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B.H. Chao
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-005 - Phase 1 Study of Ramucirumab or Necitumumab in Combination with Osimertinib (AZD9291) in Advanced T790M-Positive EGFR-Mutant NSCLC (ID 4278)
14:30 - 14:30 | Author(s): B.H. Chao
- Abstract
Background:
Despite the likelihood of an initial response to 1st or 2nd generation EGFR-TKI, EGFR mutant patients develop disease progression. The most frequent mechanism of acquired resistance is the EGFR T790M gatekeeper mutation. Novel treatment options are needed in this treatment resistant patient population. Osimertinib, a third-generation EGFR TKI targeting mutant EGFR including T790M, is an oral, irreversible, selective inhibitor. Ramucirumab and necitumumab are human IgG1 monoclonal antibodies to VEGFR-2 and EGFR, respectively. This phase 1, open-label, multicenter study with expansion cohorts (JVDL; NCT02789345) is designed to evaluate the safety and preliminary efficacy of ramucirumab or necitumumab in combination with osimertinib in patients with advanced EGFR T790M-positive NSCLC who have progressed after EGFR TKI therapy.
Methods:
This study includes patients with advanced or metastatic EGFR T790M-positive EGFR activating mutant (exon 19 deletions or L858R) NSCLC, with measurable disease and ECOG performance status 0-1 who have experienced disease progression on one prior EGFR TKI regardless of prior chemotherapy. Patients previously treated with an EGFR antibody or 3rd generation EGFR TKI for NSCLC are not eligible. In the phase 1a dose de-escalation portion (3+3 design), all patients (n=6 to 24) will be administered daily oral osimertinib (80 mg) with either an initial dose of 10 mg/kg IV ramucirumab on day 1 of every 2-week cycle or 800 mg IV necitumumab on days 1 and 8 of every 3-week cycle. One level of dose de-escalation is planned for each arm. A dose reduction (level -1) to 8 mg/kg IV ramucirumab or 600 mg IV necitumumab is planned if 2 or more patients have DLTs in either arm. After the DLT evaluation, the study will open a dose-expansion portion (phase 1b) and 25 patients in each Arm will receive study treatment until disease progression or a criterion for discontinuation is met. The primary objective is to assess safety and tolerability of ramucirumab or necitumumab in combination with osimertinib. Secondary endpoints include preliminary efficacy and pharmacokinetics. An exploratory biomarker objective includes the assessment of correlations between EGFR-mutations in tissue and serial blood samples with clinical outcomes. Primary analyses will be conducted approximately 6 months after the last patient receives initial dose.
Results:
Section not applicable
Conclusion:
Section not applicable
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P2.06-016 - Phase 2 Study of Ramucirumab plus Weekly Docetaxel in Stage IV NSCLC Following Progression after Platinum-Based Chemotherapy (ID 4614)
14:30 - 14:30 | Author(s): B.H. Chao
- Abstract
Background:
Ramucirumab, a human IgG1 monoclonal antibody, binds to vascular endothelial growth factor (VEGF) receptor 2, competing with VEGF-A, -C and –D and thereby preventing receptor activation and angiogenesis. The phase 3 REVEL trial demonstrated the addition of ramucirumab to docetaxel improved survival in patients with stage IV NSCLC following progression after platinum-based chemotherapy, independent of histology. The approved dose of docetaxel in NSCLC patients after progression on prior platinum-based chemotherapy is 75 mg/m2 every 3 weeks. The most common toxicity associated with this dosing regimen is myelosuppression, specifically neutropenia. In order to reduce the incidence of myelosuppression, various weekly docetaxel dosing regimens have been evaluated. These studies have suggested that weekly docetaxel can provide better tolerability with at least similar efficacy. This phase 2, single arm, open-label study (JVDN; NCT02831491) is designed to assess a potential reduction in the rate of grade ≥3 neutropenia and febrile neutropenia with weekly docetaxel in combination with ramucirumab, as compared to historical safety data from the REVEL trial. This study will also assess safety and efficacy of ramucirumab with weekly docetaxel in patients who received prior immunotherapy for NSCLC.
Methods:
Study JVDN includes patients (n=50) with stage IV NSCLC, with measurable disease and ECOG performance status 0-1 who have experienced disease progression from one prior platinum-based therapy which may have included bevacizumab. Prior immunotherapy for NSCLC is permitted. Patients will receive the approved ramucirumab dose regimen for NSCLC (10mg/kg IV) on day 1 every 3 weeks, followed by weekly docetaxel (35 mg/m2 IV) on days 1, 8 and 15 every 4 weeks. Treatment may continue until disease progression or a criterion for discontinuation is met. The primary endpoint is to assess safety, as measured by the rate of grade ≥3 neutropenia (CTCAE v4.0). Secondary endpoints for all patients include the rate of treatment-emergent febrile neutropenia, overall safety, pharmacokinetics (ramucirumab), and efficacy. Additional secondary endpoints of safety and efficacy will be assessed in patients who did or did not receive prior immunotherapy. An exploratory endpoint is to assess the association between biomarkers with safety and clinical outcomes. The primary and final analyses will occur after 31 and 50 patients, respectively, have completed ≥12 weeks of treatment to determine if grade ≥3 neutropenia and febrile neutropenia are reduced with the investigational weekly docetaxel treatment as compared to historical safety data from REVEL.
Results:
Not applicable
Conclusion:
Not applicable
