Virtual Library
Start Your Search
G. Lee
Author of
-
+
P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P2.01-087 - A Phase 1 Trial Combining Plinabulin and Nivolumab for Metastatic Squamous NSCLC (ID 602)
09:30 - 09:30 | Author(s): G. Lee
- Abstract
Background:
Plinabulin (P) is a microtubule-depolymerizing agent that inhibits tumor growth by targeting both angiogenesis and tumor vasculature as well as directly by inducing apoptosis via the Ras-JNK pathway. It also could activate anti-tumor immunity via inducing maturation of dendritic cells. Pinabulin at 30 mg/m2 given on days 1 and 8 was studied in a randomized phase 2 study in combination with docetaxel 75 mg/m2. Despite the fact that ITT overall survival (OS) was not statistically different between both arms, duration of response was notably longer in DP compared to D, 12.7 months vs 1.5 month in the 30 cohort ( p=0.049). Nivolumab (Nivo) is the first PD-1 inhibitor approved by the FDA in metastatic squamous NSCLC, based on results of a phase III trial showing that patients receiving Nivo lived, on average, 3.2 months longer than patients receiving standard ChRx. Microtubule-depolymerizing agents are known to induce dendritic cell maturation and synergize with immune checkpoint inhibitors in immune competent cancer models. Therefore we hypothesize that combining plinabulin with nivolumab will enhance the immune response which will in turn lead to a higher response rate (RR) and longer OS in patients with metastatic squamous NSCLC.
Methods:
This is a phase I open-label, dose escalation study of plinabulin in combination with nivolumab (PNivo) in patients with metastatic squamous NSCLC that have progressed through one line of platinum-containing ChRx. The primary objectives are safety and tolerability of combination therapy to define the maximum tolerated dose (MTD), dose limiting toxicities (DLT) and/or RP2D for PNivo. The secondary objective is the efficacy of PNivo in terms of RR, progression free survival and OS in the expanded cohort. Plinabulin will be escalated from the biologically active dose of 13.5 mg/m2 using a “3+3” design. At the MTD or highest dose level in this study, the cohort will be expanded as applicable to ensure a total of 9 subjects are treated at the RP2D. Correlative studies to investigate pharmacodynamical effects will be performed. Main inclusion criteria are histologically documented metastatic squamous NSCLC with measurable disease, EGFR/ALK and ROS-1 negativity, ECOG status 0 to 2, preserved organ and marrow function. Main exclusion criteria are untreated brain metastases, concurrent radiation and systemic therapy within 21 days of the first dose of study drug.
Results:
not applicable
Conclusion:
not applicable
