Bristol-Myers Squibb Company announced results from CheckMate -063, a phase 2 single-arm, open-label study of Opdivo (nivolumab), an investigational PD-1 immune checkpoint inhibitor, administered as a single agent in patients with advanced squamous cell non-small cell lung cancer (NSCLC) who have progressed after at least two prior systemic treatments with 65 per cent receiving three or more prior therapies (n=117). With approximately 11 months of minimum follow up, the objective response rate (ORR, the study’s primary endpoint) was 15 per cent (95 per cent CI = 8.7, 22.2) as assessed by an independent review committee (IRC) using RECIST 1.1 criteria and the median duration of response was not reached. The estimated one-year survival rate was 41 per cent (95 per cent CI = 31.6, 49.7) and median overall survival (mOS) was 8.2 months (95 per cent CI = 6.05, 10.91). These data will be presented during the Plenary Session at the 2014 Chicago Multidisciplinary Symposium on Thoracic Oncology on October 31 (Abstract #3462).

“The phase 2 findings from CheckMate -063 are encouraging as there are no effective treatment options for patients with refractory squamous cell lung cancer after their disease has progressed through two prior therapies,” said Suresh S. Ramalingam, MD, Professor and Director of Medical Oncology, Winship Cancer Institute of Emory University. “The results are also consistent with Phase 1 data previously reported from Study -003.” Historically, the expected one-year survival rate for third-line squamous cell NSCLC patients is approximately 5.5 per cent - 18 per cent.1,2

Grade 3-4 drug-related adverse events (AEs) were reported in 17.1 per cent of patients. The most common Grade 3-4 AEs (greater than or equal to 2 per cent) were fatigue (4.3 per cent), pneumonitis (3.4 per cent), and diarrhea (2.6 per cent). Discontinuations due to drug-related AEs of any grade occurred in 12 per cent of patients and there were two drug-related deaths in patients with multiple comorbidities and in the setting of progressive disease.

“Results from CheckMate -063 offer further clinical evidence of the potential of immuno-oncology as an innovative approach to treating this disease,” said Michael Giordano, senior vice president, Head of Development, Oncology. “We are committed to addressing the significant unmet medical needs of patients with lung cancer and have the broadest development program evaluating our approved and investigational immuno-oncology agents across multiple lines of therapy and histology.”

Bristol-Myers Squibb’s lung cancer research and development program is evaluating its approved and investigational immunotherapies either as single agents or as part of combination regimens across lines of therapy, histologies and biomarker expression. Among these are six ongoing phase 3 trials. Four phase 3 trials are evaluating Opdivo (nivolumab) as a single agent three in previously treated patients (CheckMate -017, CheckMate -057 and CheckMate -153 ) and one in chemotherapy-naïve patients (CheckMate -026). Two phase 3 trials evaluating Yervoy in combination with chemotherapy in newly diagnosed small cell lung cancer (Study -156) and squamous cell NSCLC (Study -104) are ongoing.

Bristol-Myers Squibb has proposed the name Opdivo (pronounced op-dee-voh), which, if approved by health authorities, will serve as the trademark for nivolumab.

Checkmate -063 is a phase 2 single arm, open-label study designed to assess advanced squamous cell NSCLC patients who progressed after both platinum-based therapy and at least one additional systemic therapy with an ECOG Performance Status of 0 or 1 who were treated with Opdivo as a single agent 3mg/kg by intravenous infusion every two weeks until disease progression or treatment discontinuation (n=117). The primary endpoint was ORR as assessed by an IRC using RECIST 1.1 criteria. Responders were further characterized by duration of response. Secondary endpoints included investigator-assessed ORR. Overall survival, PFS and efficacy by PD-L1 expression status were exploratory endpoints. All treated patients had received at least two prior systemic regimens with 65 per cent receiving greater than or equal to three prior therapies. Seventy-six per cent of patients were within three months of completion of their most recent therapy. The best response to the most recent prior systemic therapy was progressive disease in 61 per cent of patients.

With approximately 11 months of minimum follow up, the ORR was 15 per cent (95 per cent CI = 8.7, 22.2) as assessed by an IRC using RECIST 1.1 criteria and the median duration of response was not reached. The estimated one-year survival rate was 41 per cent (95 per cent CI = 31.6, 49.7) and mOS was 8.2 months (95 per cent CI = 6.05, 10.91). An additional 26 per cent of patients had stable disease with a median duration of six months (95 per cent CI, 4.73, 10.91) giving a disease control rate (defined as partial response + stable disease) of 41 per cent. For patients with quantifiable PD-L1 expression, responses were observed independent of PD-L1 status.

Grade 3-4 drug-related AEs were reported in 17.1 per cent of patients. The most common (greater than or equal to 2 per cent) Grade 3-4 AEs were fatigue (4.3 per cent), pneumonitis (3.4 per cent), and diarrhoea (2.6 per cent). Drug-related AEs generally were manageable with corticosteroids and/or supportive care as per established safety algorithms. Discontinuations due to drug-related AEs of any grade occurred in 12 per cent of patients and there were two drug-related deaths in patients with multiple comorbidities and in the setting of progressive disease.

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumour from immune attack. Opdivo is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells.

Bristol-Myers Squibb has a broad, global development programme to study Opdivo in multiple tumor types consisting of more than 35 trials as monotherapy or in combination with other therapies in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in NSCLC, melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma.

In 2013, the FDA granted Fast Track designation for Opdivo in NSCLC, melanoma and RCC. In April 2014, the company initiated a rolling submission with the FDA for Opdivo in third-line pre-treated squamous cell NSCLC based on CheckMate -063 and expects to complete the submission by year-end. The FDA granted Opdivo Breakthrough Therapy Designation in May 2014 for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab. On July 4, Ono Pharmaceutical Co. announced that Opdivo received manufacturing and marketing approval in Japan for the treatment of patients with unresectable melanoma, making Opdivo the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. On September 26, Bristol-Myers Squibb announced that the FDA accepted for priority review the  Biologics Licence Application for previously treated advanced melanoma, and the Prescription Drug User Fee Act (PDUFA) goal date for a decision is March 30, 2015. The FDA also granted Opdivo Breakthrough Therapy status for this indication. In the  European Union, the European Medicines Agency (EMA) has validated for review the Marketing Authorization Application (MAA) for  Opdivo in advanced melanoma and lung cancer. The advanced melanoma application has also been granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use (CHMP).

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year according the World Health Organization. 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 and type of the cancer when it is diagnosed. 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 percent. Historically, the expected one-year survival rate for third-line squamous cell NSCLC patients is approximately 5.5 per cent 18 per cent.

Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease.

To address this unmet medical need, Bristol-Myers Squibb is leading advances in the innovative field of immuno-oncology, which involves agents whose primary mechanism is to work directly with the body’s immune system to fight cancer. The company is exploring a variety of compounds and immunotherapeutic approaches for patients with different types of cancer, including researching the potential of combining immuno-oncology agents that target different and complementary pathways in the treatment of cancer.

Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialise Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono Pharmaceutical further expanded the companies’ strategic collaboration agreement to jointly develop and commercialise multiple immunotherapies as single agents and combination regimens for patients with cancer in Japan, South Korea and Taiwan.