287TiPNeoadjuvant HER2-targeted therapy with or without immunotherapy with pembrolizumab (neoHIP): An open label randomized phase II trial

AbstractBackgroundImmune 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) is 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). This randomized, multicenter, phase II, open-label trial, will evaluate the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K (NCT03747120).Trial design174 patients (pts) ≥18y with previously untreated, clinical stage II-III, HER2+ breast cancer will be randomized 1:1:1 to one of the 3 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 (TH...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research