Eisai Announces Updated Results of ENHANCE 1, a Phase 1b/2 Trial Investigating HALAVEN® (eribulin mesylate) plus KEYTRUDA® (pembrolizumab) in Patients with Metastatic Triple-Negative Breast Cancer at ASCO 2020

WOODCLIFF LAKE, N.J., May 29, 2020 /PRNewswire/ -- Eisai today announced updated results from ENHANCE 1, a Phase 1b/2 study exploring the investigational combination of eribulin plus pembrolizumab in patients with metastatic triple-negative breast cancer (mTNBC) from a poster discussion session at the American Society of Clinical Oncology's ASCO20 Virtual Scientific Program from May 29-31 (Abstract# 1015 / Poster# 100).

This open-label, single-arm, multicenter, Phase 1b/2 study enrolled patients with mTNBC who had previously received zero to two systemic therapies for metastatic disease and were stratified by prior number of therapy (Stratum 1 = 0 prior therapies; Stratum 2 = 1-2 prior therapies). As there were no dose-limiting toxicities observed in Phase 1, patients received the recommended Phase 2 dose of eribulin (1.4 mg/m(2) intravenously on Day 1 and Day 8) and pembrolizumab (200 mg intravenously on Day 1) of a 21-day cycle. At the time of data cutoff (July 31, 2019), 167 patients were enrolled (of which 149 patients had confirmed PD-L1 status). The primary objectives were safety and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent imaging review. Secondary objectives included progression free survival (PFS), overall survival (OS), duration of response (DOR) and clinical benefit rate (CBR) overall and by PD-L1 status. Previous findings from ENHANCE 1 were presented during a Spotlight Session at the San Antonio Breast Cancer Symposium (SABCS) in 2017.

Updated findings presented during ASCO20 showed:

    --  In the study, no dose-limiting toxicities were observed. Safety
        information is consistent with previous reports.
    --  Of the total patients enrolled (N=167), the combination of eribulin plus
        pembrolizumab resulted in an overall ORR of 23.4% (95% CI: 17.2-30.5),
        the primary efficacy endpoint of the study. The ORR in Stratum 1 (n=66)
        was 25.8% (95% CI: 15.8-38.0), and the ORR in Stratum 2 (n=101) was
        21.8% (95% CI: 14.2-31.1). The overall median PFS was 4.1 months (95%
        CI: 3.5-4.2 months), and the overall median OS was 16.1 months (95% CI:
        13.3-18.5 months), which were secondary endpoints of the study.
    --  In Stratum 1 of patients with confirmed PD-L1 status who received the
        combination of eribulin plus pembrolizumab in the first line (n=60):
        --  ORR was 34.5% (95% CI: 17.9-54.3) in patients with PD-L1+ tumors
            (n=29) and 16.1% (95% CI: 5.5-33.7) in patients with PD-L1- tumors
        --  The median PFS was 6.1 months (95% CI: 4.1-10.2 months) for patients
            with PD-L1+ tumors and 3.5 months (95% CI: 2.0-4.2 months) for
            patients with PD-L1- tumors
        --  The median OS was 21 months (95% CI: 8.3-29.0 months) for patients
            with PD-L1+ tumors and 15.2 months (95% CI: 12.8-19.4 months) for
            patients with PD-L1- tumors
        --  The median DOR was 8.3 months (95% CI: 3.2 months-NE) for patients
            with PD-L1+ tumors and 15.2 months (95% CI: 6.5-22.2 months) for
            patients with PD-L1- tumors
    --  In Stratum 2 of patients with confirmed PD-L1 status who received the
        combination of eribulin plus pembrolizumab in the second line or later
        --  ORR was 24.4% (95% CI: 12.9-39.5) in patients with PD-L1+ tumors
            (n=45) and 18.2% (95% CI: 8.2-32.7) in patients with PD-L1- tumors
        --  The median PFS was 4.1 months (95% CI: 2.1-4.8 months) for patients
            with PD-L1+ tumors and 3.9 months (95% CI: 2.3-6.3 months) for
            patients with PD-L1- tumors
        --  The median OS was 14 months (95% CI: 11.0-19.4 months) in patients
            with PD-L1+ tumors and 15.5 months (95% CI: 12.4-18.7 months) in
            patients with PD-L1- tumors
        --  The median DOR was 8.2 months (95% CI: 5.1-25.1 months) for patients
            with PD-L1+ tumors and 8.6 months (95% CI: 3.5-13.2 months) for
            patients with PD-L1- tumors

The most common treatment-emergent adverse events were fatigue (66%), nausea (57%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). No deaths were considered treatment related. The most common possibly immune-related TEAEs for pembrolizumab (occurring in >3% of patients) were hypothyroidism (18%), pneumonitis (11%), hyperthyroidism (8%) and infusion-related reaction (3%).

"Treatment options for metastatic triple-negative breast cancer remain limited, despite advances in the field," said Dr. Takashi Owa, Vice President, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. "As a human health care company, we are committed to addressing cancers that remain difficult to treat, and this is evident in our ongoing investigation in triple-negative disease. As long as unmet needs exist, Eisai will persist in our efforts to innovate for patients."

This release discusses an investigational use for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

Previously, data from ENHANCE 1 was reported at the San Antonio Breast Cancer Symposium in 2016 and 2017.

The study is being conducted under an existing clinical trial collaboration agreement between Eisai and Merck.

About HALAVEN(® )(eribulin mesylate) Injection
HALAVEN (eribulin mesylate) injection is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Discovered and developed by Eisai, eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. First in the halichondrin class, eribulin is a microtubule dynamics inhibitor. Eribulin is believed to work primarily via a tubulin-based mechanism that causes prolonged and irreversible mitotic blockage, ultimately leading to apoptotic cell death. Additionally, in preclinical studies of human breast cancer, eribulin demonstrated complex effects on the tumor biology of surviving cancer cells, including increases in vascular perfusion resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype, promoting the epithelial phenotype, opposing the mesenchymal phenotype. Eribulin has also been shown to decrease the migration and invasiveness of human breast cancer cells.

Important Safety Information

Warnings and Precautions

Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC. Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome.

Adverse Reactions
In patients with mBC receiving HALAVEN, the most common adverse reactions (>=25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).

Use in Specific Populations
Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

For more information about HALAVEN, click here for the full Prescribing Information.

HALAVEN(®) is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

About Eisai
Eisai is a leading global research and development-based pharmaceutical company headquartered in Japan, with approximately 10,000 employees worldwide. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. We strive to realize our hhc philosophy by delivering innovative products in therapeutic areas with high unmet medical needs, including Oncology and Neurology. In the spirit of hhc, we take that commitment even further by applying our scientific expertise, clinical capabilities and patient insights to discover and develop innovative solutions that help address society's toughest unmet needs, including neglected tropical diseases and the Sustainable Development Goals.

For more information about Eisai, please visit www.eisai.com (for global), us.eisai.com (for U.S.) or www.eisai.eu (for Europe, Middle East, Africa), and connect with us on Twitter (U.S. and global) and LinkedIn (for U.S.).

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