Pembrolizumab, Abemaciclib Cancer Immunotherapy Combo Study Planned

In addition to the current scope of Merck & Co and Eli Lilly‘s immuno-oncology alliance, the companies will evaluate a combination of Keytruda, Merck’s PD-1 inhibitor with Lilly’s cyclin-dependent kinase 4 and 6 inhibitor abemaciclib.

The Phase I study across multiple tumor types will be based on the Phase I trial results. The collaboration has the potential to progress to Phase II trials in patients who have been diagnosed with either metastatic breast cancer or non-small cell lung cancer (NSCLC).

Per the agreement, Lilly is sponsoring the Phase I study, expected to start enrolling patients early next year, and any subsequent Phase II studies. Financial details of the collaboration were not disclosed.

Keytruda (pembrolizumab) is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.

Lilly’s abemaciclib (LY2835219), is a cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting CDK4 and CDK6.

Said Eric Rubin, M.D., vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories:

“We look forward to continuing our collaboration with Lilly on this combination study with KEYTRUDA and abemaciclib. Strategic collaborations such as this one reinforce the commitment we have to bringing new combination treatments to the forefront for people with cancer.”

Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology, addeed:

“With our active Phase III program underway for abemaciclib in both metastatic breast cancer and non-small cell lung cancer, we are committed to uncovering every opportunity to help these patients – and this includes exploring abemaciclib in combination with immunotherapy.

We’re encouraged by our productive immuno-oncology collaborations with Merck, through its affiliates, and coming together for another clinical trial is a natural evolution of our scientific collaboration.”

Abemaciclib

Abemaciclib is in Phase III development with two trials in HR+ breast cancer patients, as well as a Phase III trial in lung cancer.

Cyclin-dependent kinases play a key role in regulating cell cycle progression. In many cancers, uncontrolled cell growth arises from a loss of control in regulating the cell cycle due to increased signaling from CDK4 and CDK6. Lilly’s abemaciclib (LY2835219) is a cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting CDK4 and CDK6, and in cell-free enzymatic assays has been shown to be most active against Cyclin D1/CDK4.

Results from preclinical and early-stage clinical studies support the further evaluation of abemaciclib for the treatment of human cancers, including breast cancer and lung cancer – in which aberrant CDK4 and CDK6 pathways enhance cancer cell growth.

Pembrolizumab

Keytruda (pembrolizumab) is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Keytruda is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy.

Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda.

Keytruda is also indicated at the same dosing for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. These indications are approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established.

Continued approval for these indications may be contingent upon verification and description of clinical benefit in the confirmatory trials.