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9025 Background: Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Data from a phase II study showed that patients with previously treated advanced melanoma had proportionately more complete/partial responses (CR/PR) and stable disease (SD) with ipilimumab induction 10 mg/kg every 3 weeks (Q3W) X 4 compared with lower doses using the same schedule. Methods: In this randomized, double-blind, multicenter, phase II trial, patients with unresectable stage III/IV melanoma who had progressive disease (PD) on or were intolerant to prior therapies received ipilimumab induction dosing at 0.3, 3, or 10 mg/kg Q3W X 4. Eligible patients received maintenance therapy Q12W starting at Week 24 at their assigned blinded dose. Patients with PD could cross over to open-label ipilimumab 10 mg/kg induction plus maintenance in another study. The primary endpoint was the best overall response rate (BORR CR or PR). Efficacy was measured with modified World Health Organization (mWHO) criteria. Per protocol, tumor evaluation after PD by mWHO (ie, an overall > 25% increase in measurable tumor burden) before treatment with non-ipilimumab neoplastic therapy was permitted. Results: There were 217 patients treated. There was a statistically significant trend indicating an increase in BORR with increasing dose (p = 0.0015). The difference in BORR between 10 and 0.3 mg/kg was 11.2% 95% CI, 3.9 - 18.5. Rates of immune-related adverse events (irAEs) increased with increasing dose. Conclusions: These data favor 10 mg/kg as the optimal dose. 0.3 mg/kg appears to be clinically ineffective. Follow-up for patients is ongoing. Ipilimumab dose (mg/kg) 10 (n = 72) 3 (n = 72) 0.3 (n = 73) BORR - % 95% CI CR - n 11.1 4.9 - 20.7 2 4.2 0.9 - 11.7 0 0 0.0 - 4.9 0 Disease control rate (DCR = PR + CR + SD) - % 95% CI 29.2 19.0 - 41.1 26.4 16.7 - 38.1 13.7 6.8 - 23.8 Any irAE - % 70.4 64.8 26.4 Grade 3/4 irAE - % Any 25.4 7.0 Gastrointestinal 15.5 2.8 0 Hepatobiliary 2.8 0 0 Endocrine 1.4 2.8 0 Skin 4.2 1.4 0 Bowel perforations - % 0 0 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Hamid et al. (Tue,) studied this question.