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Clinical Trials

Date: 2017-06-03

Type of information: Results

phase: 3

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: Eli Lilly (USA - IN)

Product: abemaciclib (LY2835219)

Action mechanism:

  • cell cycle inhibitor/cyclin dependant kinase inhibitor. Abemaciclib (LY2835219) is a cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting CDK 4 and 6. Although abemaciclib inhibits both CDK 4 and CDK 6, the results from the cell-free enzymatic assays have shown that it was most active against Cyclin D 1 and CDK 4.

Disease: hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer

Therapeutic area: Cancer - Oncology

Country: Australia, Belgium, Canada, Denmark, Finland, France, Germany, Greece, Italy, Japan, Republic of Korea, Mexico, Poland, Puerto Rico, Romania, Russian Federation, Spain, Switzerland, Taiwan, USA

Trial details:

  • The main purpose of this phase 3 study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either abemaciclib+fulvestrant or fulvestrant alone. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio. The study will last about 9 months for each participant. The intent-to-treat population of 669 patients was randomized to receive abemaciclib or placebo orally twice a day on a continuous dosing schedule, given in combination with fulvestrant at its approved dose and schedule, until disease progression. Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease. Patients who had received chemotherapy in the metastatic setting were not eligible for the study.  The study was conducted across 142 sites worldwide.(NCT02107703)

Latest news:

  • • On June 3, 2017,  Eli Lilly announced that results from the Phase 3 MONARCH 2 study showed that abemaciclib, a cyclin-dependent kinase (CDK)4 & 6 inhibitor, in combination with fulvestrant, significantly improved progression-free survival (PFS) compared to treatment with fulvestrant alone in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy (median PFS, 16.4 vs. 9.3 months, respectively, HR: 0.553; 95% CI: 0.449, 0.681, P < .0000001). The data were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #1000) and simultaneously published online in the Journal of Clinical Oncology.
  • Patients with measureable disease treated with abemaciclib plus fulvestrant achieved an objective response rate (ORR) of 48.1 percent (3.5% complete response [CR]), compared to 21.3 percent (0% CR) in patients treated with fulvestrant alone. Additionally, abemaciclib plus fulvestrant caused a greater degree of tumor shrinkage than fulvestrant alone.
  • The most frequent adverse events (AEs) of any grade in the abemaciclib plus fulvestrant arm were diarrhea, neutropenia, nausea, and fatigue. Of these, the reported Grade 3 AEs (abemaciclib vs. placebo arm) were diarrhea (13.4% vs. 0.4%), neutropenia (23.6% vs. 1.3%), nausea (2.7% vs. 0.9%), and fatigue (2.7% vs. 0.4%). No patients in either arm experienced Grade 4 diarrhea, nausea or fatigue, and Grade 4 neutropenia was observed in 2.9 percent versus 0.4 percent of patients in the abemaciclib versus placebo arms, respectively.
  • Severity and frequency of diarrhea generally decreased following one to two cycles, and was managed with loperamide or dose reduction. The majority (70.1%) of patients in the abemaciclib arm with an AE of diarrhea did not require treatment modification (dose interruption, reduction, or discontinuation), and 2.9 percent of patients discontinued the study drug due to diarrhea.
  • • On March 20, 2017, Eli Lilly  announced that its MONARCH 2 trial of abemaciclib met the primary endpoint of progression-free survival (PFS). The Phase 3 study evaluated abemaciclib in combination with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy.
  • The results demonstrated the addition of abemaciclib to fulvestrant resulted in a statistically significant improvement in PFS, when compared to the control arm of placebo plus fulvestrant. Detailed efficacy and safety results will be presented at an upcoming medical meeting.
  • The most common adverse events observed were diarrhea, neutropenia, nausea and fatigue, and were consistent with the previous studies of abemaciclib.
  • Lilly intends to submit a new drug application (NDA) for single-agent abemaciclib in the second quarter of 2017, based on the MONARCH 1 study, for the treatment of refractory metastatic breast cancer patients whose disease had progressed following multiple prior treatments, including endocrine therapy and one to two chemotherapy regimens in the metastatic setting. Lilly plans to submit an additional application for MONARCH 2 in the third quarter of this year.
  • • On August 10, 2016, Eli Lilly announced that following a pre-planned interim analysis for MONARCH 2, an independent Data Monitoring Committee (DMC) provided the recommendation to continue the study without modification as the interim efficacy criteria were not met. The MONARCH 2, Phase 3 trial compares abemaciclib plus fulvestrant* versus placebo with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer.
  • The trial will continue into the first half of 2017 and will include a final analysis of PFS, overall survival and safety data. Lilly will await further data and continue to work with the FDA to inform its submission plan for single-agent abemaciclib, based on the MONARCH 1 study. This Phase 2 study evaluated the single-agent activity and safety of abemaciclib in patients with refractory metastatic breast cancer, whose disease had progressed following multiple prior treatments, including chemotherapy.

Is general: Yes