Abstract GS2-06: Phase Ib/II study evaluating safety and efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER2-positive metastatic breast cancer: Results from the PANACEA (IBCSG 45-13/BIG 4-13/KEYNOTE-014) study

Background Preclinical and clinical data suggest that HER2-positive (HER2+) breast cancer (BC) will be amendable to immunotherapeutic approaches. We evaluated pembrolizumab with trastuzumab in patients (pts) with trastuzumab-resistant HER2+, PD-L1 positive (PD-L1pos), unresectable loco-regional or metastatic BC and a parallel cohort of pts with HER2+, PD-L1 negative (PD-L1neg) BC during the phase II study. Methods: Pts with advanced BC and progression on prior trastuzumab-based therapies, ECOG 0-1, and a metastatic tumor biopsy in the last year were eligible. HER2 positivity and quantity of tumor-infiltrating lymphocytes (TILs) on HE proceed if ≥2/17 respond) was used which had 85% power to compare ORR of 7% vs. 22% (1-sided α=0.05). For the PD-L1neg cohort, a single-stage design with 15 pts had u003e95% power to compare ORR of 1% vs. 20% (1-sided α=0.14). Clinicaltrials.gov: NCT02129556. Results: 6 pts enrolled in phase Ib between April and July 2015; no DLTs were observed. The PD-L1pos cohort enrolled 40 pts between August 2015 and September 2016. The PD-L1neg cohort enrolled May 2016 to April 2017, stopping after 12 pts due to low rate of PD-L1 negativity, maintaining u003e90% power to detect the target difference in ORR. PD-L1 testing labs changed in April 2016. Prior to this time, QualTek PD-L1 positive was defined as ≥1% on tumor or TILs. Using the Dako 22C3 antibody, positive was defined as tumor PD-L1 combined positive score (CPS)≥1%. 146 pts were screened to enroll 58 pts. Of screened pts, median stromal TILs was 1% (mean: 4.8%, SD: 9.1%, range: 0 to 60%; n=127); 52% of pts were PD-L1pos, with higher positivity rates while using the Dako assay compared with Qualtek (65% vs. 43%, p=0.009). Median TILs of pts in the PD-L1pos cohort was 2% (mean: 8.1%, SD: 11.2%, range: 0 to 40%) and 0% (mean: 1.2%, SD: 2.2%, range: 0 to 5%) in the PD-L1neg cohort. Of enrolled pts, median age was 51yrs (range: 28-72), 69% had visceral metastases. 29% of pts received prior pertuzumab, 72% had prior T-DM1, 40% prior lapatinib. 38% of pts were ER-positive, 62% were ER-negative. Median TILs in enrolled ER pos and ER neg pts were 1.5% and 2.0%, respectively. PD-L1 positivity rates were also not significantly different by ER status (p=0.5). Final safety data and efficacy results will be presented at the meeting. Citation Format: Loi S, Giobbe-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R, Rabaglio-Poretti M, Kammler R, Maibach R, Smyth MJ, Di Leo A, Colleoni M, Viale G, Regan MM, Andre F. Phase Ib/II study evaluating safety and efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER2-positive metastatic breast cancer: Results from the PANACEA (IBCSG 45-13/BIG 4-13/KEYNOTE-014) study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS2-06.