Merck, known as MSD outside the US and Canada, and Eli Lilly and Company announced 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.
Under the terms of the agreement, Merck will conduct a phase 2 study examining the combination of pembrolizumab with pemetrexed in first-line non-squamous, non-small cell lung cancer (NSCLC). This study is currently enrolling.
Lilly will conduct a multiple-arm phase 1/2 study examining the combination of ramucirumab with pembrolizumab in multiple tumors. This study is anticipated to begin in 2015.
Lilly will conduct a phase 1/2 study examining the combination of necitumumab with pembrolizumab in NSCLC. This study is anticipated to begin in 2015.
The agreement is between Lilly and Merck, through a subsidiary. Additional details of the collaboration were not disclosed.
"Cancer is not one disease but rather more than 200 diseases, all of which have different causes and treatments," said Richard Gaynor, M.D., senior vice president, product development and medical affairs, Lilly Oncology. "Therefore research into combinations of immune-based therapies with other agents that could address these different tumor types is important. This collaboration between Lilly and Merck represents each company's strong commitment to patients fighting these devastating diseases."
"Our understanding of the immune system's role and its impact in the treatment of cancer continues to grow," said Eric Rubin, M.D., vice president, global clinical development, oncology, Merck Research Laboratories. "Collaborations such as this one are important in advancing the investigation of novel immuno-oncology combinations in different cancers, and to achieving our shared goal of bringing meaningful benefits to patients facing cancer."
Keytruda (pembrolizumab) 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, Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
Keytruda is indicated in the United States at a dose of 2 mg/kg every three weeks 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.
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 FDA also approved a change to the second-line indication. Alimta is now indicated as a single agent for the treatment of patients with locally advanced or metastatic, nonsquamous NSCLC after prior chemotherapy.
In 2009, Alimta 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.
In 2012, Alimta was approved 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.
Alimta is not indicated for treatment of patients with squamous cell NSCLC. Myelosuppression is usually the dose-limiting toxicity with Alimta therapy.
Cyramza as a single agent, or in combination with paclitaxel (a type of chemotherapy), is approved 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.
Cyramza is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2, by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. Cyramza inhibited angiogenesis in an in vivo animal model.
Necitumumab is an 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.