Durvalumab Plus Tremelimumab Active in Lung Cancer
Durvalumab and tremelimumab demonstrated a manageable tolerability profile and antitumor activity in non-small cell lung cancer.
Similar to how nivolumab plus ipilimumab is used to treat patients with melanoma, a novel immunotherapy combination with durvalumab and tremelimumab demonstrated a manageable tolerability profile and antitumor activity regardless of PD-L1 status in patients with non-small cell lung cancer (NSCLC).1
Researchers hypothesized that durvalumab, an anti-PD-L1 antibody, and tremelimumab, an anti-CTLA-4 antibody, might provide greater antitumor activity than either drug alone, and sought to evaluate the combination in patients with advanced squamous or non-squamous NSCLC.
For the multicenter, open-label, phase 1b study, 102 immunotherapy-naïve patients with confirmed locally advanced or metastatic NSCLC were enrolled. All participants received durvalumab at a dose of 3 mg/kg, 10 mg/kg, 15 mg/kg, or 20 mg/kg every 4 weeks; or 10 mg/kg every 2 weeks, plus tremelimumab at a dose of 1 mg/kg, 3 mg/kg, or 10 mg/kg every 4 weeks for 6 doses, then every 12 weeks for 3 doses.
Researchers determined that the maximum tolerated doses were 20 mg/kg every 4 weeks for darvalumab and 1 mg/kg every 4 weeks for tremelimumab. Results showed that the most common treatment-related grade 3 or 4 adverse events were diarrhea, colitis, and increase lipase; 28% discontinued treatment due to treatment-related adverse events.
Of note, 3 patients died due to treatment: 1 from complications of myasthenia gravis in the durvalumab 10 mg/kg every 4 weeks plus tremelimumab 1 mg/kg group; 1 from pericardial effusion in the durvalumab 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg group; and 1 from a neuromuscular disorder in the durvalumab 20 mg/kg every 4 weeks plus tremelimumab 3 mg/kg group.
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In terms of activity, responses occurred in both patients with PD-L1-positive tumors and in those with PD-L1-negative tumors. The objective response rate was 23% (95% CI, 9 - 44) among the 26 patients who received tremelimumab 1 mg/kg.
The authors noted that durvalumab 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg will be assessed in ongoing phase 3 trials.
- Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study [published online ahead of print February 5, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00544-6.