OT1-18-03. The neoIRX trial:locoregional cytokine therapy to promote immunologic priming and enhanced response to neoadjuvant pembrolizumab plus chemotherapy in triple negative breast cancer (TNBC)
Publication Title
San Antonio Breast Cancer Symposium
Document Type
Presentation
Publication Date
12-2021
Keywords
chiles; portland; oregon; california; santa monica; psjmc; newberg
Abstract
Background: In stage II/III TNBC, pembrolizumab when combined with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel [ACT], and carboplatin) improves event free survival and pathologic complete response (pCR) rate (Keynote-522 study).1 Novel combination immunotherapy strategies may further improve outcome and/or afford the opportunity to de-escalate the chemotherapy backbone. We have previously reported safety and feasibility of pre-operative IRX-2, a novel cytokine-based therapeutic that can be administered locoregionally to enhance immune response.2 In a phase Ib study in stage I-III breast cancer, IRX-2 was safe, well tolerated, and associated with increased tumor infiltrating lymphocytes (sTILs, by H&E and multispectral immunofluorescence [mIF]), PD-L1 expression (Ventana SP142 assay, mIF), and lymphocyte activation (by RNA sequencing). These potential immunomodulatory effects support further study of IRX-2 in combination with ICI and chemotherapy in the neoadjuvant setting. Methods: Patients are randomized to a phase II, open-label trial to evaluate the clinical and immunological activity of pembrolizumab plus de-escalated chemotherapy (ACT) when combined with IRX-2 for TNBC. All patients (n=30) will receive pembrolizumab induction (single dose 200mg IV), followed by pembrolizumab every three 3 weeks in conjunction with ACT as neoadjuvant therapy prior to surgery. Patients randomized to arm A (n=15) will additionally receive peri-lymphatic locoregional injections of IRX-2 (1mL SQ x 2 daily, x 10 days) during the induction phase. Eligible subjects will have previously untreated, resectable stage II/III TNBC. The primary endpoint is pCR. The secondary endpoint is safety. On-treatment biopsies following induction (pembrolizumab +/- IRX-2) will permit a prospective, randomized validation of previously reported immunomodulatory effects of IRX-2 (sTILs, PD-L1, lymphocyte RNA signatures). As of 7/8/2021, n=6/30 subjects are enrolled (Providence Cancer Institute, Portland, OR, Providence St. John’s Cancer Institute, Santa Monica, CA, Baylor College of Medicine, Houston, TX). NCT04373031. 1Schmid, P. N Engl J Med 2020; 382:810-821. 2Page, DB. Clin Cancer Res 2020; 26.7:1595-1605
Clinical Institute
Cancer
Clinical Institute
Women & Children
Specialty/Research Institute
Oncology
