LBA48 - DUBLIN-3 (BPI-2358-103): A global phase (Ph) III trial with the plinabulin/docetaxel (Plin/Doc) combination vs. Doc in 2nd/3rd Line NSCLC patients (pts) with EGFR-wild type (wt) progressing on a prior platinum-based regimen

Background

PD1-i therapy is standard of care in 1^st line, and Doc-based regimens in 2^nd/3^rd line EGFR-wt NSCLC pts. Doc improves survival, however, may negatively impact safety and quality of life (QoL). Plin, a novel immune-enhancing small molecule enhances dendritic cell maturation and T-Cell proliferation. Final survival, safety and QoL data of DUBLIN-3 are reported.

Methods

DUBLIN-3(NCT02504489) was a randomized, single-blinded (pts only), active controlled Ph3 study in 2^nd/3^rd line stage IIIB/IV, EGFR wt NSCLC pts with a measurable lesion (RECIST 1.1) in the lung, and ECOG ≤ 2, conducted in US, Australia and China. Pts (n=559) were randomized 1:1 to Plin/Doc or Doc/Placebo (21 day (D) cycle (C)). Doc (75 mg/m² on D1 and Plin 30 mg/m² on D1 and D8 were given by IV infusion. Primary endpoint was Overall Survival (OS). Secondary endpoints were ORR, PFS, OS rate at 24, 36 months (M), Grade (Gr) 4 neutropenia (N) rate on C1 D8 (N nadir with Doc is on D8), QoL (EORTC QLQ C30, QLQ-LC13), Q-TWiST (a measure integrating Survival, QoL, Safety), and Safety (adverse events (AE).

Results

Baseline characteristics were balanced between both groups. Plin/Doc was well tolerated. Primary and key secondary objectives were met (Table). Investigator-assessed ORR (12.2% versus (vs) 6.8%; p=0.0275) and mean PFS (6.0M vs 4.4M; p=0.006); median PFS (3.6 M vs 3.0 M; p=0.008; HR=0.76 (0.63, 0.93) favored Plin/Doc. Q-TWiST with Plin/Doc vs Doc was statistically and clinically better (p=0.026 with relative gain of 18.4%). Gr4 AE rate (95% CI) per year was 1.69 (1.4;2.0) for Plin/Doc and 3.08 (2.7;3.5) for Doc (p<0.001). Table: LBA48

∗All p-values favor Plin/Doc over Doc alone; ∗∗Data based on ITT population, but summarizing OS for pts with ≥4 or ≥8 cycles.

Conclusions

The addition of Plin to Doc resulted in superior overall survival, safety and QoL vs Doc alone, offering 2^nd/3^rd line NSCLC pts the prospect of living longer and well.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

BeyondSpring Pharmaceuticals Inc.

Funding

BeyondSpring Pharmaceuticals Inc.

Disclosure

T. Feinstein: Financial Interests, Personal and Institutional, Advisory Role: Beyond Spring Pharmaceuticals; Financial Interests, Personal and Institutional, Speaker’s Bureau: Beyond Spring Pharmaceuticals. L. Huang: Financial Interests, Personal and Institutional, Stocks/Shares: Beyond Spring Pharmaceuticals; Financial Interests, Personal and Institutional, Ownership Interest: Beyond Spring Pharmaceuticals; Financial Interests, Personal and Institutional, Funding: Beyond Spring Pharmaceuticals; Financial Interests, Personal and Institutional, Royalties: Beyond Spring Pharmaceuticals. R. Mohanlal: Financial Interests, Personal and Institutional, Full or part-time Employment: Beyond Spring Pharmaceuticals; Financial Interests, Personal and Institutional, Stocks/Shares, Beyond Spring Pharmaceuticals: Beyond Spring Pharmaceuticals; Financial Interests, Personal and Institutional, Leadership Role: Beyond Spring Pharmaceuticals. All other authors have declared no conflicts of interest.