Abstract 3042
Background
Anti-PD-1 blockade effectively treats several tumor types. Yet, surrogate biomarkers of clinical benefit are needed to evaluate efficacy, given the delay in observing responses and the existence of pseudo-progressions. This work aims to evaluate serum IL8 levels as a biomarker during anti-PD-1 mAb treatment of melanoma and non-small cell lung cancer (NSCLC) patients.
Methods
44 metastatic melanoma and 19 metastatic NSCLC patients treated with anti-PD-1 mAb therapy as a single-agent, or in combination with anti-CTLA-4 mAb, were studied. Blood was withdrawn at baseline, 2-4 weeks after starting treatment, at best response and at disease progression. Serum IL8 levels were determined by sandwich ELISA. Wilcoxon test was used to compare changes in serum IL8 levels during treatment and the Mann-Whitney U test was used to assess strength of correlation between serum IL8 levels and clinical response assessed by RECIST 1.1 criteria.
Results
The discovery set consisted of 12 melanoma patients treated with anti-PD-1 mAb. In responding patients, serum IL8 levels decreased significantly at the moment of BR compared to baseline levels, and significantly increased upon progression. In non-responders, IL8 levels significantly increased at the moment of progression compared to baseline levels (Table 1). These results were confirmed in a validation set of 17 melanoma and 19 NSCLC patients similarly treated with anti-PD-1 mAbs (Table 1). Additionally, we observed that early changes in serum IL8 levels (2-4 weeks after treatment initiation) strongly correlate with response in the melanoma discovery set (p = 0.05), melanoma validation set (p = 0.001), NSCLC set (p = 0.001) and in a group of 15 melanoma patients treated with anti-CTLA-4 in combination with anti-PD-1 mAbs (p = 0.001).
Responders (clinical setting) | Baseline M (Q1-Q3) pg/ml | Best response M (Q1-Q3) pg/ml | p (baseline vs best response) | Progression M (Q1-Q3) pg/ml | p (best response vs progression) |
---|---|---|---|---|---|
Melanoma (discovery set) | 43.7 (36-49) | 13.6 (5-19) | ConclusionsChanges in serum IL8 levels might be used to monitor and predict response to anti-PD-1 therapy in metastatic melanoma and NSCLC patients. Clinical trial identificationNOT APPLICABLE Legal entity responsible for the studyClinica Universidad de Navarra and Yale University FundingGobierno de Navarra Salud, EU comission IACT and PROCRP, MINECO (SAF2008-03294, SAF2011-22831) DisclosureAll authors have declared no conflicts of interest. Resources from the same session1387 - Active8: A randomized, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with motolimod immunotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neckPresenter: Ezra Cohen Session: Immunotherapy of cancer Resources: Abstract Slides 2980 - Baseline tumor T cell receptor (TcR) sequencing analysis and neo antigen load is associated with benefit in melanoma patients receiving sequential nivolumab and ipilimumabPresenter: Jeffrey Weber Session: Immunotherapy of cancer Resources: Abstract 3047 - Ongoing complete remissions in phase 1 of ZUMA-1: a phase 1-2 multi-center study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in patients with refractory aggressive B cell non-Hodgkin lymphoma (NHL)Presenter: Frederick Locke Session: Immunotherapy of cancer Resources: Abstract Slides Invited discussant abstracts 1047O and 1048OPresenter: Inge-Marie Svane Session: Immunotherapy of cancer Resources: Slides 1880 - A phase 1b study (SCORES) assessing safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of durvalumab combined with AZD9150 or AZD5069 in patients with advanced solid malignancies and SCCHNPresenter: David Hong Session: Immunotherapy of cancer Resources: Abstract 2130 - Combination of MEDI0680, an anti-PD-1 antibody, with durvalumab, an anti-PD-L1 antibody: A phase 1, open-label study in advanced malignanciesPresenter: Omid Hamid Session: Immunotherapy of cancer Resources: Abstract 2428 - Interim safety and clinical activity in patients with advanced NSCLC from a multi-cohort phase 1 study of ramucirumab (R) plus pembrolizumab (P)Presenter: Roy Herbst Session: Immunotherapy of cancer Resources: Abstract 1903 - The MITCI (phase 1b) study: a novel immunotherapy combination of coxsackievirus A21 and ipilimumab in patients with advanced melanomaPresenter: Brendan Curti Session: Immunotherapy of cancer Resources: Abstract Invited discussant abstracts 1049PD, 1050PD, 1051PD and LBA38Presenter: Thomas Powles Session: Immunotherapy of cancer Resources: Slides Webcast 1650 - Phase 1 study of MEDI0562, a humanized OX40 agonist monoclonal antibody (mAb), in adult patients (pts) with advanced solid tumorsPresenter: Bonnie Glisson Session: Immunotherapy of cancer Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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