On November 11, 2024 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, reported that phase 2 IIT (Investigator-initiated) data on the first 30 patients dosed with plinabulin in the 303 Study of patients with non-small cell lung cancer (NSCLC) after disease progression on PD-1/PD-L1 inhibitors with and without chemotherapy were presented at the 39th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting on November 8th, 2024 in Houston, Texas (Press release, BeyondSpring Pharmaceuticals, NOV 11, 2024, View Source;utm_medium=rss&utm_campaign=beyondspring-presents-updated-efficacy-results-from-a-phase-2-iit-study-of-triple-io-combo-of-pembrolizumab-plus-plinabulin-docetaxel-in-metastatic-nsclc-after-progressing-on-prior-immune-checkpoint-i [SID1234648068]).
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Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations who progress on immune checkpoint inhibitors (ICI) with and without standard chemotherapy. In the recent TROPION Lung-01 phase 3 studies, a similar patient population had an overall response rate (ORR) of 12.8% and median PFS (mPFS) of 3.7 months. In metastatic NSCLC resistant to previous PD-1/L1 therapy1, PD-L1 and CTLA-4 inhibition alone or in combination with hypofractionated radiotherapy produced limited clinical benefits with ~11.5% ORR.
This investigator-initiated, single-arm, open-label, phase 2 study (KeyPelms-004 or 303 Study) evaluates the efficacy and safety of a triple combination regimen of pembrolizumab plus plinabulin/docetaxel (NCT05599789). The study intends to enroll a total of 47 patients and is ongoing at Peking Union Medical College Hospital, Beijing, China with the principal investigator Dr. Mengzhao Wang, Chief of the Department of Respiratory and Critical Care Medicine. Here, we report on updated results from 30 patients.
At the database lock on 29 August 2024, 36 patients were enrolled, 30 exposed to the plinabulin regimen. Prior to entry, all patients had experienced disease progression after initial clinical benefit with ICI. Of the 30 treated patients (median age at 68.0 years; ranged 50-77 years), 73.3% were male and 26.7% were female; 60% were current or former smokers. Histology included 57% patients (n=17) with non-squamous cell carcinoma and 43% (n=13) with squamous cell carcinoma. The median follow-up was 11.5 months. Below is an efficacy summary table:
Primary Endpoint Plinabulin + Pembrolizumab + Docetaxel (n=30)
Confirmed ORR (RECIST 1.1) 21.1%
Secondary Endpoints
Median PFS (RECIST 1.1) 8.6 M
Median OS
(Overall Survival)
Not reached
Median DoR
(Duration of Response)
11.4 M
Disease Control Rate
(PR + SD > 4 months)
89.3%
(25/28 – 2 patients withdrew after first dose)
The combination was generally well tolerated. 46.7% of patients experienced grade 3 or higher treatment-related adverse effects. Most common AE is myelosuppression (13.3%), GI side effect (13.3%), and transient hypertension (6.7%). There were no treatment-related deaths.
Results are consistent with the data reported on the first 19 patients in Study 303 at ESMO (Free ESMO Whitepaper) in September
"Plinabulin is a potent inducer of dendritic cell or DC maturation that leads to T cell activation. DCs are the most potent antigen presenting cell (APC). This unique mechanism of action reinforces anti-tumor immune response with the potential to overcome acquired ICI resistance, which may derive from APC pathway alteration or T cell exhaustion. Compared to historical controls of 3-4 months of median PFS2, the efficacy data with 30 patients maintained a doubled median PFS at 8.6 months, coupled with an impressive disease control rate of almost 90%, which continues to be encouraging and clinically meaningful for this severe unmet need," said Dr. Mengzhao Wang, principal investigator at Peking Union Medical College Hospital.
SITC 2024 Abstract Title: Phase 2 Study of Pembrolizumab (pemb) plus Plinabulin (plin) and Docetaxel (doc) for Metastatic NSCLC after Failure on First-line Immune Checkpoint Inhibitor Alone or Combination Therapy: Updated Efficacy and Safety Results on Immune Re-sensitization
Presenting Author: Yan Xu, Peking Union Medical College Hospital
Abstract Number: 1491
References:
Schoenfeld et al. 2022, Lancet Oncology 23:279-291
Ahn et al. 2024, TROPION Lung-01 Study, Journal of Clinical Oncology, View Source
About Plinabulin
Plinabulin is a novel first-in-class dendritic cell maturation therapeutic with durable anti-cancer benefit observed across multiple clinical studies. As a reversible binder at a distinct tubulin pocket, plinabulin does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel, which contributes to its differentiated activity and tolerability compared to other tubulin binders. In addition, plinabulin significantly reduces chemotherapy induced neutropenia and could thereby increase docetaxel tolerability. Around 800 patients have been treated with plinabulin with good tolerability.
About 303 Study
303 Study is an open-label, single-arm Phase 2 Study of Plinabulin plus docetaxel and pembrolizumab for previously treated patients with metastatic NSCLC and progressive disease after anti-PD-(L)1 inhibitor alone or in combination with platinum-doublet chemotherapy. This study evaluates the efficacy and safety of this triple combination and is being conducted at Peking Union Medical College Hospital, Beijing, China. The regimen includes Pembrolizumab 200 mg IV every 3 weeks (Q3W) on Day 1, Docetaxel 75 mg/m2 IV Q3W on Day 1 and Plinabulin 30mg/m2 IV Q3W on Day 1 in a 21-day cycle. The primary endpoint is investigator-based ORR (RECIST 1.1). The secondary endpoints include PFS, OS, DoR, and safety. The study intends to enroll 47 patients. The study is funded by Merck’s Investigator Studies Program with provision of study drug and financial support.