In regard to safety and tolerability, results demonstrated that rociletinib is well-tolerated and lacks the adverse effects typically caused by EGFR TKIs like acne-like rashes.2,3 Rociletinib avoids these adverse effects by targeting only mutated EGFR and not wild-type EGFR.

“[We] designed it to spare wild-type EGFR, which we now know are the causes of the side effects, such as skin rash, pain in the nails, and diarrhea,” Mahaffy said. The most common adverse effects observed with rociletinib include hyperglycemia, diarrhea, nausea, and decreased appetite. Hypoglycemia was the only grade 3 or higher treatment-related adverse event to occur in more than one patient.1

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Clovis Oncology is currently conducting various other studies involving the drug. The TIGER-2 study is investigating the use of rociletinib in patients T790M-positive EGFR-mutated NSCLC who have progressed on their first and only TKI therapy and the TIGER-1 study is comparing the use of rociletinib with erlotinib in patients with newly diagnosed EGFR-mutated NSCLC.

“We have great preclinical evidence for inhibition of the activating mutations of EGFR and we are testing that now in our head-to-head study against Tarceva which began enrolling this month. Data from that study should begin to emerge around this time next year,” Mahaffy said.

The TIGER-3 study is investigating the use of rociletinib versus chemotherapy in patients with T790M-positive and -negative EGFR-mutated NSCLC who have acquired resistance to TKI therapy.

NSCLC accounts for nearly 85% of all lung cancers, and EGFR-activating mutations (L858R and Del19) occur in about 10% to 15% of Caucasian patients with NSCLC and about 30% to 35% of Asian patients with NSCLC.

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The T790M mutation can occur in 60% of patients treated with first- and second-generation EGFR TKIs, thereby reducing the effectiveness of EGFR TKIs in patients with this mutation, however, rociletinib is a promising treatment option for patients with EGFR-mutated NSCLC with or without the T790M mutation.1 

“Our data as presented at this triple meeting demonstrate that we have found a dose at which we deliver really good efficacy with a 67% response rate and about a 90% disease control rate with a well-tolerated profile that delivers that efficacy without any of the rash, paronychia, any of the wild-type-related side effects that have detracted from the benefits of first-line EGFR inhibitors,” Mahaffy said.

Clovis Oncology received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for rociletinib as treatment for patients with T790M-positive EGFR-mutated NSCLC who have progressed on EGFR-targeted therapy and plans to submit a new drug application for rociletinib to the FDA in mid-2015.1


  1. Sussman A, Burkart B. Interim Data from Rociletinib (CO-1686) Phase 1/2 Study Shows Compelling Durable Clinical Activity and Progression-free Survival (PFS) in Patients with EGFR-Mutant Non-small Cell Lung Cancer (NSCLC). Clovis Oncology Press Release. 18 Nov 2014.
  2. Gilotrif (afatinib) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.
  3. Tarceva (erlotinib) [package insert]. San Francisco, CA: Genentech USA, Inc.