The European Commission has approved Bristol-Myers Squibb Company's Nivolumab BMS for the treatment of locally advanced or metastatic squamous (SQ) non-small cell lung cancer (NSCLC) after prior chemotherapy.

This approval marks the first major treatment advance in SQ NSCLC in more than a decade in the European Union (EU). Nivolumab is also the first and only PD-1 immune checkpoint inhibitor to demonstrate overall survival (OS) in previously-treated metastatic SQ NSCLC. This approval allows for the marketing of nivolumab in all 28 member states of the EU.

“With the EU approval of nivolumab, patients in Europe have for the first time in more than ten years access to an entirely new treatment modality for advanced squamous non-small cell lung cancer, which has the potential to replace the current standard of care,” said Emmanuel Blin, senior vice president, head of commercialisation, policy and operations, Bristol-Myers Squibb.

“Bristol-Myers Squibb is passionate about changing survival expectations and the way patients live with advanced cancers, and is committed to continually deliver, with speed and urgency, new approaches to pursue this goal.”

Approval is based on the results of CheckMate -017 and -063. In the phase III CheckMate -017 study, nivolumab demonstrated superior clinical benefit across all endpoints versus docetaxel, the standard of care, regardless of PD-L1 (programmed death ligand-1) expression status, including a 41 per cent reduction in the risk of death, significantly superior OS rate of 42 per cent versus 24 per cent for docetaxel at one-year and superior durable antitumour activity. In the phase II CheckMate -063 study, nivolumab showed an estimated 41 per cent one-year survival rate and a median OS of 8.2 months. The safety profile of nivolumab is consistent with previously-reported trials, and in Checkmate -017, is also favorable compared to docetaxel.

“Today’s approval of nivolumab for squamous non-small cell lung cancer is truly a major advance for patients fighting this devastating disease, and the providers that treat them,” said Rolf Stahel, M.D., president of the European Society of Medical Oncology and professor at University Hospital Zurich. “Nivolumab has shown statistically significant and clinically meaningful improvement in efficacy versus standard of care in this patient population. This approval reinforces the science behind Immuno-Oncology including our understanding of the role of PD-L1 expression.”

In Europe, incidence and mortality rates for lung cancer are on the rise, currently accounting for 20 per cent of all cancer deaths. NSCLC is one of the most common types of the disease and accounts for approximately 85 per cent of lung cancer cases. SQ NSCLC accounts for approximately 25 per cent to 30 per cent of all lung cancers. For patients with NSCLC, whose disease reoccurs or progresses despite chemotherapy, the treatment options are limited and the prognosis is poor, with a five-year survival rate of approximately 2 per cent, globally.

The European Commission’s approval is based on data from two studies (phase III CheckMate -017 and phase II CheckMate -063). Together, the trials investigated nivolumab at a dose of 3 mg/kg every two weeks, which has been well-established across the phase III nivolumab clinical development programme for various tumours.

CheckMate -017 is a landmark phase III, open-label, randomized clinical trial that evaluated nivolumab 3mg/kg intravenously over 60 minutes every two weeks versus standard of care, docetaxel 75 mg/m2 intravenously administered every three weeks in patients with advanced SQ NSCLC who had progressed during or after one prior platinum doublet-based chemotherapy regimen. The study’s primary endpoint was OS and secondary endpoints included progression-free survival (PFS) and overall response rate (ORR). The trial included patients regardless of their PD-L1 expression status.

Results from CheckMate -017 showed a 41 per cent reduction in the risk of death with a one-year survival rate of 42 per cent for nivolumab (42.1 per cent [95 per cent CI: 33.7, 50.3]) versus 24 per cent (23.7 per cent [95 per cent CI: 16.9, 31.1]) for docetaxel (HR 0.59, 96.8 per cent CI: 0.43, 0.81; p=0.0002). Median OS was 9.2 months versus 6 months for nivolumab and docetaxel, respectively. Nivolumab also demonstrated consistent, statistically significant and clinically meaningful improvements across secondary endpoints, ORR and PFS, versus docetaxel in patients with previously treated advanced SQ NSCLC. Survival benefit was observed independent of PD-L1 expression across all pre-specified expression levels (1per cent , 5 per cent and 10 per cent ).

The safety profile of nivolumab in CheckMate -017 was consistent with prior studies and favourable versus docetaxel. Treatment-related adverse events (AEs) occurred less frequently with nivolumab (any grade, 58 per cent ; grade 3-4, 6.9 per cent; no grade 5 events) than docetaxel (any grade, 86 per cent; grade 3-5, 55 per cent, grade 5, 2.3 per cent), including both haematology and non-haematology toxicities. Treatment-related AEs led to discontinuation in 3.1 per cent of patients in the nivolumab arm compared to 10.1 per cent for docetaxel. Pneumonitis (1.5 per cent ) was the most common treatment-related AE leading to discontinuation in the nivolumab arm and peripheral neuropathy (3.1 per cent) for the docetaxel arm.

Findings from CheckMate -017 were recently published in The New England Journal of Medicine and presented during an oral abstract session at the 2015 American Society of Clinical Oncology Annual Meeting in May 2015.

CheckMate -063 is a phase II, single-arm, open-label trial that included patients with metastatic SQ NSCLC who had progressed after two or more lines of therapy. In this trial, the confirmed objective response rate by an independent radiology review committee, the study’s primary endpoint, was 14.5 per cent (95 per cent CI: 8.47, 22.2) with an estimated one-year survival rate of 41 per cent and median OS of 8.21 months (95 per cent CI: 6.05, 10.9). The safety profile of nivolumab in CheckMate -063 was consistent with prior clinical studies and managed using established treatment algorithms.

Bristol-Myers Squibb submitted two separate marketing authorisation applications, one in advanced melanoma under the tradename Opdivo and one for SQ NSCLC under the Nivolumab BMS trade name in order to accelerate availability of nivolumab for health care professionals in both indications. The goal is to have these two marketing authorisations “reconciled” into a single marketing authorisation, under the Opdivo brand name toward the end 2015.

Bristol-Myers Squibb has a broad, global development program with over 8,000 patients enrolled in more than 50 trials evaluating nivolumab across multiple tumor types – as monotherapy or in combination with other therapies.

Nivolumab is the first PD-1 immune checkpoint inhibitor to receive regulatory approval on July 4, 2014 when Ono Pharmaceutical Co. announced that it received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma. On December 22, 2014, the US Food and Drug Administration (FDA) granted its first approval for nivolumab for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. On March 4, 2015, nivolumab received its second FDA approval for the treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. The European Commission announced approval of nivolumab on June 19, 2015, for the treatment of advanced (unresectable or metastatic) melanoma in adults, regardless of BRAF status.

The most common adverse reactions (20 per cent) reported with OPDIVO in trial 1 were rash (21 per cent)) and in trial 3 were fatigue (50 per cent)), dyspnea (38 per cent)), musculoskeletal pain (36 per cent), decreased appetite (35 per cent), cough (32 per cent), nausea (29 per cent), and constipation (24 per cent).

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year, according to the World Health Organisation. NSCLC is one of the most common types of the disease and accounts for approximately 85 per cent of cases. Survival rates vary depending on the stage, histology and sub-type of lung cancer. The majority of NSCLC patients have advanced stage disease at the time of diagnosis. Globally, the five-year survival rate for stage I NSCLC is between 47 and 50 per cent; for stage IV NSCLC, the five-year survival rate drops to two per cent.

Lung cancer has the highest economic burden of all cancers in the European Union, costing an estimated €18.8 billion or 15 per cent of overall cancer costs.

Bristol-Myers Squibb is a global pharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.