PD1-i therapy is standard of care in 1st line, and Doc-based regimens in 2nd/3rd 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.
DUBLIN-3(NCT02504489) was a randomized, single-blinded (pts only), active controlled Ph3 study in 2nd/3rd 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).
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
|ITT Population||OS (mean)||OS (median)||OS**: pts with ≥4 cycles (median)||OS**: pts with ≥8 cycles (median)||OS rate 24M||OS rate 36M||OS rate 48M||Gr4 Neutro-penia rate||Q-TWiST (95% CI)||Gr3/4 AE rate/pt/ year (95% CI)|
|Plin/Doc (n=278)||15.1 M||10.5 M||18.3 M (n=133)||28.2 M (n=45)||22.1%||11.7%||10.6%||5.3%||12.4 M (11.0, 13.8)||9.9 (9.2, 10.5)|
|Doc (n=281)||12.8 M||9.4 M||13.5 M (n=128)||19.3 M (n=31)||12.5%||5.3%||0%||27.8%||10.5 M (9.3, 11.6)||10.9 (10.2, 11.7)|
|p-value*||0.0332||0.0399 HR: 0.82 (0.68,0.99)||0.0022 HR: 0.63 (0.47,0.85)||0.0121 HR: 0.45 (0.24,0.85)||0.0072||0.0393||NA||<0.001||0.0263||0.0381|
∗All p-values favor Plin/Doc over Doc alone; ∗∗Data based on ITT population, but summarizing OS for pts with ≥4 or ≥8 cycles.
The addition of Plin to Doc resulted in superior overall survival, safety and QoL vs Doc alone, offering 2nd/3rd line NSCLC pts the prospect of living longer and well.
Clinical trial identification
Legal entity responsible for the study
BeyondSpring Pharmaceuticals Inc.
BeyondSpring Pharmaceuticals Inc.
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.