Abstract OT1-12-02: Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab

Abstract Background: Probody® therapeutic candidates (Pb-Tx) are masked antibodies designed to be conditionally activated in the tumor microenvironment by tumor-associated proteases. This allows Pb-Tx to address previously undruggable targets that are highly expressed in both tumor and normal tissues. Praluzatamab ravtansine is a masked antibody-drug conjugate targeting CD166 with a DM4 payload. A phase 1 monotherapy study showed safety and durable clinical activity (clinical benefit rate at 24 weeks [CBR24] 28%) in patients (pts) with metastatic HR-positive/HER2 non–amplified breast cancer (mHR+/HER2− BC) or metastatic triple-negative breast cancer (mTNBC). Pacmilimab, a masked PD-L1 inhibitor, demonstrated monotherapy activity in pts with TNBC with an acceptable tolerability profile.Trial design: This phase 2, open-label study with 3 parallel arms (~40 evaluable/arm) will evaluate praluzatamab ravtansine monotherapy (7 mg/kg Q3W) in pts with mHR+/HER2− BC or mTNBC, and praluzatamab ravtansine (7 mg/kg Q3W) combined with pacmilimab (1200 mg Q3W) in pts with mTNBC. Adult pts with an ECOG PS 0–1, measurable disease, and willingness to receive ocular prophylaxis for DM4-related toxicities will be enrolled. Key eligibility criteria for the mHR+/HER2− BC cohort include 2–4 prior regimens in the metastatic setting (excluding single-agent endocrine therapy). No CD166 screening required for HR+/HER2− BC but mTNBC must be CD166+. Pts with mTNBC must have received 1–3 prior metastatic regimens. For mTNBC pts who receive the doublet, key exclusion criteria include known PDL1 negative tumor, history of autoimmune disease, and progression within 120 days of 1st dose of an immuno-oncology agent. Pts with corneal disorders will be excluded. Primary endpoint is overall response rate (ORR) assessed by an independent radiology committee per RECIST v1.1. Secondary endpoints include ORR by investigator, duration of response, CBR16 & 24, progression-free survival, and overall survival. This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with praluzatamab ravtansine as monotherapy and in combination with pacmilimab. This trial is enrolling (NCT04596150). Citation Format: Kathy Miller, Leisha A. Emens, Sara M. Tolaney, Sara A. Hurvitz, Erika Hamilton, Virginia Paton, Alison Hannah, Valentina Boni. Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-02.