Encouraging Updated Results from Phase 1b/2 Study Evaluating the Combination of Eribulin Mesylate and Pembrolizumab in Patients with Metastatic Triple-Negative Breast Cancer Presented at the 2017 SABC

Hatfield, England (ots/PRNewswire) -

Eisai today announced updated results of ENHANCE 1, a Phase 1b/2
trial investigating eribulin mesylate (Halaven®), in combination with
the Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside of
the United States and Canada) anti-PD-1 therapy, pembrolizumab
(marketed as KEYTRUDA®), in patients with metastatic triple-negative
breast cancer (mTNBC).[1] Findings presented during the 2017 San
Antonio Breast Cancer Symposium (SABCS) showed the combination of
eribulin and pembrolizumab resulted in an objective response rate
(ORR) of 26.4% (95% CI: 18.3 - 35.9), the primary efficacy endpoint
of the study.[1] Three complete responses were observed; one of which
was in a patient with a PD-L1-negative tumour.[1] Treatment-emergent
adverse events (TEAEs) for the combination regimen were comparable to
those observed with each treatment as a monotherapy.[1] Eribulin and
pembrolizumab are not approved for use in combination.

"The results observed, namely the response rates and tolerability
achieved with the eribulin and pembrolizumab combination regimen,
broaden our knowledge base as to the possible effect of these two
agents when used together in patients with metastatic TNBC," said
Sara Tolaney, MD, MPH, medical oncologist, Dana-Farber Cancer
Institute, Boston, and the principal investigator of the study. "The
potential of the combination of eribulin plus pembrolizumab for this
aggressive form of breast cancer is exciting for both patients and
physicians alike."

The combination of eribulin and pembrolizumab demonstrated
activity in patients with mTNBC regardless of PD-L1 status or prior
treatment with chemotherapy.[1] In the evaluable analysis set
(n=106), patients who were PD-L1-positive (n=49) had an ORR of 30.6%
and patients who were PD-L1-negative (n=49) had an ORR of 22.4%.
Patients with mTNBC who had no prior chemotherapy treatment in the
metastatic setting (n=65) had an ORR of 29.2% (95% CI: 18.6 - 41.8)
and patients who received one or two prior lines of chemotherapy
(n=41) had an ORR of 22.0% (95% CI: 10.6 - 37.6).[1] The median
duration of response was 8.3 months (6.5 - 12.9) and the response
lasted longer than six months in 53.6% of responders.[1] The clinical
benefit rate (CBR, complete response + partial response + durable
stable disease [duration greater than or equal to 24 weeks]) was
36.8%.[1] Median overall survival and median progression-free
survival for all patients in the trial (the full analysis set;
n=107), both secondary endpoints, were 17.7 months (95% CI: 13.7 -
not estimable) and 4.2 months (95% CI: 4.1 - 5.6), respectively.[1]

The most common treatment-emergent adverse events (TEAEs) for the
combination regimen were fatigue, peripheral neuropathy, nausea,
alopecia, and constipation.[1] The most common grade 3 or 4 TEAEs for
the combination regimen were neutropaenia, peripheral neuropathy, and
anaemia, fatigue, and hypokalaemia. Dose reduction due to TEAEs
occurred in 32% of patients. Drug withdrawal due to TEAEs occurred in
22% of patients.[1]

"Most of the major advances in breast cancer treatment to date
have been for patients whose cancers express the receptors currently
identified as targets for treatment; limited options exist for
patients with metastatic triple-negative breast cancer," said Alton
Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer,
Oncology Business Group at Eisai. "These updated results give us
confidence to continue to study eribulin in the treatment of
metastatic breast cancer in combination with new agents, like
checkpoint inhibitors. We are very encouraged by the activity seen
when adding pembrolizumab to eribulin, and we are eager to further
assess these data and their meaning for patients with metastatic
TNBC."

Eisai will also be presenting data from Study 216, a Phase 2 trial
evaluating a biweekly dosing schedule of eribulin in patients with
human epidermal growth factor receptor 2 (HER2)-negative metastatic
breast cancer (Poster Session 6: PD-14-05, Saturday 9 December)[2]
and results from a study in TNBC evaluating the effect of eribulin on
the TGF-? signalling pathway in two different preclinical breast
cancer cell lines (Poster Session 5: P5-04-04, Friday 8 December).[3]

Eisai is dedicated to the discovery, development and production of
innovative oncology therapies that can make a difference and impact
the lives of patients and their families. This passion for people is
part of Eisai's human health care (hhc) mission, which strives to
better understand the needs of patients and their families to
increase the benefits health care provides.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp.,
a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Notes to Editors

About ENHANCE 1 (Also referred to as KEYNOTE-150; formerly
referred to as Study 218)[1]

ENHANCE 1 is a single-arm, multi-centre Phase 1b/2 study
(ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02513472)
Identifier: NCT02513472) investigating the combination of
pembrolizumab (200 mg intravenously on Day 1) with eribulin mesylate
(1.4 mg/m2 intravenously on Day 1 and Day 8) in 21-day cycles in
patients with metastatic TNBC who had previously been treated with up
to two lines of chemotherapy or were not previously treated with
chemotherapy.[1] At the time of data cutoff (May 31, 2017), 107
subjects were enrolled, 106 of whom were evaluable.[1] The primary
endpoint of the Phase 1b portion of the study is to assess the safety
and tolerability of the combination; for the Phase 2 portion of the
study, the primary endpoint is investigator-assessed ORR and
secondary endpoints include progression-free survival, overall
survival and duration of response as well as efficacy in a subset of
patients with PD-L1-positive tumours.[1]

The results presented at 2017 SABCS were an updated analysis from
the poster presentation "Phase 1b/2 Study to Evaluate Eribulin
Mesylate in Combination with Pembrolizumab in Patients with
Metastatic Triple-negative Breast Cancer" presented at 2016 SABCS.[1]

The study is being conducted under an existing clinical trial
collaboration agreement between the two companies.

About Metastatic Breast Cancer

Metastatic breast cancer is an advanced stage of the disease that
occurs when cancer spreads beyond the breast to other parts of the
body. In 2017, approximately 91,000 women in Europe will die from the
disease.[4] It is estimated that approximately 5 to 10 percent of
women with breast cancer will have metastatic disease at the time of
diagnosis.[5] Of these women, an estimated one in four is expected to
survive five years.[6]

About Halaven® (eribulin)

Eribulin is a microtubule dynamics inhibitor indicated in the
European Union for the treatment of patients with:

- Metastatic breast cancer who have previously received at least two
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.[7]
- Unresectable or metastatic liposarcoma who have received a prior
anthracycline-containing regimen.[7]

Discovered and developed by Eisai, eribulin is a synthetic
analogue of halichondrin B, a natural product that was isolated from
the marine sponge Halichondria okadai.[8]First in the halichondrin
class, eribulin is a microtubule dynamics inhibitor.[8]

Eribulin is believed to work primarily via a tubulin-based
mechanism that causes prolonged and irreversible mitotic blockage,
ultimately leading to apoptotic cell death.[8],[9] Additionally, in
preclinical studies of human breast cancer, eribulin demonstrated
complex effects on the tumour biology of surviving cancer cells,
including increases in vascular perfusion resulting in reduced tumour
hypoxia,[10] and changes in the expression of genes in tumour
specimens associated with a change in phenotype, promoting the
epithelial phenotype, opposing the mesenchymal phenotype.[10]
Eribulin may also decrease the migratory, invasive and metastatic
potential of human breast cancer cells.[11],[12],[13],[14]

About Eisai Co Ltd

Eisai Co Ltd is a leading global research and development-based
pharmaceutical company headquartered in Japan. 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. With over 10,000
employees working across our global network of R&D facilities,
manufacturing sites and marketing subsidiaries, we strive to realise
our hhc philosophy by delivering innovative products in multiple
therapeutic areas with high unmet medical needs, including Oncology
and Neurology.

For more information about Eisai Co., Ltd., please visit
www.eisai.com

References

1. Tolaney S, et al. (2017) Phase 1b/2 study to evaluate eribulin
mesylate in combination with pembrolizumab in patients with
metastatic triple-negative breast cancer. San Antonio Breast Cancer
Symposium 2017; Program Number: PD6-13.

2. Smith II J, et al. (2017) Phase 2 study evaluating the efficacy
and safety of eribulin mesylate administered biweekly for patients
with human epidermal growth factor receptor 2-negative metastatic
breast cancer. San Antonio Breast Cancer Symposium 2017; Poster
Session 6: PD-14-05.

3. Kaul R, et al. (2017) Eribulin differentially disrupts TGF-?
signaling pathway in BT-549 and HCC1937 breast cancer cell lines. San
Antonio Breast Cancer Symposium 2017; Poster Session 5: P5-04-04.

4. Ferlay J, et al. (2016) More deaths from pancreatic cancer than
breast cancer in the EU by 2017. Acta Oncologica. 55,1158-1160.

5. O'Shaughnessy J. (2005). Extending survival with chemotherapy in
metastatic breast cancer. The Oncologist. 10, 20, 20-29.

6. National Cancer Institute. (2011). SEER Stat fact sheets: Breast
cancer. Seer.cancer.gov. Accessed at
http://seer.cancer.gov/statfacts/html/breast.html [Last accessed
December 2017].

7. Eisai. Halaven SPC (Updated August 2017). Accessed at: www.ema.eur
opa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/0 (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002084/WC500105112.pdf)
02084/WC500105112.pdf (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002084/WC500105112.pdf) [Last accessed December 2017].

8. Kuznetsov G, et al. (2004) Induction of morphological and
biochemical apoptosis following prolonged mitotic blockade by
halichondrin B macrocyclic ketone analog E7389. Cancer Research.
64,5760-5766.

9. Towle MJ, et al. (2011) Eribulin induces irreversible mitotic
blockade: implications of cell-based pharmacodynamics for in vivo
efficacy under intermittent dosing conditions. Cancer Research.
71,469-506.

10. Ueda S, et al. (2016) In vivo imaging of eribulin-induced
reoxygenation in advanced breast cancer patients: a comparison to
bevacizumab. British Journal of Cancer. 114,1212-1218.

11. Ozawa Y, et al. (2014) Suppression of metastasis and improvement
of drug distribution by eribulin mesylate. Poster presented at the
26th EORTC-NCI-AACR symposium 2014; Poster 030.

12. Funahashi Y, et al. (2014) Eribulin mesylate reduces the
abnormality of tumor microenvironment by vascular remodelling in
human breast cancer models. Cancer Science. 105,1334-1342.

13. Yoshida T, et al. (2014) Eribulin mesilate suppresses
experimental metastasis of breast cancer cells by reversing phenotype
from epithelial-mesenchymal transition (EMT) to
mesenchymal-epithelial translation (MET) states. British Journal of
Cancer. 110,1497-1505.

14. Agouinik SI, et al. (2014) Eribulin
mesylate exerts specific gene expression changes in pericytes and
shortens pericyte-driven capillary network in vivo. Vascular Cell.
6,3.

Halaven-EU0477

December 2017

ots Originaltext: Eisai
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Bily Kuo
+44 (0) 7739 600 678
Bily_Kuo@eisai.net
Helena Symeou
+44 (0) 7507 309 895
Helena_Symeou@eisai.net Tonic Life Communications: Rizwan Dasu
+44 (0) 208 747 4440
Rizwan.Dasu@toniclc.com

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