“Incyte Corporation (Nasdaq:INCY) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the decision to advance the clinical development program investigating the combination of epacadostat, Incyte’s investigational oral selective IDO1 inhibitor, with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy.
“With the expansion of the clinical development program, the companies plan to initiate pivotal studies of epacadostat in combination with KEYTRUDA in four additional tumors: non-small cell lung cancer, renal cell carcinoma, bladder cancer and squamous cell carcinoma of the head and neck. Presentations of data from the ongoing studies of epacadostat in combination with KEYTRUDA, which support this decision, are expected at upcoming medical meetings.”
“Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai Inc. today announced new interim data investigating Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in combination with Eisai’s microtubule dynamics inhibitor, HALAVEN® (eribulin) in patients with metastatic triple-negative breast cancer (TNBC). Findings presented during the 2016 San Antonio Breast Cancer Symposium (SABCS) were based on interim data from 39 evaluable patients and showed an overall response rate (ORR) of 33.3% (n=13/39; 95% CI, 19.5-48.1), with one complete response and 12 partial responses (Abstract #: P5-15-02). ORR was similar between PD-L1-positive and -negative cohorts [PD-L1 positive=29.4% (n=5/17; 95% CI, 11.1-51.1); PD-L1 negative=33.3% (n=6/18; 95% CI, 14.1-54.6)]. HALAVEN and KEYTRUDA are not approved for use in combination.”
“Neoadjuvant immunotherapy with the programmed cell death protein 1 (PD-1) inhibitor nivolumab (Opdivo) is safe and feasible in early-stage non–small cell lung cancer (NSCLC). The results come from the first report of PD-1 blockade prior to surgery in this tumor, according to Patrick Forde, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, who reported these findings at the 2016 European Society for Medical Oncology (ESMO) Congress.
” ‘Thirty-nine percent of patients with early-stage NSCLC treated with two doses of nivolumab had major pathologic responses associated with immune cell infiltration of tumor,’ Dr. Forde reported. ‘One hypothesis is that having tumor in situ when you give anti–PD-1—having more antigen present—may be better than giving it in the adjuvant setting, where only micrometastases may be present.’ ”
Last year, the U.S. Food and Drug Administration (FDA) approved two anti-PD-1 checkpoint inhibitors, a type of immunotherapy, for treatment of non-small cell lung cancer (NSCLC) in patients whose cancer has progressed after first-line treatment with chemotherapy. Now, the manufacturers of both drugs, pembrolizumab (made by Merck) and nivolumab (made by Bristol-Myers Squibb; BMS) are intent on expanding the indications for use of their drugs. To this end, they have conducted clinical trials testing each as a first-line treatment (i.e., in previously untreated patients), comparing them to standard chemotherapy. Continue reading…
“The addition of PD-1 antibody pembrolizumab to standard first-line chemotherapy for treatment-naïve advanced non-small-cell lung cancer significantly improves response rates and progression-free survival, researchers reported at the ESMO 2016 Congress in Copenhagen today.
“Pembrolizumab is a class of immunotherapeutic anti-cancer drugs called checkpoint inhibitors, which target the mechanism the tumour uses to shut down the body’s immune response.”
“Neoadjuvant immunotherapy with the PD-1 inhibitor nivolumab is safe and feasible prior to surgery for early lung cancer, researchers reported at the ESMO 2016 Congress in Copenhagen.
” ‘Until now nivolumab and the other anti-PD-1 and anti-PD-L1 drug studies have only been reported in metastatic or advanced lung cancer,’ said lead author Dr Patrick Forde, Assistant Professor of Oncology, Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins, Baltimore, US. “This was the first study of neoadjuvant PD-1 blockade in early stage lung cancer.”
“Pneumonitis occurs in approximately 5% of cancer patients treated with anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy agents, according to a new analysis. The complication tends to be low grade and easily resolved, though it can worsen and result in death in rare cases.
“ ‘One of the remarkable characteristics of anti–PD-1/PD-L1 monoclonal antibodies is their relatively mild toxicity profile,’ wrote study authors led by Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center in New York. ‘However, immune-related adverse events can occur and may be severe.’ Pneumonitis is one such immune-related adverse event, and it accounted for several deaths in early trials of these agents.”
“PD-1 inhibitor–related pneumonitis occurred most frequently among patients with non–small cell lung cancer or renal cell carcinoma, according to results of a meta-analysis.
“The incidence of this adverse event also appeared greater during treatment with combination therapy.
“PD-1 inhibitors — including FDA–approved nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck) — are associated with unique toxicities known as immune-related adverse events. Pneumonitis is one such adverse event that, although rare, can be serious and life threatening.”
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As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…