On May 14, 2014 Bristol-Myers Squibb reported from a Phase1b study evaluating the safety and efficacy of its investigational PD-1 immune checkpoint inhibitor nivolumab as a single agent in patients with advanced non-small cell lung cancer (NSCLC) who were previously treated (Study -003) and a Phase 1b study evaluating nivolumab as a single agent in chemotherapy-naïve patients (CheckMate -012) (Press release Bristol-Myers Squibb, MAY 14, 2014, View Source [SID:1234500525]). In Study -003, the two-year survival rate was 24% across doses (n=129) for previously-treated patients who received nivolumab as a single agent and highest at 45% in patients who received the 3 mg/kg dose (n=37). In CheckMate -012, the overall response rate (ORR) was 50% in PD-L1 positive tumors and 0% in PD-L1 negative tumors for chemotherapy-naïve patients who received nivolumab as a single agent (n=20). The types of treatment-related serious adverse events (SAEs) in CheckMate -012 were consistent with those in other nivolumab trials with 15% of patients experiencing grade 3-4 treatment-related SAEs. These data will be presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) taking place in Chicago May 30-June 3.

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Results from Phase 1b Single Agent Study in Previously-Treated Patients (Study -003)

Study -003 is a Phase 1b dose escalation study (n=306) evaluating the safety, antitumor activity and pharmacokinetics of nivolumab as a single agent in previously-treated patients with advanced melanoma (n=107), NSCLC (n=129), renal cell carcinoma (n=34), castration-resistant prostate cancer (n=17) or colorectal cancer (n=19). Based on an amendment to the protocol, patients were followed for survival. Eligible patients were administered nivolumab as an intravenous infusion every two weeks of each eight-week treatment cycle. Cohorts of three to six patients per dose level (0.1, 0.3, 1.0, 3.0 or 10 mg/kg) were enrolled sequentially. Patients continued treatment ≤2 years (12 cycles), unless they experienced complete response, unacceptable toxicity, progressive disease or withdrew consent.

Efficacy and safety results from this study were initially presented at ASCO (Free ASCO Whitepaper) and published in the New England Journal of Medicine in 2012. Updated results from the lung cancer cohort, including those shown below, will be presented at ASCO (Free ASCO Whitepaper) on May 31 at 1:15 p.m. CDT (Abstract #8112).

Data to be presented at the 2014 ASCO (Free ASCO Whitepaper) annual meeting, with all patients having greater than or equal to one year of follow up, demonstrated a spectrum, frequency and severity of treatment-related adverse events (AEs) that were consistent with those initially reported in the study at ASCO (Free ASCO Whitepaper) in 2012. Common drug-related AEs included fatigue, decreased appetite, diarrhea, nausea, constipation, cough and dyspnea. Drug-related select AEs with potential immunologic etiologies, defined as adverse events that may require more frequent monitoring and/or unique intervention, included rash, diarrhea and pruritus. These data support the ongoing evaluation of nivolumab as a single agent at the 3 mg/kg dose in patients with previously treated advanced NSCLC in the Phase 3 CheckMate -017 and CheckMate -057 studies.

Results from Phase 1b Study of Chemotherapy-Naïve Patients (CheckMate -012)

CheckMate -012 is a multi-arm Phase 1b trial evaluating the safety and tolerability of nivolumab in patients with chemotherapy-naïve advanced NSCLC, as either a single agent or as part of a regimen with other agents, including in combination with Yervoy (ipilimumab), at different doses and schedules. Secondary outcomes include ORR and progression free survival (PFS). Results from patients who received nivolumab as a single agent, including those shown below, will be presented at ASCO (Free ASCO Whitepaper) on June 3 at 11:30 a.m. CDT (Abstract #8024).

In patients who received nivolumab 3 mg/kg as a single agent (n=20), the objective response rate (ORR) was 50% in patients whose tumors were PD-L1 positive and 0% for tumors that were PD-L1 negative. Responses were observed in both squamous and non-squamous histological subtypes. Median duration of response has not been reach after a median of 15 months of follow up.

After a median of 15 months of follow up, grade 3/4 treatment-related SAEs were reported in 3 patients (15%) and included AST (5%) or ALT (5%) elevations, cardiac failure and hyperglycemia (5%). No pneumonitis (any grade) was observed. These data support the ongoing evaluation of nivolumab as a single agent at the 3 mg/kg dose in the first-line treatment of advanced NSCLC patients in the Phase 3 CheckMate -026 study.

Data from additional arms of CheckMate -012, including nivolumab as part of a regimen with chemotherapy doublets and erlotinib, is also to be presented at ASCO (Free ASCO Whitepaper) 2014 (Abstract #8113, #8022).