Immunologic and tumor responses of pegilodecakin with 5-FU/LV and oxaliplatin (FOLFOX) in pancreatic ductal adenocarcinoma (PDAC)
- 10 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 39 (1), 182-192
- https://doi.org/10.1007/s10637-020-01000-6
Abstract
Summary Background Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited and checkpoint blockade inhibitors have been disappointing in this disease. Pegilodecakin has demonstrated single agent anti-tumor activity in immune-sensitive tumors. Phase 1 and preclinical data indicate synergy of pegilodecakin with 5-FU and platins. We assessed the safety and activity of pegilodecakin+FOLFOX in patients with PDAC. Methods IVY (NCT02009449) was an open-label phase 1b trial in the United States. Here we report on all enrolled patients from cohort C. Heavily pretreated patients were treated with pegilodecakin (self-administered subcutaneously daily at 2.5, 5, or 10 μg/kg) + 5-flurouracil/leucovorin/oxaliplatin (FOLFOX), dosed per manufacturers prescribing information, until tumor progression. Eligible patients had measurable disease per immune-related response criteria (irRC), were ≥ 18 years of age, and had ECOG performance status of 0 or 1. Patients were evaluated for primary(safety) and secondary (tumor response per irRC) endpoints. Results From 5 August 2014–12 July 2016, 39 patients enrolled in cohort C. All patients were evaluable for safety. In this advanced population, regimen had manageable toxicities with no immune-related adverse events (irAEs) greater than grade 1. The most common grade 3/4/5 TEAEs were thrombocytopenia (21[53.8%] of 39) and anemia (17[43.6%] of 39). In evaluable PDAC patients, the best overall response of pegilodecakin+FOLFOX was 3(14%) with CRs in 2(9%) patients. Conclusions Pegilodecakin+FOLFOX had an acceptable tolerability profile in PDAC, with no substantial irAEs seen, and promising efficacy with the combination yielding a 2-year OS of 24% (95% CI 10–42). These data led to the phase 3 study with pegilodecakin+FOLFOX as second-line therapy of PDAC (SEQUOIA).Keywords
Funding Information
- Eli Lilly and Company (none)
This publication has 28 references indexed in Scilit:
- Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid TumorsClinical Cancer Research, 2015
- Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 TrialJournal of Clinical Oncology, 2014
- FOLFOX as second-line chemotherapy in patients with pretreated metastatic pancreatic cancer from the FIRGEM studyBMC Cancer, 2014
- IL-10: Master Switch from Tumor-Promoting Inflammation to Antitumor ImmunityCancer Immunology Research, 2014
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerThe New England Journal of Medicine, 2012
- XELOX versus FOLFOX4 as Second Line Chemotherapy in Advanced Pancreatic CancerHepato-Gastroenterology, 2012
- IL-10 Elicits IFNγ-Dependent Tumor Immune SurveillanceCancer Cell, 2011
- FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic CancerThe New England Journal of Medicine, 2011
- Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response CriteriaClinical Cancer Research, 2009
- Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-α expressionPain, 1998