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G. Durm
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P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-011 - A Phase II Trial of Concurrent Chemoradiation with Consolidation Pembrolizumab in Unresectable Stage III Non-Small Cell Lung Cancer (ID 2487)
09:30 - 09:30 | Author(s): G. Durm
- Abstract
Background:
Outcomes for patients with locally advanced non-small cell lung cancer (NSCLC) are poor, and the landscape of treatment in this disease has not changed considerably over the last several years. In those patients with unresectable stage IIIA/IIIB tumors, concurrent chemoradiation has become the standard of care in fit patients, and no alternative approach including induction, consolidation, or maintenance chemotherapy, has been shown to improve overall survival (OS). New treatment paradigms are desperately needed in this setting. Pembrolizumab is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor on regulatory T-cells (T-reg) and inhibits its interaction with its ligands, PD-L1 and PD-L2. PD-1 exerts an inhibitory effect on T-regs, and blocking this pathway allows for enhanced T-reg activity and an improved anti-tumor immune response. In a phase I trial of previously treated NSCLC patients, Pembrolizumab was well tolerated and demonstrated a 21% response rate by RECIST criteria. Furthermore, preclinical data suggests that the combination of radiation therapy and immunotherapy may have additive or even synergistic effects. Based on these findings, we proposed a phase II trial of consolidation Pembrolizumab following concurrent chemoradiation for patients with inoperable or unresectable stage IIIA or IIIB NSCLC.
Methods:
This study is a multi-institutional phase II trial investigating the PD-1 inhibitor Pembrolizumab as consolidation therapy following initial concurrent chemoradiation in patients with unresectable or inoperable stage IIIA/IIIB NSCLC. Concurrent chemoradiation is defined as platinum-based chemotherapy (Cisplatin/Etoposide or Carboplatin/Paclitaxel) that overlaps with radiotherapy (total dose of 59.4-66Gy). Patients must demonstrate stable disease or disease response following chemoradiation and must have no evidence of metastatic disease. Patients who qualify will receive Pembrolizumab at a dose of 200mg IV every 3 weeks starting a minimum of 4 weeks and a maximum of 8 weeks after completion of chemoradiation. The primary endpoint will be time to distant metastatic disease, defined as disease recurrence outside of the radiated field. Secondary endpoints will include progression free survival (PFS), OS, and toxicity. An exploratory objective will involve assessing PD-L1 expression levels in the tumor samples of participating subjects and correlating that with time to metastatic disease, PFS, OS, and treatment toxicity. Approximately 93 patients will be enrolled. The sample size was calculated based on the hypothesis that consolidation Pembrolizumab will improve time to metastatic disease to 18 months from a historical control of approximately 12 months with a power of 0.80 and a type I error of 0.05.
Results:
Accrual for this trial has begun, and the first patient was enrolled in March 2015.
Conclusion:
This study will determine whether immunotherapeutic consolidation with Pembrolizumab will increase the time to metastatic disease in patients with stage IIIA/IIIB NSCLC following concurrent chemoradiation. It will also answer questions about the safety and tolerability of this combination of therapies in this patient population.
