Merck & Co, Eli Lilly Form Immuno-Oncology Clinical Trial Pact
Merck & Co. and Eli Lilly and Company have formed an oncology clinical trial collaboration to evaluate the safety, tolerability and efficacy of Keytruda (pembrolizumab), Merck's anti-PD-1 therapy, in combination with Lilly compounds in multiple clinical trials.
Merck will conduct a Phase II study examining the combination of pembrolizumab with pemetrexed in first-line non-squamous, non-small cell lung cancer (NSCLC). This study is currently enrolling.
Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands. It releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. It is approved in the United States for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is 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 this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Lilly’s Alimta (pemetrexed) is an anticancer drug approved for several indications. In 2004, Alimta received consecutive approvals: it was the first agent to be approved in combination with cisplatin as a treatment for patients with malignant pleural mesothelioma, whose disease is unresectable or who are otherwise not candidates for curative surgery, and then as a single agent for the second-line treatment of patients with locally advanced or metastatic NSCLC after prior chemotherapy treatment. In 2008, Alimta, in combination with cisplatin, was approved as a first-line treatment for locally advanced or metastatic NSCLC for patients with nonsquamous histology. At the time of the first-line approval, the US Food and Drug Administration (FDA) also approved a change to the second-line indication. It is now indicated as a single agent for the treatment of patients with locally advanced or metastatic, nonsquamous NSCLC after prior chemotherapy. In 2009, it was approved as a maintenance therapy for locally advanced or metastatic NSCLC, specifically for patients with a nonsquamous histology whose disease has not progressed after four cycles of platinum-based first-line chemotherapy, and it was approved in 2012 by the FDA as a continuation maintenance therapy for locally-advanced or metastatic NSCLC, following first-line therapy with Alimta plus cisplatin in patients with a nonsquamous histology. The drug is not indicated for treatment of patients with squamous cell NSCLC. Myelosuppression is usually the dose-limiting toxicity with ALIMTA therapy.
Lilly also will conduct a multiple-arm Phase I/II study examining the combination of ramucirumab with pembrolizumab in multiple tumors. This study is anticipated to begin in 2015. Ramucirumab is the active ingredient in Lilly’s Cyramza. It is approved as a single agent, or in combination with paclitaxel (a type of chemotherapy) for the treatment of people with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Lilly will conduct a Phase 1/II study examining the combination of necitumumab with pembrolizumab in NSCLC. This study is anticipated to begin in 2015. Necitumumab is Lilly’s investigational recombinant human IgG1 monoclonal antibody that is designed to block the ligand binding site of the human epidermal growth factor receptor 1 (EGFR). Activation of EGFR has been correlated with malignant progression, induction of angiogenesis and inhibition of apoptosis or cell death.
The agreement is between Lilly and Merck, through a subsidiary. Additional details of the collaboration were not disclosed.