New Long-Term Data on Opdivo and the Opdivo + Yervoy Regimen Shows Survival Benefit Across Lines of Therapy in Advanced Melanoma

“Bristol-Myers Squibb Company (NYSE:BMY) today announced new long-term data of Opdivo in treatment-naïve BRAF wild-type advanced melanoma from CheckMate -066. In the trial, Opdivo continued to demonstrate superior overall survival versus dacarbazine with 57.7% of patients alive at two years compared to 26.7% of patients treated with dacarbazine. The safety profile of Opdivo was consistent with prior studies. The two-year survival and safety data from CheckMate -066 represent the longest follow-up from a randomized study of any PD-1 immune checkpoint inhibitor in the first-line setting of advanced melanoma. These data will be presented as a late-breaking presentation at the Society for Melanoma Research (SMR) 2015 International Congress in San Francisco, CA from November 18 to 21.”


Ipilimumab plus Radiotherapy May Benefit Patients with Metastatic Melanoma

“The combination of ipilimumab and palliative radiation therapy reduced tumor growth and the spread of metastases in some patients with metastatic melanoma, according to prospective, phase 2 study results presented at the ASTRO Annual Meeting.

“Local radiation therapy has the potential to augment the induction of systemic anti-melanoma immune responses when used in combination with systemic anti–CTLA-4 immunotherapy, according to study background.

“Thus, Susan M. Hiniker, MD, instructor in the department of radiation oncology at Stanford University School of Medicine, and colleagues assessed the safety and efficacy of combining ipilimumab (Yervoy, Bristol-Myers Squibb) with palliative radiotherapy in patients with stage IV melanoma. Researchers also assessed the induction of anti-melanoma immune response.

“The analysis included data from 20 patients (men, n = 14) aged 18 to 83 years who had stage IV melanoma. Patients received palliative radiotherapy and 3 mg/kg IV ipilimumab every 3 weeks for four treatment cycles. The radiotherapy was initiated within 5 days of the first ipilimumab treatment at one or two melanoma sites.”


Bristol-Myers Squibb Receives Approval from the U.S. Food and Drug Administration for Yervoy (ipilimumab) as Adjuvant Treatment for Fully Resected Stage III Melanoma

Bristol-Myers Squibb Company BMY, -0.27% today announced that the U.S. Food and Drug Administration (FDA) has approved Yervoy (ipilimumab) 10 mg/kg for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection including total lymphadenectomy. This approval is based on clinical data from a pivotal Phase 3 trial, CA184-029 (EORTC 18071), which demonstrated Yervoy 10 mg/kg significantly improved recurrence-free survival (RFS) vs. placebo in this setting, with a 25 percent reduction in the risk of recurrence or death. The median RFS was 26 months (95% ci:19)(95% ci:39) for Yervoy vs. 17 months (95% ci:13)(95% ci:22) for placebo (hazard ratio [HR]=0.75; 95% CI: 0.64, 0.90; p<0.002). Yervoy is the first and only FDA-approved immune checkpoint inhibitor in the adjuvant treatment for fully resected Stage III melanoma (lymph node >1 mm).”


A Subset of Patients with Metastatic Melanoma Achieves Clinical Benefit from Combination of Immunotherapy and Radiation Therapy

“Immunotherapy combined with palliative radiation therapy (RT) for a subset of patients with metastatic melanoma reduces the growth and spread of the cancer, according to research presented today at the American Society for Radiation Oncology’s (ASTRO’s) 57th Annual Meeting.

“Although melanoma is not the most common type of skin cancer, it is the most serious type. Stage IV melanoma indicates that the cancer has metastasized and spread through lymph nodes to distant sites in the body and/or to the body’s organs. The liver, lungs, bones and brain are areas most frequently affected by these metastatic lesions. Immunotherapy—the use of medicines to stimulate a patient’s own immune system to recognize and destroy cancer cells more effectively—can be combined with other cancer therapies to aid in the treatment of stage IV melanoma. Ipilimumab is an immunotherapy approved for use in melanoma patients.

“This phase II clinical trial is one of the first prospective clinical trials to report results from the treatment of metastatic melanoma with the combination of RT and systemic immunotherapy. In this study, 20 patients with stage IV melanoma were treated with palliative RT and intravenous ipilimumab (3mg/kg) every three weeks, for a total of four treatment cycles. RT was initiated to one or two sites of metastatic melanoma within five days of the initial immunotherapy treatment. All patients had at least one nonirradiated (untreated) site of metastasis that could be used for assessment of response to therapy.”


Video: Dr. Kunz on Potential of Immunotherapy in Neuroendocrine Tumors

“Pamela L. Kunz, MD, assistant professor of Medicine (Oncology), Stanford University School of Medicine, discusses the potential of immunotherapy in the treatment of patients with neuroendocrine tumors (NETs).

“There are currently some clinical trials under development looking at immunotherapy in NETs both at Stanford University School of Medicine and University of Pennsylvania, Kunz explains. One phase I/II trial will examine the safety and efficacy of intratumoral injection of ipilimumab combined with an anti—PD-L1 agent in these patients.”

“It is possible that immunotherapy agents could be agnostic to disease sites, Kunz says. Though it was originally believed that PD-1/PD-L1 expression is a requirement to be a predictive biomarker, additional research could show that it may not be necessary.”

Click through to watch the video.


Nivolumab/Ipilimumab Combination FDA Approved for BRAF Wild-Type Melanoma

“The combination of nivolumab and ipilimumab has received accelerated FDA approval as a treatment for patients with BRAF V600 wild-type (WT) unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study.

” ‘Historically, metastatic melanoma has been a difficult disease to treat. Now, a new treatment option based on the combination of two valued immuno-oncology agents demonstrates significant efficacy versus ipilimumab in metastatic melanoma,’ said Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, in a statement. ‘Today’s approval represents a step forward for the melanoma community, providing hope for patients with metastatic melanoma.’ ”


FDA Grants Priority Review of Opdivo plus Yervoy in Previously Untreated Advanced Melanoma

“The FDA has accepted a supplemental biologics license application for the Opdivo plus Yervoy regimen to include data from a phase 3 trial of patients with previously untreated advanced melanoma, according to a press release from Bristol-Myers Squibb.

“The agency also granted priority review of the application, with a target action date of Jan. 23, according to the release

” ‘Findings from CheckMate -067 provide additional evidence that the combination of the two immuno-oncology agents, Opdivo [nivolumab] and Yervoy [ipilimumab], may provide improved outcomes for patients with advanced melanoma, and has the potential to become the basis of how this devastating disease is treated,’ Michael Giordano, senior vice president, head of development for oncology at Bristol-Myers Squibb, said in a press release. ‘We saw significant clinical benefit from the Opdivo+Yervoy regimen in these patients, including an increase in the time patients lived without disease progression, and we look forward to working with the FDA to review this data.’ “


Drug Combination Improves Progression-Free Survival in Melanoma Patients

“Patients with advanced melanoma skin cancer survive for longer without their disease progressing if they have been treated with a combination of two drugs, nivolumab and ipilimumab, than with either of these drugs alone. New results show that these patients also do better regardless of their age, stage of disease and whether or not they have a cancer-driving mutation in the BRAF gene.

“Dr James Larkin, a Consultant Medical Oncologist at The Royal Marsden, London, UK, told the 2015 European Cancer Congress, that results from the CheckMate 067 phase III clinical trial had already shown that the combination of the two drugs, which target two different pathways that regulate the immune system, improved the progression-free survival in patients with melanoma who had not received any other treatment. However, until now it was not known whether this remained the case when the results were analysed according to genetic status, age and how advanced was their disease.

“Nivolumab is an inhibitor of the protein 1 (known as PD-1), which functions as an immune checkpoint, playing an important role in the immune system. Ipilimumab inhibits the CTLA-4 checkpoint, which also plays a role in the immune system.”


Nivolumab and Ipilimumab Combination Active as First-Line Therapy for Advanced NSCLC

“Nivolumab (Opdivo) and ipilimumab (Yervoy), a chemotherapy-free regimen, showed activity as a first-line therapy for patients who have advanced non-small cell lung cancer (NSCLC), according to a preliminary clinical trial that was presented at this year’s World Conference on Lung Cancer.

“Four different regimens of nivolumab, the PD-1 inhibitor, and ipilimumab, the anti-CTLA-4 antibody, led to response rates of 13% to 39% in 148 patients with no prior exposure to systemic therapy. The combination produced deep and durable responses, with a low rate of treatment-emergent grade 3/4 adverse events (AEs) leading to discontinuation.

“ ‘Clinical activity was observed regardless of tumor PD-L1 expression,’ said lead investigator Naiyer A. Rizvi, MD, director of Thoracic Oncology and Immunotherapeutics at Columbia University Medical Center. ‘We have preliminary evidence of greater activity in tumors that have 1% or greater PD-L1 expression. The median disease control rate [response plus stable disease] was not reached in any arm, regardless of PD-L1 expression.’ “