Pembrolizumab plus pegylated interferon alfa-2b or ipilimumab for advanced melanoma or renal cell carcinoma: dose-finding results from the phase 1b KEYNOTE-029 study

Purpose: Pembrolizumab, ipilimumab, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC. Experimental Design: The phase 1b KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg Q3W plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6/18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients per dose level. Response was assessed per RECIST v1.1 by central review. Results: The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six patients experienced ≥1 DLT. Grade 3-4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5/12 (42%) patients with melanoma and 3/10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2/14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2/3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3-4 treatment-related adverse events occurred in 10/17 (59%) patients. Responses occurred in 1/5 (20%) patients with melanoma and 2/12 (17%) patients with RCC. Conclusions: Pembrolizumab 2 mg/kg Q3W plus ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in patients with advanced melanoma or RCC. The maximum tolerated dose of pembrolizumab plus PEG-IFN had limited antitumor activity in this population.

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