Encouraging Updated Results from Phase 1b/2 Study Evaluating the Combination of Eribulin Mesylate and Pembrolizumab in P

HATFIELD, England, December 8, 2017 /PRNewswire/ --

Eisai today announced updated results of ENHANCE 1, a Phase 1b/2 trial investigating eribulin mesylate (Halaven(R)), 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(R)), 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-beta 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(R) 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/NCT0... ] 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(R) (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]

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