Pegilodecakin plus anti–PD-1 showed tolerability and efficacy in some advanced solid tumors.

  • Major Finding: Pegilodecakin plus anti–PD-1 showed tolerability and efficacy in some advanced solid tumors.

  • Concept: The best objective response rates were seen in non–small cell lung cancer and renal-cell carcinoma.

  • Impact: Larger, randomized trials of pegilodecakin with pembrolizumab or nivolumab are warranted.


Combination of the anti-inflammatory and CD8+ T-cell stimulating cytokine IL10 with anti–PD-1 therapy has been suggested as a means to increase antitumor activity of both agents. In an open-label, dose-escalation, phase Ib clinical trial, Naing and colleagues investigated treatment of advanced solid tumors with the combination of anti–PD-1 therapies (pembrolizumab or nivolumab) and pegilodecakin, a PEGylated form of IL10 that has a greater in vivo half-life than IL10. In total, 111 patients were enrolled, with 53 being assigned to pembrolizumab plus pegilodecakin (P+P) and 58 being assigned to nivolumab plus pegilodecakin (N+P); most patients had been treated with at least one previous therapy. In the P+P cohort, nine patients had renal-cell carcinoma, five had non–small cell lung cancer (NSCLC), 37 had melanoma, one had bladder cancer, and one had triple-negative breast cancer. In the N+P cohort, 29 patients had renal-cell carcinoma and 29 patients had NSCLC. Six patients died over the course of the trial, though no deaths were determined to be due to study treatment. Toxicity profiles were similar between the cohorts, with 103 (93%) patients experiencing one or more treatment-related adverse events and 73 (66%) experiencing at least one grade 3 or 4 treatment-related adverse event. The most common grade 3 or 4 adverse events were anemia, thrombocytopenia, fatigue, and hypertriglyceridemia. The objective response rate in the 96 evaluable patients was 43% (12 of 28 patients) for NSCLC, 10% (three of 31 patients) for melanoma, and 40% (14 of 35 patients) for renal-cell carcinoma. One patient with NSCLC in the N+P cohort attained a complete response. Pre-specified exploratory analyses of blood samples from a subset of patients receiving pegilodecakin with anti–PD-1 revealed an expansion of T-cell clones after treatment. Limitations of the study include small sample sizes and the absence of comparator groups. Together, the tolerability and efficacy data support continued investigation of the combination of pegilodecakin with anti–PD-1 therapies in larger, randomized trials.

Naing A, Wong DJ, Infante JR, Korn WM, Aljumaily R, Papadopoulos KP, et al. Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial. Lancet Oncol 2019 Sep 25 [Epub ahead of print].

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