2 every 3 weeks or paclitaxel 175 mg/m2 combined with carboplatin area under the curve = 6 every 3 weeks. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoints of the trial are objective response and overall survival. In the current report of the first interim analysis, objective response was assessed after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks…

“The investigators concluded: ‘Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor. Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need.’ ”


Is There a Future for Immunotherapy in Breast Cancer?


Lately, immunotherapy—treatment that helps the body’s own immune system fight cancer—has made frequent appearances in news headlines. Indeed, researchers have reported remarkable clinical trial results for a new class of drugs known as ‘immune checkpoint blockade drugs‘ in the treatment of metastatic melanoma, lung, and kidney cancers. Approvals from the U.S. Food and Drug Administration (FDA) for the drugs Keytruda and Opdivo for melanoma and lung cancer have quickly followed. However, it may be that immunotherapies won’t work for all cancers, but only for those considered to be ‘immunogenic’; that is, cancers that trigger activation of the immune system. Researchers are studying different types of breast cancer to determine whether they are immunogenic, and what that might mean for their prognosis and treatments. Continue reading…


Nivolumab Works in Melanoma Patients for Whom Previous Treatments Did Not

“More patients with advanced melanoma who had progressed on ipilimumab with or without a BRAF inhibitor were able to achieve an objective response when treated with the PD-1 immune checkpoint inhibitor nivolumab than with alternative chemotherapy options, according to the interim analysis results of the CheckMate 037 trial published recently in Lancet Oncology.

“In fact, the rate of objective response was about threefold greater with nivolumab compared with investigator’s choice of chemotherapy; however, no difference in progression-free survival in the intention-to-treat population was noted.

“These results were the basis of the December 2014 US Food and Drug Administration accelerated approval of nivolumab for this patient population.

“ ‘Findings from our study show that nivolumab leads to clinically meaningful improvements in the proportion of patients achieving an objective response and provide a manageable safety profile when compared with chemotherapy,’ wrote Jeffrey S. Weber, MD, of Moffitt Cancer Center, Tampa, Florida, and colleagues. ‘Nivolumab can now be considered as a new treatment option for patients that have progressed after ipilimumab, or a BRAF inhibitor and ipilimumab if their melanoma is BRAF V600–mutated.’ ”


Opdivo Approved for Squamous Lung Cancer

“Bristol-Myers Squibb (BMY) secured an expanded U.S. approval Wednesday for the use of its checkpoint inhibitor Opdivo to treat a form of advanced lung cancer.

“The new Opdivo approval covers patients with squamous non-small cell lung cancer no longer responsive to chemotherapy, according to an announcement made by the FDA. In December, Bristol’s drug was approved initially to treat skin cancer.

“The FDA moved exceptionally fast expanding Opdivo’s approval. Bristol said the lung cancer application was accepted last week with an approval decision expected in June.

“The worldwide commercial market for squamous cell lung cancer patients tops $3 billion, according to an analysis by Barclays.”


U.S. Food and Drug Administration Accepts Biologics Licensing Application for Opdivo (Nivolumab) for the Treatment of Advanced Squamous Non-Small Cell Lung Cancer

“Bristol-Myers Squibb Company today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and review the Biologics Licensing Application (BLA) for Opdivo (nivolumab)for the treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) after prior therapy. The FDA also granted Priority Review for this application. The Prescription Drug User Fee Act (PDUFA) goal date for a decision is June 22, 2015.

“In the U.S., lung cancer is one of the leading causes of cancer deaths. Non-small cell lung cancer, one of the most common types accounting for approximately 85 percent of cases, includes three main subtypes including squamous NSCLC. Squamous NSCLC accounts for approximately 25 to 30 percent of all lung cancers.

“ ‘With the acceptance of our application for Opdivo in the squamous non-small cell lung cancer setting, Bristol-Myers Squibb marks another significant milestone in its goal to deliver a new treatment option for this challenging to treat patient population,’ said Michael Giordano, MD, senior vice president, Head of Oncology Development, Bristol-Myers Squibb. ‘As a company that prides itself in helping patients prevail over deadly diseases, we are proud of this achievement and look forward to making Opdivo available to the lung cancer community.’ ”


Companies Work Together to Address Need for a Test to Identify Lung Cancer Patients Who Might Benefit from Opdivo

“Agilent subsidiary Dako and Ono Pharmaceutical are working together to investigate and advance a diagnostic test that will identify which non-small cell lung cancer patients are likely to respond to Opdivo (nivolumab).

” ‘This test is being investigated for its diagnostic utility,’ the companies said, in order to identify best responders to Opdivo. The drug works by inhibiting PD-1, a protein that impedes the body’s ability to launch an immune attack against cancer cells.

“The US Food and Drug Administration in December granted accelerated approval of Opdivo as a treatment for advanced or unresectable melanoma patients who are no longer responding to other drugs. Additionally, Ono also received regulatory approval in Japan for Opdivo for the same indication in July.

“In the US, Bristol-Myers Squibb sells Opdivo. BMS holds global development and commercialization rights to Opdivo, except in Japan, South Korea, and Taiwan, where Ono retains all rights for the compound.”


Immune System-Boosting Drug Combo to Begin Testing in Patients in New Clinical Trial

The gist: A new drug combination will be tested in patients with advanced non-small cell lung cancer (NSCLC), metastatic melanoma (MEL), colorectal cancer (CRC), ovarian cancer, or head and neck squamous cell carcinoma (SCCHN). The treatment combines the drugs varlilumab and nivolumab (Opdivo). Both drugs are immunotherapies; they activate a patient’s own immune system to fight cancer. The trial will test the safety of the combo and see how well it works.

“Celldex Therapeutics, Inc. (NASDAQ: CLDX) and Bristol Myers-Squibb (NYSE: BMY) today announced the initiation of a Phase 1/2 dose escalation and cohort expansion study examining the investigational combination of varlilumab, Celldex’s CD27 targeting investigational immune-activating antibody and Bristol-Myers Squibb’s immunotherapy Opdivo (nivolumab). The study will be conducted in adult patients with advanced non-small cell lung cancer (NSCLC), metastatic melanoma (MEL), colorectal cancer (CRC), ovarian cancer, and head and neck squamous cell carcinoma (SCCHN). Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells. This study will evaluate the safety and tolerability of the combination and address the hypothesis that the combination of these two mechanisms enhance the anti-tumor activity compared to either agent alone. Celldex is responsible for conducting the study and development costs will be shared.”


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.”