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L. Huang
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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)
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P2.01-101 - Randomized Phase 3 Trial of Docetaxel+Plinabulin Compared to Docetaxel in Advanced Non-Small Cell Lung Cancer with at Least 1 Large Lung Lesion (ID 1498)
09:30 - 09:30 | Author(s): L. Huang
- Abstract
Background:
Plinabulin (BPI-2358) is a marine derived tubulin binding agent, which inhibits existing tumor vasculature and directly induces cancer cell apoptosis via the Ras-JNK pathway. Additional effect of inducing dendritic cell maturation is also observed. Phase 1/2 randomized clinical trial of Docetaxel + Plinabulin (DP) compared to Docetaxel (D) alone failed to show improvement in OS in an ITT analysis. The median OS was 8.6 months in DP, and 7.5 months in D arm. (HR 0.97, P=0.90). However, post hoc subset analysis showed improvement in OS in patient with pulmonary tumors >3 cm regardless of number of prior therapy for metastatic disease. In this population, OS was 11.47 (7.13, 16.73) months vs. 7.10 (4.06, 10.60) in DP vs D arm (HR 0.76 and P=0.36). Mechanistically it is postulated that those patients are more dependent on angiogenesis. This phase 3 protocol is designed to test the hypothesis generated from the subset analysis.
Methods:
This is a randomized phase 3, open label clinical trial comparing DP at 75 mg/m2 of D on day1 and 30 mg/m2 of P on days 1 and 8 to D alone at 75 mg/m2 on day 1 in a 21-day cycle. Randomization stratified by ECOG performance status and region. Study population: patients with metastatic with non small cell lung cancer ( NSCLC), who has failed one line of chemotherapy and have at least one lung lesion larger than 3 cm. Primary endpoint of the study is to compare overall survival (OS) between two arms. Secondary endpoints are Progression free survival (PFS), overall response rate (ORR), duration of response (DOR), and adverse event profile. Planned number of subjects 550 (440 from China and 110 from the US). Primary outcome analysis is planned after 434 death events which will provide a 0.85 power to detect a statistically significant treatment effect using a two-sided log-rank test at a significance level of α = 0.05.
Results:
Not applicable, trial in progress.
Conclusion:
not applicable
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-057 - Randomized Phase 2 Study of Plinabulin and Docetaxel in Patients with Advanced Non-Small Cell Lung Cancer - Mechanism-Based Efficacy Analyses (ID 1505)
09:30 - 09:30 | Author(s): L. Huang
- Abstract
Background:
Plinabulin (N), a tubulin binding agent, which depolarizes microtubules, resulting in tumor vasculature obliteration, apoptosis via JNK pathway and maturation of dendritic cells. A multicenter randomized phase 2 study was performed to compare overall survival (OS) between plinabulin/docetaxel (DN) and docetaxel (D). Results of Intent-to-treat (ITT) analyses have been presented at ASCO 2014. The primary objective of OS prolongation was not met, however, exploratory mechanism based analysis revealed improvement in outcomes in patients with large tumors.
Methods:
From November 2008 to July 2011 172 patients with advanced NSCLC who progressed after at least one chemotherapy were enrolled. Patients were treated with D 75mg/m[2] on day 1 and N 30 mg/[2] on days 1 and 8. A second cohort of N 20 mg/m[2] was also enrolled. This exploratory analysis is based on 105 patients (50 DN arm and 55 D arm) receiving 30 mg/m[2] dose, which was selected for an ongoing Phase 3 study and explains the population chosen for future investigation.
Results:
Median OS was 8.7 months (m) (CI 6.6-12.6) in DN arm and 7.5 m (6.3-10.5) in D arm (p=0.899, HR=0.97). PFS was 2.8 m and 3.5 m and ORR was 14.0% vs 14.5% respectively. Among clinical parameters, lesion size (Table 1) and presence of pulmonary disease were identified to impact OS. The OS in patients with pulmonary disease was 11.3 m (6.7-15.1) in DN and 6.7 m (6-9.8) in D, respectively (p=0.29, HR=0.76) regardless of lesion size. Table 1: Exploratory Analysis of Overall Survival by Tumor Size
CI = confidence interval; D = docetaxel; DN, docetaxel + plinabulin; ITT = intent-to-treat; OS = overall survival (Months).Patients Tumor size Median OS Months (95% CI) Hazard Ratio P-value DN (30mg/m[2]) D ITT 1 and 2 prior chemo-therapy All 8.68 (6.33, 12.63) N=50 7.47 (6.17, 10.60) N=55 0.972 0.8993 ≤ 3 cm 6.45 (3.73, NA) N=16 6.47 (5.6, 22.43) N=19 0.934 0.8687 > 3 cm 8.98 (6.60, 12.63) N=34 7.47 (4.77, 11.60) N=36 0.967 0.8990 > 5 cm 8.98 (4.57, 19.23) N= 20 6.70 (4.07, 12.93) N=21 0.750 0.4176 > 7 cm 7.32 (4.57, 19.23) N= 8 5.03 (2.93, 6.70) N= 10 0.507 0.1936
Conclusion:
Mechanism-based exploratory analyses of Phase 2 results have identified advanced NSCLC patients with lung lesion size >3 cm to have benefited from plinabulin. A Phase 3 to confirm this observation is on-going.
