31 October 2014 - 31 October 2014 - US Bristol-Myers Squibb (NYSE:BMY) disclosed Thursday positive results from CheckMate-063, a Phase II single-arm, open-label trial 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 previous systemic treatments.

The findings will be presented during the Plenary Session at the 2014 Chicago Multidisciplinary Symposium on Thoracic Oncology on October 31 (Abstract #3462).

Checkmate-063 was designed to evaluate 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, and 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 trial's primary goal was objective response rate (ORR) as assessed by an independent review committee (IRC) using RECIST 1.1 criteria. Responders were further characterised by duration of response. Secondary goals included investigator-assessed ORR. Overall survival, PFS and efficacy by PD-L1 expression status were exploratory goals. All treated patients had received at least two previous systemic regimens with 65% receiving greater than or equal to three previous therapies. A total of 76% of patients were within three months of completion of their most recent therapy. The best response to the most recent previous systemic therapy was progressive disease in 61% of patients.

With about 11 months of minimum follow up, the ORR was 15% (95% CI = 8.7, 22.2) as evaluated 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% (95% CI = 31.6, 49.7) and mOS was 8.2 months (95% CI = 6.05, 10.91). An additional 26% of patients had stable disease with a median duration of six months (95% CI, 4.73, 10.91) giving a disease control rate (defined as partial response + stable disease) of 41%. For patients with quantifiable PD-L1 expression, responses were observed independent of PD-L1 status.

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

Dr. Suresh Ramalingam, professor and director of Medical Oncology, Winship Cancer Institute of Emory University, noted that the findings from CheckMate -063 are encouraging as there are currently no effective treatment options for patients with refractory squamous cell lung cancer after their disease has progressed through two previous therapies. Ramalingam said the findings from the study are consistent with Phase I data previously reported from Study -003. He also added that historically, the anticipated one-year survival rate for third-line squamous cell NSCLC patients is about 5.5% - 18%.

Michael Giordano, senior vice president, head of Development, Oncology at Bristol-Myers Squib, said the findings from CheckMate -063 provide further clinical evidence of the potential of immuno-oncology as an innovative approach to treating this disease. He confirmed the company's commitment to addressing the considerable unmet medical needs of patients with lung cancer.

Bristol-Myers Squibb's lung cancer research and development programme is assessing 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 III studies. Four Phase III studies are assessing Opdivo 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 III studies evaluating Yervoy in combination with chemotherapy in newly diagnosed small cell lung cancer (Study -156) and squamous cell NSCLC (Study -104) are currently underway.

Bristol-Myers Squibb has proposed the name Opdivo, which, upon approval from health authorities, will serve as the trademark for nivolumab. In 2013, the US FDA granted Fast Track designation for Opdivo in NSCLC, melanoma and RCC. In April this year, the company started a rolling submission with the FDA for Opdivo in third-line pre-treated squamous cell NSCLC based on CheckMate -063 and anticipates completing the submission by year-end.