Locally Advanced or Metastatic Non Small Cell Lung Cancer Clinical Trial
Official title:
A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)
Rociletinib is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer
accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with
NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted
therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have
mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the
gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually
progress, and in approximately 50% of cases, progression is due to development of an
additional mutation called T790M. There are currently no approved therapies for patients who
progress on TKIs. Rociletinib may provide an effective therapy for a patient population with
few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits
T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the
T790M mutation, thus providing possible therapeutic benefit in patients who have developed
T790M-mediated resistance to first generation TKIs.
This is a two-part, open-label study of oral rociletinib administered daily in previously
treated NSCLC patients who have documented evidence of an activating mutation in the EGFR
gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or
afatinib.
This study will include 2 parts:
Phase 1: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period
starting on Day 22
Phase 2: Evaluation of activity and safety in patients with the T790M EGFR mutation who have:
Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of
previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR
directed therapy received and also had no more than one previous line of chemotherapy or
Cohort C - Patients with discordance between local (T790M positive) and central (T790M
negative) T790M results, or had no central test result due to inadequacy of the tissue
specimen and known to be T790M positive by local test
;