Boehringer Ingelheim and Eli Lilly will collaborate on a Phase 1b clinical trial to assess the safety and tolerability of Boehringer Ingelheim’s BI 836845 in combination with Lilly’s abemaciclib (LY2835219) to treat patients with HR+/HER2- metastatic breast cancer (mBC).
The companies believe these two agents used in combination could offer more complete pathway interference and potentially extend cell cycle arrest. For patients with HR+/HER2- mBC, this could reverse resistance to hormone therapy.
The new collaboration, which is based on Phase 1b data, has the potential to expand to Phase 2 clinical trials in patients with HR+/HER2- mBC as well as other solid tumors. Patient enrollment is planned to commence later this year. Boehringer Ingelheim will act as sponsor of the trial program.
Richard Gaynor, MD, senior vice president of product development and medical affairs for Lilly Oncology, said in a press release the company was pleased to partner with Boehringer Ingelheim for the combination project, and that Lilly has an active Phase 3 trial underway for abemaciclib.
“For patients living with metastatic breast cancer, the limited treatment options available make this an important area of focus for our efforts to advance the most innovative treatments,” he said.
Dr. Mehdi Shahidi, medical head of Solid Tumor Oncology at Boehringer Ingelheim, said Boehringer is excited about the collaboration “to investigate a novel combination of two compounds that have individually shown promising results in metastatic breast cancer and have a complementary mode of action.”
“We hope that this study will lay foundations for making much-needed new therapies available to patients with metastatic breast cancer,” he said.
BI 836845 is a humanized IgG1 insulin-like growth factor (IGF) monoclonal antibody targeting the IGF ligands 1 (IGF-1) and 2 (IGF-2). Upon administration, it inhibits the binding of IGF-1 and -2 ligands to their receptor, IGF-1R, blocking the insulin growth factor (IGF) signaling pathway, which is upregulated in breast cancer and plays a key role in cancer cell proliferation and chemoresistance. Additionally, BI 836845 prevents the binding of IGF-2 to insulin receptor variant A (IR-A), preventing its activation.
Results of a Phase 1b/2 trial demonstrated promising preliminary efficacy of BI 836845 as well as good clinical safety when used in combination with everolimus and exemestane in patients with HR+ mBC.
Abemaciclib is an orally available cyclin-dependent kinase (CDK) inhibitor that targets the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathway, thereby inhibiting retinoblastoma (Rb) protein phosphorylation and halting cancer cell proliferation.
Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, arresting the cell cycle in the G1 phase, suppressing DNA synthesis, and inhibiting cancer cell growth. Overexpression of the serine/threonine kinases CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.