Combination of Standard-Dose Pembrolizumab With Reduced-Dose Ipilimumab Tolerable and Effective in Advanced Melanoma


“The combination of the programmed death receptor 1 (PD-1) inhibitor nivolumab at a reduced dose (1 mg/kg) with the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor ipilimumab at standard dose (3 mg/kg) for four doses followed by standard-dose nivolumab alone is a standard of care for patients with advanced, previously untreated melanoma. This is based on results from the phase III CheckMate-067 trial that confirmed combination therapy is significantly more effective than single-agent nivolumab or ipilimumab. However, improvement in efficacy is associated with increased treatment-related grade 3/4 adverse events and treatment discontinuation in nearly 40% of patients.”

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ASCO: Targeting PD-1 Works in Advanced Melanoma

“Two studies indicate that using investigative immunotherapy drugs improves survival and response in patients with metastatic melanoma, researchers said here.

“In one study, the agent pembrolizumab (MK-3475) which targets the programmed death (PD-1) pathway produced a 1-year 69% survival rate, said Antoni Ribas, MD, PhD, professor of medicine at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles.

“In a second study reported in a press conference at the annual meeting of the American Society of Clinical Oncology, Mario Sznol, MD, professor of medicine at the Yale Cancer Center, demonstrated that a combination of the investigative PD-1 inhibitor nivolumab in combination with another targeted agent ipilimumab (Yervoy) produced a 1-year survival rate of 85% and 2-year survival rate of 79% for advanced melanoma patients.”

Editor’s note: Immunotherapy drugs boost a patient’s own immune system to fight cancer. Promising research into new immunotherapy drugs for melanoma was recently presented at the American Society of Clinical Oncology (ASCO) Annual Meeting. Two treatments that received special attention were MK-3475 (aka pembrolizumab) and a combination of the drugs ipilimumab (Yervoy) and nivolumab.

Ipilimumab Nivolumab Combination Demonstrated Encouraging Activity in Advanced Melanoma

“The combination of the immunotherapy agents ipilimumab and nivolumab induced extensive and durable tumor shrinkage in patients with advanced melanoma, according to long-term study results presented at the ASCO Annual Meeting.

“ ‘These are two distinct immune checkpoint inhibitors, so it makes sense to combine them together,’ researcher Mario Sznol, MD, a professor of medical oncology at Yale School of Medicine, said during a press conference. ‘They both produce very significant clinical activity as monotherapy in advanced melanoma.’ ”

Editor’s note: Immunotherapy treatments boost a patient’s own immune system to fight cancer. A new immunotherapy treatment combines two individual immunotherapy drugs: ipilimumab (Yervoy) and nivolumab. In a clinical trial to test the combo in volunteer patients with advanced melanoma, the treatment was found to provide promising survival results. Further studies are needed to see just how well the treatment might work.

Two Array-Invented MEK Inhibitors Showcased At ASCO

“Two Array BioPharma-invented MEK inhibitors, binimetinib (MEK162) and selumetinib, were showcased at the 50th annual meeting of the American Society of Clinical Oncology (ASCO).  At the meeting, preliminary data for the combination of binimetinib and CDK4/6 inhibitor LEE011 (discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals) from a Phase 1b/2 dose-escalation study conducted by Novartis in NRAS-mutant melanoma indicates the combination demonstrated an acceptable safety profile for most patients with promising preliminary antitumor activity.  Additionally, preliminary data for selumetinib showed favorable clinical activity in pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs).”

Editor’s note: This article discusses a melanoma treatment that combines two durgs: binimetinib (aka MEK162) and selumetinib. A clinical trial recently found that the combo shows promise for melanoma patients whose tumors have mutations in the NRAS gene, as detected by molecular testing. Binimetinib is also being tested as a potential treatment for patients whose tumors have mutations in the BRAF gene.

Incyte : Announces Preliminary Results of a Phase I/II Study of Combination Immunotherapy in Patients with Melanoma

“Incyte Corporation (Nasdaq: INCY) today announced that preliminary results from an ongoing Phase I/II study of INCB24360, its oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with ipilimumab in patients with unresectable or metastatic melanoma were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30 to June 3, 2014, in Chicago. The poster reported initial findings showing that the combination was generally well tolerated and produced evidence of clinical response.”

Editor’s note: This article discusses a new treatment for melanoma that combines a drug called INCB24360 with the drug ipilimumab (Yervoy). Both drugs are immunotherapies, meaning they boost a patient’s own immune system to fight cancer. A clinical trial testing the combo in volunteer patients found promising preliminary results.

Long-Term Results Encouraging for Combination Immunotherapy for Advanced Melanoma

“The first long-term follow-up results from a phase 1b immunotherapy trial combining drugs for advanced melanoma patients has shown encouraging results—long-lasting with high survival rates—researchers report. First author Mario Sznol, M.D., professor of medical oncology at Yale Cancer Center, is presenting the updated data at the 2014 annual conference of the American Society of Clinical Oncology (ASCO) in Chicago.

“Sznol, clinical research leader of the melanoma research program at Yale Cancer Center, was the senior author on the original study of combination immunotherapy that was first published in the New England Journal of Medicine and presented at ASCO in 2013. Jedd Wolchok, M.D., of Memorial Sloan Kettering Cancer Center was first author of the earlier study, and senior author of this updated research.”

Editor’s note: Immunotherapy treatments boost a patient’s own immune system to fight cancer. This story describes a promising treatment that combines two immunotherapy drugs: nivolumab and ipilimumab (Yervoy).

Combination Dabrafenib/Trametinib Increased PFS in BRAF-Positive Melanoma

“Data from a phase 3 trial demonstrate combination dabrafenib and trametinib was superior to dabrafenib plus placebo for improved PFS in patients with BRAFV600-positive metastatic melanoma, according to data presented here at the ASCO Annual Meeting.

“ ‘This is the first melanoma trial, phase 3, to have an active control arm,’ researcher Georgina V. Long, BSc, PhD, MBBS, FRCP, oncologist at Melanoma Institute Australia at the University of Sydney, said of the COMBI-D trial.”

Editor’s note: This story describes the results of a clinical trial, in which volunteer patients are help test a new treatment. The treatment consists of a combination of the targeted therapy drugs dabrafenib and trametinib. Patients treated with the combination lived longer without progression of their cancer than patients who received dabrafenib plus a non-active placebo. Importantly, these results are specific to patients whose tumors have “BRAF V600E” mutations, which doctors can detect via molecular testing.

Conference Abstract – MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients With Acquired Resistance to Combined RAF/MEK Inhibition

“Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP–ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. This study represents an initial clinical genomic study of acquired resistance to combined RAF/MEK inhibition in BRAF-mutant melanoma, using WES and RNA-seq. The presence of diverse resistance mechanisms suggests that serial biopsies and genomic/molecular profiling at the time of resistance may ultimately improve the care of patients with resistant BRAF-mutant melanoma by specifying tailored targeted combinations to overcome specific resistance mechanisms.”

Editor’s note: We previously covered the benefits of a dabrafenib/trametinib combo for advanced-stage melanoma. However, some patients’ tumors become resistant to this drug combination and new treatment routes need to be considered. This study is exploring how molecular testing of specific genetic mutations in patients’ tumors might be used to help guide treatment decisions after they become resistant to the dabrafenib/trametinib combo.

New Treatments for Advanced Melanoma Presented at AAD

“In recent years, the FDA has approved new drugs for the treatment of advanced melanoma, which has presented new ways to treat the disease, according to a presentation at the American Academy of Dermatology annual meeting.

“ ‘In the last four years there have been four new drugs that have been FDA-approved for melanoma and what’s even more exciting is that they really speak to two new ways to treating melanoma,’ Allan C. Halpern, MD, MSc, chief of dermatology service at Memorial Sloan-Kettering Cancer Center, told

“The most recent FDA approval, in January, was the combination of a BRAF inhibitor and a MEK inhibitor for treating advanced melanoma.”