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J. Isaacson



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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 2
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      P1.01-076 - TIGER-1: A Phase 2/3 Study of First Line Rociletinib or Erlotinib in EGFR-Mutant NSCLC (ID 944)

      09:30 - 17:00  |  Author(s): J. Isaacson

      • Abstract

      Background:
      Activating EGFR mutations including the L858R mutation and exon 19 deletions (del19) are key drivers of non-small cell lung cancer (NSCLC) in 10%–15% of patients of European and 30%–35% of Asian descent.[1] Acquired resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib can be driven by additional EGFR mutations, with exon 20 T790M accounting for 50%–60% of cases.[2] Rociletinib (CO-1686) was designed to inhibit T790M as well as L858R and del19 while sparing wild-type EGFR and has demonstrated response rates up to 67% in patients with T790M mutations who had progressed on first or later line EGFR inhibitor therapy. Rociletinib continues to be well tolerated by patients in ongoing studies.[3] Given that T790M mutated subclones commonly emerge during treatment with existing EGFR inhibitors, early targeting of T790M along with initial activating mutations is a rational approach to delay progression.

      Methods:
      TIGER-1 (NCT02186301) is a randomized, open label study of rociletinib vs erlotinib in patients with mutant EGFR NSCLC. Patients with histologically or cytologically confirmed metastatic or unresectable locally advanced treatment-naive NSCLC (no prior therapy in the metastatic setting and no CNS disease), with documentation of ≥1 activating EGFR mutation (excluding exon 20 insertions) and biopsy within 60 days will be enrolled in this 2-part study. All patients will be randomized 1:1 to rociletinib (500 mg twice daily) or erlotinib (150 mg once daily) and treated until death, qualifying adverse events or disease progression. Patients will be stratified by sensitizing EGFR mutation (T790M, del19, L858R, or other) and territory (Asian vs non-Asian geography). The same patient eligibility criteria will be used for the Phase 2 and Phase 3 portions of TIGER-1. The phase 2 portion is currently enrolling and will transition to the Phase 3 portion upon enrollment of the 201[st] patient. The maturing Phase 2 dataset will contribute to decision-making rules for the Phase 3 interim analyses. The Phase 3 portion will incorporate larger cohorts; the final sample sizes will be determined by interim analyses where the chances of success will be estimated at pre-planned enrollment milestones. The primary endpoint is PFS; secondary efficacy endpoints include objective response rate, duration of response, disease control rate and overall survival. Safety will be assessed via standard adverse event reporting. PFS and OS will be summarized with Kaplan-Meier plots. The stratified log-rank and hazard ratio will compare PFS distributions for rociletinib- vs erlotinib-treated patients. Enrollment is ongoing. 1. Herbst R et al. N Engl J Med. 2008 2. Yu H et al. Clin Cancer Res. 2013 3. Sequist LV J Clin Oncol. 2014

      Results:
      Not applicable

      Conclusion:
      Not applicable

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      P1.01-086 - TIGER-3: A Phase 3 Open-Label, Randomized Study of Rociletinib vs Chemotherapy in NSCLC (ID 949)

      09:30 - 17:00  |  Author(s): J. Isaacson

      • Abstract
      • Slides

      Background:
      Rociletinib (CO-1686) is a novel, oral, irreversible tyrosine kinase inhibitor for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) that has demonstrated efficacy against the activating mutations (L858R and Del19) and the dominant acquired resistance mutation (T790M), while sparing wild-type EGFR. TIGER-X, a Phase I/II dose-ranging trial, has provided evidence that rociletinib is associated with durable response and is well tolerated in patients with NSCLC and positive T790M status following progression on a TKI.[1 ]Efficacy has also been noted for patients with T790M negative status in TIGER-X.[2] TIGER-3 is designed to investigate single agent rociletinib vs chemotherapy in patients who have failed EGFR therapy and platinum-based doublet chemotherapy, which is a setting of acquired resistance and high unmet need for targeted therapeutic options. TIGER-3 will evaluate patients with T790M positive and negative status based on tumor biopsies and plasma, and biomarkers of response and/or resistance.

      Methods:
      Patients with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC, with radiological progression on the most recent therapy will be enrolled in this phase 3, randomized, open-label study (NCT02322281). Patients must have documented evidence of a tumor with ≥1 EGFR activating mutations excluding exon 20 insertion, and prior treatment with an EGFR TKI and platinum-containing doublet chemotherapy. Patients will be randomized 1:1 to receive rociletinib twice daily (500 mg) or single agent cytotoxic chemotherapy (investigator choice specified before randomization) until disease progression according to RECIST 1.1. Patients will be stratified by presence or absence of brain metastases, ECOG performance status (0 vs 1), and race (Asian vs non-Asian). The primary endpoint is progression-free survival (PFS). Secondary endpoints include safety, objective response rates, duration of response, disease control rate, and overall survival. Kaplan-Meier methodology will assess time to event variables. The stratified log-rank and the hazard ratio will be used for comparing PFS distributions. Serial assessment of safety will be carried out based on standard adverse event reporting. Planned enrolment is 600 patients; enrolment has been open since March 2015. Sequist LV J Clin Oncol. 2014 Soria J-C EORTC-NCI-AACR 2014

      Results:
      Not applicable

      Conclusion:
      Not applicable

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