Abstract OT2-04-04: Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open label randomized phase 2 trial
Authors: McArthur Heather , Leal Jorge , Page David , Abaya Christina DiLauro , Basho Reva , Ristow Lindsey , Coleman Hannah , Shiao Stephen , Knott Simon , Mita Monica , Tighiouart Mourad , Chung Alice , Dadmanesh Farnaz , McAndrew Philomena , Karlan Scott , Verma Sunil , Giuliano Armando 
Published: March 2020

Abstract
Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, HER2-directed therapy with ICI administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxic backbones; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial, the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are being explored (NCT03747120). Methods: 174 patients (pts) ≥18years with previously untreated, clinical stage II-III, HER2+ breast cancer will be randomized 1:1:1 to one of 3 study arms, stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive THP: T at 80 mg/m2 weekly for 12 weeks, H day 1 at 8 mg/Kg (loading dose) and then 6 mg/Kg every 3 weeks x 3 doses, P day 1 at 840 mg (loading dose) and then 420 mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K day 1 at 200mg (flat dose) and then every 3 weeks x 3 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose of T. After surgery, pts are treated per the treating physician’s discretion including HER2-directed therapy, endocrine therapy and radiotherapy per local clinical standards. The primary endpoint is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity.
Citation Format: Heather McArthur, Jorge Leal, David Page, Christina DiLauro Abaya, Reva Basho, Lindsey Ristow, Hannah Coleman, Stephen Shiao, Simon Knott, Monica Mita, Mourad Tighiouart, Alice Chung, Farnaz Dadmanesh, Philomena McAndrew, Scott Karlan, Sunil Verma, Armando Giuliano. Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open label randomized phase 2 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-04-04.