Study to evaluate the combination of rociletinib (CO-1686) with Genentech's atezolizumab (MPDL3280A) for patients with advanced EGFR-mutant non-small cell lung cancer
The Phase 1b/2 trial of rociletinib in combination with atezolizumab is planned to begin enrolling patients before the end of 2015. The trial, 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 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.
"We are delighted to evaluate atezolizumab with rociletinib to explore whether the combination can add to the clinical benefit in patients with mutant EGFR non-small cell lung cancer," said
Rociletinib was granted Breakthrough Therapy designation by the
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.
Clovis has several studies in EGFR-mutant NSCLC underway:
- TIGER-X is a Phase 1/2 study designed to evaluate the safety and efficacy of three different doses of rociletinib in a very advanced patient population.
- TIGER-1 is a randomized Phase 2/3 registration study versus erlotinib in newly-diagnosed patients.
- TIGER-2 is a global registration study underway in both T790M-positive and T790M-negative patients directly after progression on their first and only TKI therapy.
- TIGER-3 is a randomized, comparative study versus chemotherapy in both T790M-positive and T790M-negative patients with acquired TKI resistance.
A Phase 1 study of rociletinib in
Japanhas completed enrollment and a Phase 2 study in Japanese patients, agreed upon with Japanese regulatory authorities, is expected to initiate in the second half of 2015.
- Multiple combination studies are planned to initiate in the second half of 2015, including inhibitors PD-1 and MEK.
- For more information, please visit www.tigertrials.com.
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. Currently, no targeted therapies are approved for treatment of this mutation.
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