Abstract PD5-01: KEYNOTE-173: Phase 1b multicohort study of pembrolizumab (Pembro) in combination with chemotherapy as neoadjuvant treatment for triple-negative breast cancer (TNBC)
Authors: Schmid P , Park YH , Muñoz-Couselo E , Kim S-B , Sohn J , Im S-A , Holgado E , Foukakis T , Kuemmel S , Dent R , Yin L , Ding Y , Tryfonidis K , Cortés J 
Published: May 2019

Abstract
Background: TNBC has poor outcome and limited therapeutic options. Pembro monotherapy demonstrated antitumor activity and acceptable safety in metastatic TNBC. KEYNOTE-173 (NCT02622074) is a 6-cohort, phase 1b study of different doses and schedules of platinum and taxanes in combination with pembro as neoadjuvant treatment in patients (pts) with locally advanced TNBC.
Methods: Eligible pts were women aged ≥18 y with newly diagnosed, locally advanced, previously untreated TNBC. In all cohorts, patients received single pembro 200 mg administration on day 1 of cycle 1.Cycles 2-5 included pembro 200 mg with either nab-paclitaxel 125 mg/m2 QW (cohort A), nab- paclitaxel 100 mg/m2 QW plus carboplatin AUC6 Q3W(cohort B), nab-paclitaxel 125 mg/m2 QW plus carboplatin AUC5 Q3W (cohort C), nab- paclitaxel 125 mg/m2 QW plus carboplatin AUC2 QW (cohort D),paclitaxel 80 mg/m2 QW plus carboplatin AUC5 Q3W (cohort E) and paclitaxel 80 mg/m2 QW plus carboplatin AUC2 QW (cohort F) followed by doxorubicin 60 mg/m2 Q3W and cyclophosphamide 600mg/m2 Q3W with pembro 200 mg Q3W in all cohorts (Cycles 6-9) prior to surgery. Breast MRI was performed at screening and after cycles 5 and 9. Dose-limiting toxicities (DLTs) were assessed during cycles 1-3 and 6-7. Dose levels were deemed toxic if ≥3 of the first 6 pts or ≥4 of 10 pts had DLT. Primary end points were safety and recommended phase 2 dose (RP2D). Key efficacy end points were pCR (ypT0/Tis ypN0, or ypT0 ypN0), objective response rate (ORR) based on RECIST v1.1 as assessed by investigator, event-free survival (EFS), and overall survival (OS).
Results: 60 pts were enrolled by 5-31-18 (10/cohort): median age, 48.5 y (range 26-71); most had ductal histology (83.3%), T2/T3 (88.3%) and nodal involvement (66.7%). 22 pts had DLTs (2, A; 4, B/F; 6, C/D); most common was febrile neutropenia (9 pts: 1, A; 2, B/C; 4, D). The most common G≥3 TRAEs were neutropenia (73%), febrile neutropenia (22%), anemia (20%) and thrombocytopenia (8%). 18 pts had immune-related AEs; most common were G2 hypothyroidism (4 pts), G1 hyperthyroidism (3 pts), G3 colitis (2 pts), and G3 rash (2 pts). 11 pts discontinued pembro due to TRAEs (1, A/B/E; 4, D/F). The overall pCR rate (ypT0/Tis ypN0) was 60% (90% CI 30-85). ORR was 100% (74-100) in B/C, 90% (61-100) in D/F, 80% (49-96) in A and 70% (39-91) in E. At a median follow-up of 19.6 mo, EFS rate at 12 mo was 100% in B/C/E/F, 90% (58-98) in D, and 80% (49-93) in A. EFS rate at 12 mo was 100% and 88% for pts who did and did not achieve pCR (71-95).
Conclusion: Pembro+chemo as TNBC neoadjuvant therapy results in promising antitumor activity with manageable toxicity. Results support the ongoing KEYNOTE-522 trial.
Citation Format: Schmid P, Park YH, Muñoz-Couselo E, Kim S-B, Sohn J, Im S-A, Holgado E, Foukakis T, Kuemmel S, Dent R, Yin L, Ding Y, Tryfonidis K, Cortés J. KEYNOTE-173: Phase 1b multicohort study of pembrolizumab (Pembro) in combination with chemotherapy as neoadjuvant treatment for triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD5-01.