Date: 2015-03-17
Type of information: Clinical research agreement
Compound: varlilumab and Tecentriq® (atezolizumab) (MPDL3280A)
Company: Celldex Therapeutics (USA - NJ) Roche (Switzerland)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: immunotherapy product/monoclonal antibody. Anti-PDL1 antibody MPDL3280A is an investigational monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer. In February 2015, MPDL3280A received Breakthrough Therapy from the FDA for the treatment of people whose NSCLC expresses PD-L1 and who progressed during or after standard treatments (e.g., platinum-based chemotherapy and appropriate targeted therapy for EGFR mutation-positive or ALK-positive disease). Roche’s Biologics Licence Application (BLA) for NSCLC was granted Priority Review with an action date of 19 October 2016. Roche has eight Phase III lung studies underway evaluating Tecentriq® alone or in combination with other treatments in patients with early and advanced stages of lung cancer. Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. CD27 can be effectively manipulated with activating antibodies to induce potent anti-tumor responses and may result in fewer toxicities due to its restricted expression and regulation. Varlilumab is a potent anti-CD27 agonist that induces activation and proliferation of human T cells when combined with T cell receptor stimulation. In lymphoid malignancies that express CD27 at high levels, varlilumab may have an additional mechanism of action through a direct anti-tumor effect. Preclinical data suggest the combination of these two mechanisms are synergistic and may enhance anti-tumor immune response compared to either agent alone. In Celldex's Phase 1 study of varlilumab in multiple solid tumors, promising signs of clinical activity in patients with refractory renal cell carcinoma were observed, including a durable partial response (11.0+ months) that has continued to decrease in tumor volume over time and prolonged stable disease (4 patients with a range of 5.3 to 30.7+ months).
Disease: renal cell carcinoma (RCC)
Details: * On March 17, 2015, Celldex Therapeutics announced that it has entered into a clinical trial collaboration with Roche to evaluate the safety, tolerability and preliminary efficacy of varlilumab, Celldex's CD27 targeting investigational antibody, and MPDL3280A (atezolizumab- anti-PDL1), Roche's investigational cancer immunotherapy in a Phase 1/2 study in renal cell carcinoma. Under the terms of this agreement, Roche will provide study drug and Celldex will be responsible for conducting and funding the study, which is expected to begin in 2015.
Financial terms:
Latest news: * On August 28, 2015, a Phase 1/2 study sponsored by Celldex Therapeutics was published on the NIH website ClinicalTrials.gov for varlilumab and atezolizumab and is currently recruiting participants.
