Abstract PS11-32: Mario-3 phase II study safety run-in evaluating a novel triplet combination of eganelisib (formerly IPI-549), atezolizumab (atezo), and nab-paclitaxel (nab-pac) as first-line (1L) therapy for locally advanced or metastatic triple-negative breast cancer (TNBC)
Authors: Hamilton Erika , Lee Arielle , Swart Rachel , Newton Gina , O'Connell Brenda , Roberts Jennifer , Zhang Halle , Soliman Hatem 
Published: February 2021

Abstract
Purpose: The IMpassion130 randomized trial in advanced TNBC has demonstrated improved efficacy with the addition of atezo to 1L nab-pac in patients with PD-L1+ tumors. Eganelisib is a first-in-class, novel oral agent targeting tumor-associated myeloid cells through selective inhibition of PI3K-gamma, with the goal of improving the immune response to the approved doublet combination of atezo and nab-pac. We report first results from a completed TNBC safety run-in cohort of a multicenter phase II study.
Methods: Eligible patients had measurable unresectable locally advanced or metastatic TNBC, ECOG performance status 0/1, and no prior systemic therapy for advanced disease. A safety run-in was completed to assess the safety of the triplet of oral eganelisib 30 mg daily in combination with nab-pac 100 mg/m2 given on days 1, 8, & 15, and IV atezo 840 mg given on days 1 & 15. After establishing tolerability in the safety run-in (n=6), the expansion phase of the phase II study was initiated to enroll a total of approximately 60 patients (30 PD-L1+ and 30 PD-L1-). Cycles are repeated every 28 days until loss of clinical benefit, unacceptable toxicity, or consent withdrawal. The primary efficacy endpoint is confirmed Complete Response (CR) rate per RECIST v1.1. Secondary endpoints include the overall response rate (ORR) and safety assessment. Tumors are assessed every 8 weeks by CT/MRI scan.
Results: We report preliminary efficacy data (as of 6/27/2020) and safety data (as of 6/09/2020) for the completed safety run-in cohort with 6 patients evaluable for safety and 4 evaluable for response defined as having had at least one post-baseline tumor assessment. 1 CR (1/4) and 3 PRs (3/4) were observed with an ORR of 100% (4/4). Responses were seen irrespective of PD-L1 status. The most common all-grade adverse events were decreased white cell count (66.7%), fatigue (50%), diarrhea (33.3%), hyperglycaemia (33.3%), transaminase elevation (16.7%), pyrexia (16.7%), and rash (16.7%). Most common grade ≥3 adverse events occurred in 3 patients (50%) including decreased lymphocytes or neutropenia (33.3%), transaminase elevation (16.7%), fatigue (16.7%), rash (16.7%), and febrile neutropenia (16.7%). Treatment was generally tolerable. Eganelisib 30 mg daily was chosen as the dose for combination with nab-pac and atezo for the expansion phase of the study.
Conclusions: The novel triplet regimen of eganelisib, atezo, and nab-pac shows promising antitumor activity (4 responses/4 evaluable patients), irrespective of biomarker status, and has manageable toxicity. The expansion phase of the phase II study is currently enrolling. Updated efficacy, safety and biomarker data will be presented for the safety run-in cohort as well as initial data from the expansion phase of the phase II study.
Citation Format: Erika Hamilton, Arielle Lee, Rachel Swart, Gina Newton, Brenda O'Connell, Jennifer Roberts, Halle Zhang, Hatem Soliman. Mario-3 phase II study safety run-in evaluating a novel triplet combination of eganelisib (formerly IPI-549), atezolizumab (atezo), and nab-paclitaxel (nab-pac) as first-line (1L) therapy for locally advanced or metastatic triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-32.