A phase 3 study evaluating second-line therapy with pegilodecakin, a pegylated form of interleukin-10 (IL-10), in combination with FOLFOX compared with FOLFOX alone in patients with metastatic pancreatic adenocarcinoma (PDAC) did not meet its primary endpoint, according to results presented at the 2020 Gastrointestinal Cancers Symposium in San Francisco, California.
IL-10 is an anti-inflammatory cytokine with antitumor activity. Preclinical and early clinical studies of pegilodecakin have shown that it facilitates CD8+ T-cell immunity; these studies provided a rationale for a phase 3 trial evaluating the investigational therapy in combination with FOLFOX chemotherapy in the second line in patients with metastatic PDAC that is refractory to gemcitabine.2,3
In this open-label, phase 3 study (SEQUOIA; ClinicalTrials.gov Identifier: NCT02923921), patients with metastatic disease that progressed following first-line gemcitabine-based therapy were randomly assigned in a 1:1 ratio to receive up to 12 cycles of FOLFOX chemotherapy with or without pegilodecakin. The primary study endpoint was overall survival (OS), with secondary study endpoints including progression-free survival (PFS), objective response rate (ORR), and safety.
Of the 567 patients who were randomly assigned to receive treatment, more than 90% had received first-line therapy with gemcitabine plus nab-paclitaxel.
No significant differences were observed in the median OS of the 2 study arms; OS was 5.8 months for patients treated with FOLFOX plus pegilodecakin vs 6.3 months for those receiving FOLFOX alone (hazard ratio [HR], 1.045; 95% CI, 0.863-1.265; P =.6565).
Similarly, median PFS was 2.1 months in both arms, and the ORR was 4.6% for patients treated with pegilodecakin plus FOLFOX compared with 5.6% for those receiving FOLFOX.
Rates of grade 3 or higher thrombocytopenia (25.2% vs 3.6%), anemia (16.2% vs 4.0%), neutropenia (29.5% vs 22.7%), and fatigue (17.5% vs 10.8%) were higher for patients receiving the pegilodecakin-containing regimen compared with FOLFOX chemotherapy alone.
In summary, the authors reported that the efficacy of second-line FOLFOX for patients with metastatic PDAC was not improved by the addition of pegilodecakin.
Disclosures: This study was funded by Eli Lilly and Company. Some of the authors reported financial relationships with pharmaceutical or medical device companies; for a full list of disclosures, please refer to the study abstract.
- Hecht JR, Lonardi S, Bendell JC, et al. Randomized phase III study of FOLFOX alone and with pegilodecakin as second-line therapy in patients with metastatic pancreatic cancer (SEQUOIA). J Clin Oncol. 2020;38(suppl 4):Abstract 637.
- Naing A, Infante JR, Papadopoulos KP, et al. PEGylated IL-10 (pegilodecakin) induces systemic immune activation, CD8+ T cell invigoration and polyclonal T cell expansion in cancer patients. Cancer Cell. 2018;34(5):775–791.
- Autio K, Oft M. Pegylated interleukin-10: Clinical development of an immunoregulatory cytokine for us in cancer therapeutics. Curr Oncol Rep. 2019;21(2):19.
This article originally appeared on Cancer Therapy Advisor