Date: 2016-01-27
Type of information: Initiation of the trial
phase: 1b-2
Announcement: initiation of the trial
Company: Clovis Oncology (USA - CO) Genentech, a member of Roche Group (USA - CA - Switzerland)
Product: rociletinib (CO-1686) and atezolizumab (MPDL3280A)
Action
mechanism: immunotherapy product/monoclonal antibody/immune checkoint inhibitor. Anti-PDL1 antibody atezolizumab (MPDL3280A) is a 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. kinase inhibitor/tyrosine kinase inhibitor. Rociletinib is an oral, potent, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) under investigation for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Rociletinib targets the activating mutations of EGFR (L858R and Del19), while also inhibiting the dominant acquired resistance mutation, T790M, which develops in approximately 60 percent of patients treated with first- and second-generation EGFR inhibitors, while sparing wild-type, or “normal” EGFR at anticipated therapeutic doses. Accordingly, it has the potential to treat NSCLC patients with EGFR mutations both as a first-line or second-line treatment with a potentially reduced toxicity profile. Rociletinib was granted Breakthrough Therapy designation by the FDA in May 2014. Clovis announced on August 3 that it submitted its New Drug Application (NDA) regulatory filing to the FDA and submitted its Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) through the centralized procedure for rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy.
Disease: advanced EGFR-mutant non-small cell lung cancer (NSCLC)
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This clinical research study is being carried out in two parts, Phase 1 and Phase 2. The primary purpose of the Phase 1 portion of the study is to observe the safety of the combination of rociletinib and MPDL3280A in EGFR-mutant NSCLC patients. The primary purpose of the Phase 2 portion of the study is to evaluate the safety and anti-tumor effects of the combination of rociletinib and MPDL3280A, at the best doses for the combination determined in Phase 1, in patients with EGFR-mutant NSCLC. (NCT02630186 )
Latest
news: * On January 27, 2016, Clovis Oncology announced that it initiated a clinical trial to evaluate a novel combination therapy of Genentech’s cancer immunotherapy atezolizumab (MPDL3280A; anti-PD-L1) and rociletinib for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). The Phase 1b/2 trial of rociletinib in combination with atezolizumab, which is sponsored by Clovis, is designed to assess the safety and activity of the combination in patients with activating EGFR mutation-positive (EGFRm) advanced or metastatic NSCLC. The Phase 1b portion of the trial will evaluate the safety, tolerability and pharmacokinetics of the combination in this population. The Phase 2 portion of the trial will evaluate the activity of the combination in two subgroups of patients with EGFR-mutant advanced or metastatic NSCLC: those who have not previously received an EGFR tyrosine kinase inhibitor (TKI) or chemotherapy, and those who have progressed on a prior EGFR TKI. T790M-negative and T790M-positive patients will be enrolled in the Phase 1b portion of the trial and in the Phase 2 portion of the trial in the subgroup of patients who have progressed on a prior EGFR TKI. While patients’ tumors are not required to express PD-L1 to enroll in the study, PD-L1 expression will be assessed in archival and/or fresh tissue as part of the study. The University of California in Los Angeles (UCLA) is the first site to initiate the trial, with the first patient expected to be enrolled within a few weeks. Additional patients will begin to enroll in sites throughout the U.S. and E.U., and initial safety and tolerability results from the study are expected at the World Conference on Lung Cancer in the fall of 2016.
