Rociletinib success in TIGER-X study for NSCLC- Clovis Oncology

Clovis Oncology announced updated findings from its Phase II clinical study of rociletinib (CO-1686), the Company�s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer (NSCLC) in patients with initial activating EGFR mutations, as well as the dominant resistance mutation T790M. These data from the TIGER-X trial are being presented in an oral presentation (Abstract #8001) at the 2015 American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Data presented are from the TIGER-X trial of 456 mutant EGFR NSCLC patients treated with rociletinib tablets at each of the efficacious dose groups studied (all doses BID): 500mg (n=119), 625mg (n=236), 750mg (n=95) and 1000mg (n=6) doses. Efficacy data from 243 centrally confirmed tissue T790M-positive patients, 35 centrally confirmed tissue T790M-negative patients and 147 plasma T790M-positive patients were also presented. Patients enrolled in trial were heavily pretreated prior to receiving rociletinib. Eighty-two percent of patients across all doses had immediately progressed on TKI therapy prior to rociletinib treatment. Seventy-two percent of patients had an ECOG performance score of one or higher. Additionally, patients with stable CNS metastases were allowed in the trial. Forty-one percent of study participants had a history of CNS metastases. A total of 243 centrally confirmed tissue T790M-positive patients were evaluable in the four dose subgroups (all doses BID): 500mg (n=48), 625mg (n=114), 750mg (n=77) and 1000mg (n=4). At the recommended dose of 500mg, a 60 percent ORR (overall response rate) and a 90 percent DCR was observed, and across all doses, a 53 percent ORR and an 85 percent DCR was observed. At the time of analysis, a median PFS ( progression free survival) of 10.3 months was observed in 163 heavily pretreated centrally confirmed tissue T790M-positive patients without a history of CNS metastases, while a median PFS of 8 months was observed in 270 heavily pretreated centrally confirmed tissue T790M-positive patients, of whom 40 percent had a history of CNS metastases. Clinical benefit was durable with some patients on drug for over two years without disease progression. These data continue to mature.

A total of 147 evaluable plasma T790M-positive patients were treated with rociletinib; in those treated with 500mg, a 57 percent ORR and an 80 percent DCR has been observed to date, and at all doses, a 53 percent ORR and an 82 percent DCR has been observed, which is highly consistent with the comparable tissue outcomes data. These data suggest that T790M plasma testing may be an alternative to tissue testing. Rociletinib activity was also observed in 35 evaluable T790M-negative patients treated at all doses. A 37 percent ORR has been observed, in a range of 32 to 39 percent across doses studied. Eighty-six percent of these patients were treated with rociletinib directly after TKI therapy, so a TKI re-treatment effect cannot be the driver of this activity. The data presented at ASCO continue to demonstrate rociletinib is well tolerated. In the 500mg dose group, the most common treatment-related AEs reported in greater than 10 percent of all patients included hyperglycemia, diarrhea and nausea.

Data from TIGER-X trial, combined with data from the TIGER-2 study, will form the U.S. New Drug Application (NDA) and E.U. Marketing Authorization Application (MAA) submission packages in July 2015.

Comment: The company determined that, based on the trial results, the ideal dose of rociletinib is the 500mg dose.

Comment:Clovis delivered a progression free survival response in a third or fourth line setting that was similar to what is seen in a first line setting, which is remarkable given the characteristics of the patients.

Comment: There are no treatment options for NSCLC patients with the T790M resistance mutation.Rociletinib is competing with AZD 9291 which so far, has comparable efficacy to the Clovis drug but until final progression free survival is known the difference between the drugs may be determined on safety profiles. In the AURA study AZD 9291 showed PFS of 13.5 months.