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

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.

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.

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.

 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.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2018 Jan 22 [Epub ahead of print]

Michael B Atkins, F Stephen Hodi, John A Thompson, David McDermott, Wen-Jen Hwu, Donald P Lawrence, Nancy A Dawson, Deborah Jean Lee Wong, Shailender Bhatia, Marihella James, Lokesh Jain, Seth Robey, Xinxin Shu, Blanca Homet Moreno, Rodolfo F Perini, Toni K Choueiri, Antoni Ribas

Lombardi Comprehensive Cancer Center, Georgetown University Medical Center ., Department of Medical Oncology, Dana-Farber Cancer Institute., Med/Onc, University of Washington., Beth Israel Deaconess Medical Center., Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center., Massachusetts General Hospital., Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical System., David Geffen School of Medicine, University of California Los Angeles., Department of Medicine/Medical Oncology, University of Washington Medical Center/Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance., University of Texas MD Anderson Cancer Center., Merck & Co., Inc., Qantitative Pharmacology and Pharmacometrics, Merck & Co., Inc., Oncology, Merck Oncology., Medical Oncology, Dana-Farber Cancer Institute.

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