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Phase 2 data for Opdivo (nivolumab) to be presented

Posted: 30 October 2014 | | No comments yet

Phase 2 objective response rate and survival data for Opdivo (nivolumab) in heavily pre-treated advanced squamous cell non-small cell lung cancer to be presented at the 2014 Chicago Multidisciplinary Symposium on Thoracic Oncology…

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Bristol-Myers Squibb Company today 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% 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% (95% 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% (95% CI = 31.6, 49.7) and median overall survival (mOS) was 8.2 months (95% 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% – 18%.1,2

Grade 3-4 drug-related adverse events (AEs) were reported in 17.1% of patients. The most common Grade 3-4 AEs (greater than or equal to 2%) were fatigue (4.3%), pneumonitis (3.4%), and diarrhea (2.6%). Discontinuations due to drug-related AEs 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.

“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.

About the Checkmate -063 Trial Design & Detailed Results

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% receiving greater than or equal to three prior therapies. Seventy-six percent 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% of patients.

With approximately 11 months of minimum follow up, the ORR was 15% (95% 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% (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 AEs were reported in 17.1% of patients. The most common (greater than or equal to 2%) Grade 3-4 AEs were fatigue (4.3%), pneumonitis (3.4%), and diarrhea (2.6%). 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% of patients and there were two drug-related deaths in patients with muliple comorbidities and in the setting of progressive disease.

About Opdivo (nivolumab)

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor 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 program 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 Opdivoin 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, makingOpdivo 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 License 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).

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