Abstract PO1-19-07: A Phase I Study Accessing Immunotherapy Combination of Balstilimab and Ivermectin in Patients with Metastatic Triple Negative Breast Cancer
Authors: Yuan Yuan , Shiao Stephen , Tighiouart Mourad , Mita Monica , Bitar Jin-Sun , McAndrew Philomena , Dorothy Park , El-Masry Maryliza , Frankel Paul , Lee Peter 
Published: May 2024

Abstract
Background: Despite recent FDA approval of immune checkpoint inhibitor (ICI) and antibody-drug conjugates (ADCs), therapeutic options for metastatic triple negative breast cancer (mTNBC) remain limited. There is an unmet need to identify novel ICI combinations for improved efficacy. We recently demonstrated that ivermectin induces robust T cell infiltration into breast tumors and turning “cold” tumors “hot” in mouse model of TNBC. Balstilimab is a fully humanized IgG4 anti-PD-1 agent with proven safety and efficacy in metastatic cervical cancer. The current phase I/II trial is designed to test the safety and efficacy of the combination of ivermectin and balstilimab in patients with mTNBC. Methods: Key eligibility criteria include patients with unresectable or metastatic TNBC; progressed on 1-2 prior chemotherapies including an immune checkpoint inhibitor-containing regimen; ECOG 0-1; RECIST 1.1 measurable disease. Eligible patients receive balstilimab 450 mg, IV, on Day 1 and ivermectin (30, 45 or 60 mg po daily), PO, Days 1-3, 8-10, 15-17 of each 21 days cycle till disease progression or intolerance. The primary objection of the phase 1 portion of the study is t determine the recommended phase 2 dose of ivermectin in combination with balstilimab using NCI-CTCAE v5.0. The primary objective of the phase II portion of the study is to determine the efficacy of the combination in mTNBC who are PD-L1 negative using the objective response rate (ORR). Secondary objectives are progression free survival (PFS), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), and patients’ quality of life (QOL) by EORTC QLQ-C30. Peripheral blood, tumor tissue and gut microbiome will be collected for correlative aims include pharmacokinetics, tumor microenvironment ICDs and gut microbiota in association with response to therapy. In the Phase 1 portion, eligible patients will be enrolled to one of three doses using the IQ 3+3 design. In the Phase 2 portion, patients will continue to be accrued to the RP2D (either the MTD or a lower dose depending on clinical judgement considering all the clinical and correlative data available). The Phase 2 portion will be conducted in two stages. In stage 1, a total of 13 PDL1-negative TNBC breast cancer patients will be treated at the RP2D. If there are no responders, the Phase 2 portion will close. With at least one responder, accrual may continue until 25 patients are accrued to the Phase 2 portion. If at least 3 responders are noted in 25 patients, this will be sufficient to consider the combination promising. This rule provides a type I error of 12% for a true response rate of 5%, and a power of 88% for true response rate of 20%. The estimated targeted accrual is 34-41 (Phase 1: 14-16; Phase 2: 20-25). Clinical trial information: NCT05318469
Citation Format: Yuan Yuan, Stephen Shiao, Mourad Tighiouart, Monica Mita, Jin-Sun Bitar, Philomena McAndrew, Park Dorothy, Maryliza El-Masry, Paul Frankel, Peter Lee. A Phase I Study Accessing Immunotherapy Combination of Balstilimab and Ivermectin in Patients with Metastatic Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-07.