Abstract P3-09-03: A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study)
Authors: Pérez-García José Manuel , Llombart-Cussac Antonio , Holgado Esther , Curigliano Giuseppe , Miranda Elena López , Alonso-Romero José Luis , Bermejo Begoña , Calvo Lourdes , Carañana Vicente , de la Cruz Sánchez Susana , Cortés María Gión , Vázquez Raúl Márquez , Prat Aleix , Borrego Manuel Ruiz , Sampayo Miguel , Seguí Miguel Àngel , Soberino Jesus , Malfettone Andrea , Schmid Peter , Cortés Javier 
Published: March 2020

Abstract
BACKGROUND: Studies of checkpoint inhibitor monotherapy have shown only modest activity in hormone receptor (HR)-positive (+)/human epidermal growth factor receptor 2 (HER2)-negative (-) metastatic breast cancer (MBC). However, pembrolizumab (P) added to standard neoadjuvant therapy significantly improved the estimated pathologic complete response rate in HR+/HER2- early breast cancer in the I-SPY-2 trial. The KELLY trial aimed to evaluate the efficacy and safety of P in combination with eribulin (E) in anthracycline- and taxane-pretreated patients (pts) with HR+/HER2- inoperable locally recurrent or MBC irrespective of programmed death-ligand 1 (PD-L1) status. METHODS: This is an open-label, single-arm, multicenter phase IIA clinical trial (ClinicalTrials.gov identifier: NCT03222856). Eligible pts had HR+/HER2- inoperable locally recurrent or MBC, who were previously treated with endocrine therapy and at least one, but not more than two, prior chemotherapeutic regimens for treatment of locally recurrent and/or metastatic disease, and with prior anthracycline/taxane exposure either in the early or metastatic setting. Pts received E 1.23 mg/m2 intravenously (IV) on days 1 and 8 with P 200 mg fixed dose IV on day 1 of a 21-day cycle until unacceptable toxicity or disease progression. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints were progression-free survival (PFS), overall response rate (ORR), overall survival (OS), and safety and tolerability of the combination. Exploratory objectives included: (1) the analysis of PFS and ORR based on immune-related RECIST (irRECIST) and (2) the associations of PFS and OS to CBR/ORR, prior exposure to CDK4/6, mTOR, or PI3K inhibitors, PD-L1 status, tumor-infiltrating lymphocytes (TILs), gene signatures, mutational load, and circulating tumor cells. RESULTS: Between January 2018 and October 2018, 44 pts were enrolled in the study. The median age was 54.1 years (range: 46-60.5 years), 70.5% were ECOG 0, 90.1% had visceral disease (86.4% with liver metastases), and 54% with ≥3 involved organ sites. The median number of prior endocrine therapies was two (range: 1-6) and 52.3% of patients had previously received two chemotherapeutic regimens for treatment of locally recurrent and/or MBC. With a median follow-up of 6.64 months (mo.) (range: 1-14.2 mo.), E and P combination met primary endpoint (CBR 53.7%, 95%CI: 36.9-67.3%). ORR and median PFS were 36.4% (95%CI: 22.8-52.3%) and 6.03 mo. (95%CI: 3.7-8.4 mo.), respectively. All-cause adverse events occurred in 100% of pts (G3-4, 56.8%), without treatment-related deaths. ORR and median PFS based on irRECIST were 36.4% (95%CI: 22.8-52.3%) and 6.1 mo. (95%CI: 4.2-8.5 mo.), respectively. OS data are immature (13 deaths, 29.5%). A significant difference in median PFS has been observed between pts with and without clinical benefit (8.5 Vs. 2.2 mo., p&lt;0.001) and responders compared with non-responders (8.3 Vs. 3.4 mo., p=0.024). Previous exposure to CDK4/6, mTOR, or PI3K inhibitors was not associated with differences in PFS (TABLE 1). Updated data, including results about PD-L1 status and TILs will be presented. CONCLUSIONS: E plus P was a safe and active regimen for pts with previously treated HR+/HER2- locally recurrent or MBC that merits further investigation. Exploratory biomarker analysis is pending.
TABLE 1Prior treatmentNEvents (%)Median PFS, mo. (95%CI)p-valueCDK4/6 inhibitorsNo2316 (69.2)6 (3.7-10.4)0.832Yes2115 (71.4)6.1 (2.5-NA)mTOR or PI3K inhibitorsNo2620 (76.9)6 (3.7-8.47)0.727Yes1811 (61.1)6 (2.5-NA)
Citation Format: José Manuel Pérez-García, Antonio Llombart-Cussac, Esther Holgado, Giuseppe Curigliano, Elena López Miranda, José Luis Alonso-Romero, Begoña Bermejo, Lourdes Calvo, Vicente Carañana, Susana de la Cruz Sánchez, María Gión Cortés, Raúl Márquez Vázquez, Aleix Prat, Manuel Ruiz Borrego, Miguel Sampayo, Miguel Àngel Seguí, Jesus Soberino, Andrea Malfettone, Peter Schmid, Javier Cortés. A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study) [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 P3-09-03.