On December 8, 2016 Leading oncology biopharmaceutical company BerGenBio AS, reported important new preclinical study data on its first-in-class AXL inhibitor, BGB324 in another major disease indication (Press release, BerGenBio, DEC 8, 2016, View Source [SID1234517008]). The study in breast cancer showed that AXL, a key factor in tumor resistance to the emerging class of new immune checkpoint inhibitors is effectively targeted through combination therapy with BGB324. The study data was presented in a poster today at the San Antonio Breast Cancer Symposium 2016.

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BGB324 is a highly selective small molecule inhibitor of the AXL receptor tyrosine kinase that is associated with poor overall survival in breast cancer. The new study "BGB324, a selective small molecule inhibitor of AXL tyrosine kinase, enhances immune checkpoint inhibitor efficacy in mammary adenocarcinoma" presented today in the Immunology and Preclinical Immunotherapy poster session, described a unique role for AXL in suppressing the anti-tumor immune response in breast cancer. AXL-targeting with BGB324 enhanced the effect of immune checkpoint blockade in aggressive mammary adenocarcinomas that display limited immunogenicity. The results showed that AXL-associated EMT and expression of immune suppressive cytokines increased in 4T1 tumors in response to immune therapy and correlated with a lack of response. The combination of BGB324 + anti-CTLA-4/anti-PD-1 resulted in durable primary tumor clearance and sustained tumor immunity in animals that rejected 4T1 tumor cell re-challenge. Importantly, the extensive metastasis to the lung, liver and spleen characteristic of this breast cancer model were concomitantly abrogated in the animals responding to the combination treatment. BGB324 enhanced tumor infiltration of effector cytotoxic T lymphocytes and NK cells while decreasing immune suppressive cell types. Notably, BGB324 showed direct effects on human M2 macrophages, reducing secretion of immune suppressive cytokines. Hence, selective inhibition of AXL signaling with BGB324 uniquely targets both tumor intrinsic and microenvironmental immune suppression mechanisms and increases checkpoint inhibitor efficacy.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented:
"We believe this strong new preclinical data again clearly demonstrates the rationale for combining BGB324 with immune checkpoint inhibitors to treat a wide range of aggressive cancers. AXL expression is increased in tumors in response to checkpoint inhibitor treatment and is an important resistance mechanism. Treatment with BGB324 counters this and promotes the anti-tumor immune response. This supports our intention to combine the clinical-stage selective Axl inhibitor BGB324 with immune checkpoint inhibitors to improve treatment of human breast cancer."

About BGB324
BGB324 is a first-in-class, highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition (EMT), which is a key driver in immune evasion, drug-resistance and metastasis. Phase Ib clinical trials are underway as single agent and in combination with standard of care drugs cytarabine in acute myeloid leukaemia (AML) and erlotinib in non-small cell lung cancer (NSCLC).

On December 8, 2016 Eli Lilly and Company (NYSE: LLY) reported that the neoMONARCH study of abemaciclib, a cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor, met its primary endpoint of reducing expression of Ki67, a biomarker of cell proliferation, after two weeks of treatment (Press release, Eli Lilly, DEC 8, 2016, View Source [SID1234516998]). Final data from the Phase 2 trial presented during the official press program at the 2016 San Antonio Breast Cancer Symposium (SABCS) evaluated abemaciclib, both alone or in combination with the non-steroidal aromatase-inhibitor anastrozole, in postmenopausal women with previously untreated early stage hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

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"Lilly is committed to the scientific discovery and development of new therapies that change current standards of cancer care," said Sue Mahony, Ph.D., senior vice president and president, Lilly Oncology. "The neoMONARCH data are encouraging and continue to inform our understanding of how abemaciclib could be used as both a single-agent therapy or in combination with aromatase inhibitors, such as anastrozole, in the early-stage setting."

The Phase 2 neoMONARCH trial was a randomized, multi-center, open-label study that enrolled 225 patients who had at least one measurable tumor ≥1 cm, adequate organ function, and an ECOG performance status of ≤1. Patients were randomized to one of three trial arms: 1) twice-daily abemaciclib monotherapy (150mg) for two weeks; 2) twice-daily abemaciclib (150mg) along with once-daily anastrozole (1mg) for two weeks; or 3) once-daily anastrozole monotherapy (1mg) for two weeks. All patients received an initial biopsy prior to randomization to assess baseline Ki67 expression. After the initial two-week treatment period, patients underwent a second tumor biopsy and Ki67 was assessed again.

The primary objective of the study was to assess Ki67 percentage change in the breast tumor after two weeks of therapy from the baseline measurement. The results showed that abemaciclib monotherapy and abemaciclib in combination with anastrozole significantly reduced Ki67 more than anastrozole alone. Following the initial two weeks of randomized treatment, all patients then went on to receive twice-daily abemaciclib (150mg) plus anastrozole (1mg) for a further 14 to 22 weeks.

The study protocol also included the prophylactic use of loperamide (2mg) administered twice-daily, in combination with abemaciclib for the first 28 days. No new safety signals were observed for abemaciclib when administered in combination with anastrozole.

Breast cancer is the most common cancer among American women, besides skin cancers, and is the second leading cause of cancer death among women.1 An estimated 61,000 cases of early-stage breast cancer will be diagnosed in the U.S. this year and one in eight women, or 12 percent, of women in the U.S. will develop invasive breast cancer during their lifetime.1

About Abemaciclib
Abemaciclib (LY2835219) is an investigational, oral cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting cyclin-dependent kinases, CDK 4 and CDK 6. In many cancers, uncontrolled cell growth arises from a loss of cell cycle regulation due to increased signaling from CDK 4 and CDK 6. Abemaciclib inhibits both CDK 4 and CDK 6, and was shown in cell-free enzymatic assays to be most active against Cyclin D 1 and CDK 4.

In 2015, the U.S. Food and Drug Administration granted abemaciclib Breakthrough Therapy Designation based on data from the breast cancer cohort expansion of the company’s Phase 1 trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. In addition to its current MONARCH clinical trials evaluating abemaciclib in breast cancer, a Phase 3 trial of abemaciclib in lung cancer is also underway.

For more information on additional abemaciclib trials, a complete listing can be found on ClinicalTrials.gov (in the search box on the home page, type in "abemaciclib").