Date: 2018-05-26
Type of
information: Halting of the trial
phase: 1b
Announcement: discontinuation of development
Company: Janssen Biotech, a J&J company (USA - NJ)
Product: atezolizumab (MPDL3280A) and daratumumab
Action
mechanism:
- immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. 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.
- Daratumumab is a human CD38 monoclonal antibody with broad-spectrum killing activity. Daratumumab is in clinical development for multiple myeloma. It targets the CD38 molecule which is highly expressed on the surface of multiple myeloma cells and may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the FDA 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 (IMiD) or who are double refractory to a PI and an IMiD. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.
Disease: solid tumors
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
- The LUC2001 study is a randomized, multicenter, Phase Ib/II study. The study includes 98 patients with previously treated advanced or metastatic NSCLC. Patients will be randomized to receive daratumumab at 16 milligrams per kilogram (mg/kg) weekly for 3 cycles and on day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1,200 mg on day 2 of Cycle 1 and on day 1 of every 21-day cycle thereafter. Patients will continue to receive treatment until disease progression or unacceptable toxicity. Patients in the atezolizumab monotherapy arm with confirmed disease progression will be eligible to crossover to the daratumumab plus atezolizumab arm, if they meet the crossover eligibility criteria. The primary endpoint of the study is percentage of patients with ORR, defined as percentage of patients with PR or CR as defined by Response Evaluation Criteria in Solid Tumors (RECIST). (NCT03023423)
Latest
news:
- • On May 26, 2018, Genmab announced that following a planned review, the DMC has recommended that the Phase Ib/II study (CALLISTO/LUC2001) of daratumumab in combination with atezolizumab versus atezolizumab monotherapy in patients with previously treated advanced or metastatic non-small cell lung cancer should be terminated. The DMC determined that there was no observed benefit within the combination treatment arm, daratumumab plus atezolizumab, over atezolizumab monotherapy, and recommended termination of the study. In addition to the lack of benefit, the DMC noted a numerical increase in mortality-related events in the combination arm.
- • On March 21, 2016, Genmab announced that daratumumab will be investigated in early stage clinical studies in combination with atezolizumab (anti-PD-L1 antibody), in a solid tumor. The study will be conducted under a clinical trial collaboration agreement between Genmab's licensing partner for daratumumab, Janssen Biotech and Genentech. 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 tumor. The study us anticipated to start dosing patients within a year.
Is
general: Yes
