Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study

Pembrolizumab monotherapy, ipilimumab monotherapy, 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...

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Bibliographic Details
Published in:Clinical cancer research 2018-04, Vol.24 (8), p.1805-1815
Main Authors: Atkins, Michael B, Hodi, F Stephen, Thompson, John A, McDermott, David F, Hwu, Wen-Jen, Lawrence, Donald P, Dawson, Nancy A, Wong, Deborah J, Bhatia, Shailender, James, Marihella, Jain, Lokesh, Robey, Seth, Shu, Xinxin, Homet Moreno, Blanca, Perini, Rodolfo F, Choueiri, Toni K, Ribas, Antoni
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized - administration & dosage
Anticancer properties
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Antitumor activity
Biomarkers, Tumor
Carcinoma, Renal Cell - diagnosis
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - genetics
Carcinoma, Renal Cell - mortality
Dosage
Experimental design
Female
Humans
Immunotherapy
Interferon
Interferon alpha-2 - administration & dosage
Interferon-alpha - administration & dosage
Ipilimumab - administration & dosage
Male
Melanoma
Melanoma - diagnosis
Melanoma - drug therapy
Melanoma - genetics
Melanoma - mortality
Middle Aged
Monoclonal antibodies
Mutation
Neoplasm Metastasis
Neoplasm Staging
Patients
Polyethylene Glycols - administration & dosage
Recombinant Proteins - administration & dosage
Renal cell carcinoma
Targeted cancer therapy
Toxicity
Treatment Outcome
Young Adult
α-Interferon
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Summary:Pembrolizumab monotherapy, ipilimumab monotherapy, 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 Ib KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg every 3 weeks (Q3W) plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6 of 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 to 4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5 of 12 (42%) patients with melanoma and 3 of 10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2 of 14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2 of 3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3 to 4 treatment-related adverse events occurred in 10 of 17 (59%) patients. Responses occurred in 1 of 5 (20%) patients with melanoma and 2 of 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. .
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-17-3436