Janssen Research & Development, LLC has entered into a clinical trial collaboration agreement with Genentech, a member of the Roche Group, to initiate two studies to determine the safety and tolerability of daratumumab (Darzalex), the first CD38-directed monoclonal antibody (mAb), in combination with atezolizumab, an investigational mAb designed to bind with a protein called programmed cell death-ligand 1 (PD-L1).
These studies will assess the potential of the combination therapy in multiple myeloma and in solid tumour. Atezolizumab is currently in development by Roche. Janssen licensed daratumumab from Genmab A/S and is responsible for development and marketing.
As part of the collaboration, Janssen will sponsor a phase 1b, open-label, multicenter study that will investigate the potential of daratumumab in combination with atezolizumab in patients with solid tumour. Genentech is the sponsor of an ongoing phase 1b, open-label, multicenter study that will be amended to assess atezolizumab in combination with daratumumab, with daratumumab and lenalidomide, and with daratumumab and pomalidomide in patients with relapsed or refractory multiple myeloma. These studies are anticipated to start dosing patients within a year.
"We are excited to see if the immunomodulatory properties of daratumumab may have synergistic treatment effects when used in combination with this promising anti-PDL1 antibody," said Peter F. Lebowitz, M.D., Ph.D., global oncology head, Janssen Research & Development. "This is the first time we're exploring daratumumab in solid tumour, and we look forward to better understanding how combining these two immunotherapies may potentially benefit patients with multiple myeloma and solid tumor, who are urgently in need of new options."
In November 2015, Darzalex was approved by the US Food and Drug Administration for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Darzalex (daratumumab) injection for intravenous use is the first CD38-directed monoclonal antibody (mAb) approved anywhere in the world. CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage. Daratumumab is believed to induce tumor cell death through apoptosis, in which a series of molecular steps in a cell lead to its death as well as immunomodulatory effects and multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin's lymphoma. Darzalex is the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma.
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise Darzalex. Darzalex is commercialised in the US by Janssen Biotech, Inc.
The most frequently reported adverse reactions (incidence =20 per cent) were fatigue, nausea, back pain, pyrexia, cough, and upper respiratory tract infection.
Serious adverse reactions were reported in 51 (33 per cent) patients. The most frequent serious adverse reactions were pneumonia (6 per cent), general physical health deterioration (3 per cent), and pyrexia (3 per cent).