Background Eganelisib is a first-in-class, oral, selective PI3K-γ inhibitor. Preclinically, eganelisib reprograms macrophages/myeloid derived suppressor cells (MDSCs) from an immune-suppressive to an immune-activating phenotype and enhances efficacy of checkpoint inhibitors. Efficacy of eganelisib + nivolumab in patients with advanced melanoma resistant to immediate prior anti-PD(L)1 therapy is presented.
Methods IPI-549-01 (NCT02637531) evaluates eganelisib in advanced solid tumors, as monotherapy and in combination with nivolumab. The combination expansion dose was eganelisib 40 mg QD PO + nivolumab 240 mg Q2W IV. Combination expansion cohorts include unresectable stage III/IV melanoma patients resistant to immediate prior anti-PD(L)1 therapy. Safety, preliminary clinical activity, PK, and correlative study of blood and tumor biopsy samples were mandated.
Results As of June 1, 2020, 180 patients were treated with eganelisib + nivolumab including 40 with melanoma.The most common (>20% of patients) treatment-emergent adverse events in patients treated with eganelisib + nivolumab (N = 180) were fatigue (34.4%), increased AST (30.0%), increased ALT (26.7%), nausea (25.0%), pyrexia (25.0%), anemia (22.8%), decreased appetite (20.6%), and cough (20.6%). 85 (47.2%) patients experienced at least 1 treatment-emergent serious adverse event (SAE) and 19 (10.6%) had a treatment-related SAE. There was no toxicity unique to the melanoma cohort, and no treatment-related death as assessed by investigators.Preliminary data from the melanoma cohort show that in the efficacy-evaluable population which includes all patients (n=39) who had at least 1 post-baseline response assessment or discontinued treatment due to disease progression, the overall response rate (ORR, ie. CR [complete response] or PR [partial response] per RECIST v1.1) is 7.7%, the disease control rate (DCR, ie. CR, PR, or SD [stable disease]) is 35.9%, and the clinical benefit rate (CBR, ie. CR, PR, or SD of at least 24 weeks from first treatment) is 17.9%, per RECIST v1.1. For patients that received ≤ 2 lines of prior systemic therapy (n=19), the ORR is 15.8%, the DCR is 52.6%, and the CBR is 36.8%. In total, there are 3 patients with PR (duration of response 4–12 months) and 4 with SD > 6 months‘ treatment duration.Translational data evaluating blood MDSCs, cytokines, and proliferation of previously exhausted CD8 memory T-cells as well as changes in immune cell infiltrates from tumor biopsies will be presented.
Conclusions Eganelisib + nivolumab demonstrates an acceptable safety profile and clinical activity in patients with melanoma who were resistant to immediate prior anti-PD(L)1 therapy. Updated clinical and translational data will be presented.
Ethics Approval The study was approved by WIRB, Study Number 1188591 and IRB Tracking Number: 20180297.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.