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).”


OK for Flu Shot With Nivolumab, Other Checkpoint Inhibitors?

“The cancer treatment strategy of immune checkpoint blockade has produced unprecedented results in melanoma and lung cancer, as well as in experimental settings with other tumor types, including renal cell carcinoma and mesothelioma.

“Clinicians are not alone in taking notice, according to Niesha Griffith, MS, RPh, a pharmacist at the James Cancer Hospital of The Ohio State University in Columbus.

“Multiple patients at her center have requested these drugs for off-label use, and offered to pay upfront and out-of-pocket for the expensive therapies, she said. Such offers were rare before the advent of cancer immunotherapy, but now occur regularly.”


Nivolumab Improves the Proportion of Lung Cancer Patients Alive After More than a Year

“Patients with a type of lung cancer called non-squamous non-small cell lung cancer (non-SQ NSCLC) have limited treatment options and a dismal prognosis once their disease has advanced and initial treatment with platinum-based chemotherapy has failed. Second-line treatment is usually with another chemotherapy drug, such as docetaxel or pemetrexed.

“Recent results have shown that the drug, nivolumab, improves survival for these and now updated results from the CheckMate 057 phase III clinical trial, to be reported at the 2015 European Cancer Congress today (Monday) with simultaneous publication of the study results in the New England Journal of Medicine, show that nivolumab continues to show an overall survival benefit compared to . Among patients randomised to receive nivolumab, significantly more were alive at 12 months compared to those treated with docetaxel – 51% versus 39% respectively – and a difference in survival remains at 18 months – 39% for nivolumab versus 23% for docetaxel.

“This improvement in survival was observed for all patients included in the trial, but nivolumab was more effective in patients whose tumours expressed a protein called programmed death ligand 1 (PD-L1), which plays a role in the immune system’s ability to recognise and attack tumours and has been correlated with response to immune checkpoint inhibitors such as nivolumab.”


NivoPlus Clinical Trial Currently Recruiting Patients With Advanced Cancer

“The Cancer Treatment Centers of America (CTCA) at Western Regional Medical Center in Arizona recently started a Phase Ib/II clinical trial called NivoPlus (NCT02423954) to test a new investigational immunotherapeutic treatment for several advanced cancers. This novel immunotherapeutic approach is based on the combination of an immunotherapy drug (nivolumab) with chemotherapy drugs (irinotecan, temsirolimus and a combination of irinotecan and capecitabine) which have been approved by the U.S. Food and Drug Administration (FDA).

“Cancer immunotherapy is defined as the use of the body’s own immune system to help fight cancer. In 2013, the renowned Science magazine established that cancer immunotherapy had been the scientific breakthrough of the year, and recent advances in the field have yielded promising results for cancer patients.

“Nivolumab is an antibody against the programmed death 1 (PD-1) receptor, an immune checkpoint that if inhibited results in the stimulation of the body’s antitumor immunity. Nivolumab has been approved by the FDA for the treatment of advanced melanoma in December 2014 and metastatic squamous non-small cell lung cancer in March 2015. Its combination with chemotherapeutic drugs is expected to activate the body’s immune system and improve the response to cancer.”


Melanoma at ASCO 2015: Immunotherapy Continues to Make Headlines


The biggest news in melanoma treatment from the 2015 American Society of Clinical Oncology (ASCO) annual meeting was undoubtedly the report from a large, phase III, randomized clinical trial that compared a combination of two ‘checkpoint inhibitor’ drugs—nivolumab (Opdivo) and ipilimumab (Yervoy)—with the same drugs given alone.

In the CheckMate-067 trial, 945 previously untreated patients with unresectable stage III or IV melanoma were assigned to Opdivo alone, Opdivo plus Yervoy, or Yervoy alone. Continue reading…


Small Cell Lung Cancer at ASCO: Some Welcome News


Small cell lung cancer (SCLC) is a fatal disease that has not seen new drug approvals for the last 17 years. Considering the relative success of ‘immune checkpoint inhibitors’ in non-small cell lung cancer (NSCLC), it is not surprising that several abstracts recently presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting were devoted to clinical trials testing these trendy, immune system-boosting drugs in people with SCLC. Continue reading…


AstraZeneca and Lilly to Collaborate on Immuno-Oncology Combination Clinical Trial in Solid Tumours

“AstraZeneca and Eli Lilly and Company (Lilly) today announced that they have entered into a clinical trial collaboration to evaluate the safety and preliminary efficacy of AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, MEDI4736, in combination with ramucirumab (CYRAMZA®), Lilly’s VEGF Receptor 2 antiangiogenic cancer medicine. The planned study will assess the combination as a treatment for patients with advanced solid tumours.

“The Phase I study is expected to establish the safety and a recommended dosing regimen, with the potential to open expansion cohorts in various tumours of interest, for the combination of MEDI4736 and ramucirumab. Under the terms of the agreement, the trial will be sponsored by Lilly. Additional details of the collaboration, including tumour types to be studied and financial terms, were not disclosed.”


Immune Checkpoint Inhibitors in Melanoma: New Directions


The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…


More on the Use of Nivolumab and Ipilimumab in Melanoma

“As single agents, immune checkpoints blockers nivolumab (Opdivo) and ipilimumab (Yervoy) both have demonstrated improvements in overall survival for patients with metastatic melanoma. However, when taken together, these agents have demonstrated even more impressive findings.

“Earlier reported findings from a phase I dose-escalation study demonstrated that the combination of the PD-1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab demonstrated encouraging antitumor activity. Additionally, an ongoing phase III clinical trial is assessing nivolumab or ipilimumab plus nivolumab versus ipilimumab alone in previously untreated patients with advanced melanoma (CheckMate-067; NCT01844505).

“At the 2015 AACR Annual Meeting, F. Stephen Hodi, MD, presented findings from the phase II CheckMate-069 trial, further validating the efficacy seen with the combination in earlier studies and providing hints at what could be expected in the phase III trial. In this analysis, nivolumab plus ipilimumab delayed disease progression by 60% compared with 11% in patients who were given ipilimumab alone (HR = 0.40; 95% CI, 0.23-0.68; P .001). With the combination, the ORR was 61% in BRAF wild-type (WT) patients and 52% in BRAF-positive patients.

“Included in the phase II CheckMate-069 study were 142 treatment-naïve patients with advanced melanoma with a median patient age of 65 years. Patients were randomized to receive ipilimumab at 3 mg/kg with either nivolumab at 1 mg/kg (n = 95) or placebo (n = 47) every 3 weeks for four doses. This was followed by nivolumab or placebo every 2 weeks until progression or unacceptable toxicity.”