On January 27, 2016 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that it initiated a clinical trial to evaluate a novel combination therapy of Genentech’s investigational cancer immunotherapy atezolizumab (MPDL3280A; anti-PD-L1) and rociletinib for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) (Press release, Clovis Oncology, JAN 27, 2016, View Source [SID:1234508872]). Rociletinib is the Company’s novel, oral targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M.

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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.

"We are pleased to be enrolling patients at UCLA to explore this combination therapy for advanced EGFR-mutant non-small cell lung cancer patients, for whom additional treatment options are needed," said Dr. Jonathan Goldman, Director, Clinical Trials in Thoracic Oncology, Associate Director of Drug Development at UCLA and Principal Investigator. "We obviously hope to see meaningful synergy and patient benefit by combining the effects of immuno-oncology with a targeted therapy."

"I am excited to explore this combination with rociletinib to determine if we can bring the promise of long-term benefit of PD-L1 inhibitors seen in other lung cancer sub-types to those patients with mutant EGFR driven tumors", said Professor Jean-Charles Soria, Professor of Medicine and Medical Oncology at Paris University XI, Cancer Specialist at Gustav Roussy and lead Principal Investigator.

Currently, rociletinib is under review by the U.S. Food and Drug Administration and European Medicines Agency.

"Rociletinib’s activity and safety profile observed in our monotherapy trials suggest that rociletinib may be an attractive agent for combination use," said Patrick Mahaffy, President and CEO of Clovis Oncology. "We are committed to exploring the potential of rociletinib both as monotherapy and in combination to help patients with lung cancer who may benefit."

About Rociletinib

Rociletinib is the company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of EGFR in development for the treatment of NSCLC in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. Data from both the pivotal, single-arm TIGER-X and TIGER-2 clinical trials served as the basis for the U.S. and EU regulatory submissions for the treatment of advanced mutant EGFR T790M-positive lung cancer. Rociletinib was granted Breakthrough Therapy designation by the FDA in May 2014.

About Lung Cancer and EGFR Mutations

Lung cancer is the most common cancer worldwide with 1.35 million new cases annually, with NSCLC accounting for almost 85 percent of all lung cancers. NSCLC progresses rapidly with a five-year survival rate in advanced NSCLC patients of less than five percent. EGFR activating mutations occur in approximately 10 to 15 percent of NSCLC cases in Caucasian patients and approximately 30 to 35 percent in East Asian patients. These patients often experience significant tumor response to erlotinib, afatinib and gefitinib, which are first- and second-generation EGFR inhibitors. However, most patients ultimately progress on these therapies, with approximately 60 percent of patients developing acquired resistance from a second, "gatekeeper" mutation, T790M.