Eisai’s Cancer Strategy Bears Early IO Combo Fruit
Executive Summary
Interim data from a Phase Ib/II of a combination of Eisai’s halichondrin Halaven with Merck & Co’s immuno-oncology product Keytruda suggest it could represent a novel treatment regimen in patients with metastatic triple negative breast cancer, in an early vindication for the Japanese company’s strategy of expanding its oncology franchise.
Early data from an open-label, single-arm, multicentre Phase Ib/II study investigating the combination of Eisai Inc.’s Halaven (eribulin) with Merck & Co. Inc.’s Keytruda (pembrolizumab) in 106 patients with metastatic breast cancer who had previously treated with up to two lines of chemotherapy showed an overall response rate of 33.3% in the 39 patients evaluable so far. One patient had a complete response and twelve patients a partial response. The overall response rate was also similar between both PD-L1 positive and negative cohorts.
Eribulin is the first in the halichondrin class of microtubule dynamics inhibitors and is approved in the EU and US for locally advanced or metastatic breast cancer which has progressed after at least one chemotherapeutic regimen for advanced disease, as well as for use in liposarcoma and soft tissue sarcoma. Keytruda is available for NSCLC and melanoma and is in Phase development for use as a single agent in metastatic triple negative breast cancer.
Study researcher Dr Sara Tolaney of the Dana-Farber Cancer Institute in Boston explained the rationale behind the combination: in preclinical and translational studies, eribulin induced tumor vascular remodeling, reduction of hypoxia and promotion of the less aggressive epithelial phenotype in advanced breast cancer tumor tissue, she said. “We hypothesised that these effects of eribulin on tumour biology and microenvironment may increase the drug delivery of immune checkpoint inhibitor, pembrolizumab, in metastatic triple negative breast cancer and further enhance the possibility that pembrolizumab would enable the immune system's T cells to detect and attack tumor cells."
Adverse events with the combination were comparable to those observed with either treatment as monotherapy, the researchers found. The most frequent adverse events of grade 3 or higher included neutropenia (31%) and fatigue (8%). Serious adverse events occurred in 36% of patients and adverse events leading to dose adjustment were observed in 56%. The data were presented at the San Antonio Breast Cancer Symposium in Texas this week.
Further results from the study are due in August 2017.
Oncology is a key area for Eisai, alongside its neurology portfolio. In July, the company stated its short-term focus in the area was on expanding the approved indications for its other major cancer therapy Lenvima (lenvatinib), firstly into liver cancer and then onto first-line renal cell carcinoma, where it is being tested in a three-arm study that includes its combination with Keytruda. Eisai is also testing Lenvima with Keytruda in other solid tumors.
But Halaven has its part to play in Eisai’s oncology ambitions, including with the Keytruda triple negative breast cancer combo. The Halaven and Lenvima combination studies with Keytruda follow a deal with Merck & Co signed in 2015. (Also see "Merck & Co And Eisai Link Up For Combo Cancer Studies" - Scrip, 9 Mar, 2015.)
Also a new Phase Ib/II study of Halaven in combination with PEGylated recombinant human hyaluronidase (PEGPH20) is enrolling about 114 patients with human epidermal growth factor receptor 2-negative (HER2-) high hyaluronan metastatic breast cancer, who were previously treated with up to two lines of systemic anticancer therapy in the metastatic setting. (Also see "Eisai hopes for Halaven bump with combo" - Scrip, 31 Jul, 2015.)