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 Inhibitors at the 39th SITC Annual Meeting
BeyondSpring (NASDAQ: BYSI) presented updated Phase 2 trial results for a triple combination therapy in non-small cell lung cancer (NSCLC) patients who progressed after PD-1/PD-L1 inhibitor treatment. The study of 30 patients, with a median follow-up of 11.5 months, showed promising results with a disease control rate of 89.3% and median progression-free survival of 8.6 months. The treatment combination of pembrolizumab plus plinabulin/docetaxel achieved a confirmed overall response rate of 21.1% and median duration of response of 11.4 months. The therapy was generally well-tolerated, with 46.7% of patients experiencing grade 3 or higher treatment-related adverse effects.
BeyondSpring (NASDAQ: BYSI) ha presentato i risultati aggiornati della fase 2 di uno studio clinico per una terapia a tripla combinazione in pazienti con carcinoma polmonare non a piccole cellule (NSCLC) che hanno mostrato progressione dopo il trattamento con inibitori di PD-1/PD-L1. Lo studio ha coinvolto 30 pazienti, con un follow-up mediano di 11,5 mesi, mostrando risultati promettenti con un tasso di controllo della malattia dell'89,3% e un tempo mediano di sopravvivenza libera da progressione di 8,6 mesi. La combinazione di trattamento di pembrolizumab più plinabulin/docetaxel ha raggiunto un tasso di risposta complessivo confermato del 21,1% e una durata mediana della risposta di 11,4 mesi. La terapia è stata generalmente ben tollerata, con il 46,7% dei pazienti che ha avuto effetti avversi correlati al trattamento di grado 3 o superiore.
BeyondSpring (NASDAQ: BYSI) presentó resultados actualizados del ensayo de fase 2 para una terapia de combinación triple en pacientes con cáncer de pulmón no microcítico (NSCLC) que progresaron después del tratamiento con inhibidores de PD-1/PD-L1. El estudio incluyó a 30 pacientes, con un seguimiento medio de 11,5 meses, que mostró resultados prometedores con un tasa de control de la enfermedad del 89,3% y una supervivencia libre de progresión mediana de 8,6 meses. La combinación de tratamiento de pembrolizumab más plinabulin/docetaxel logró una tasa de respuesta general confirmada del 21,1% y una duración mediana de respuesta de 11,4 meses. La terapia fue generalmente bien tolerada, con el 46,7% de los pacientes experimentando efectos adversos relacionados con el tratamiento de grado 3 o superior.
BeyondSpring (NASDAQ: BYSI)는 PD-1/PD-L1 억제제 치료 후 진행된 비소세포 폐암(NSCLC) 환자에 대한 삼중 요법의 2상 시험 결과를 업데이트하여 발표했습니다. 30명의 환자를 대상으로 한 이 연구는 11.5개월의 중간 추적 관찰 기간 동안 질병 조절률이 89.3%이고 중간 무진행 생존기간이 8.6개월으로 유망한 결과를 보여주었습니다. pembrolizumab과 plinabulin/docetaxel의 치료 조합은 확인된 전체 반응률이 21.1%이고 반응 지속 기간이 11.4개월로 나타났습니다. 치료는 일반적으로 잘 견뎌졌으며, 환자의 46.7%가 3급 이상의 치료 관련 부작용을 경험했습니다.
BeyondSpring (NASDAQ: BYSI) a présenté les résultats actualisés d'un essai de phase 2 pour une thérapie à trois composants chez des patients atteints de cancer du poumon non à petites cellules (NSCLC) ayant progressé après un traitement par des inhibiteurs de PD-1/PD-L1. L'étude, portant sur 30 patients, avec un suivi médian de 11,5 mois, a montré des résultats prometteurs avec un taux de contrôle de la maladie de 89,3% et une survie sans progression médiane de 8,6 mois. La combinaison de traitement de pembrolizumab avec plinabulin/docetaxel a obtenu un taux de réponse global confirmé de 21,1% et une durée médiane de réponse de 11,4 mois. La thérapie a généralement été bien tolérée, avec 46,7% des patients ayant éprouvé des effets indésirables liés au traitement de grade 3 ou supérieur.
BeyondSpring (NASDAQ: BYSI) hat aktualisierte Ergebnisse der Phase-2-Studie für eine dreifache Kombinationstherapie bei Patienten mit nicht-kleinzelligem Lungenkrebs (NSCLC) vorgestellt, die nach einer Behandlung mit PD-1/PD-L1-Inhibitoren Fortschritte gemacht haben. Die Studie umfasste 30 Patienten mit einer medianen Nachbeobachtungszeit von 11,5 Monaten und zeigte vielversprechende Ergebnisse mit einer Krankheitskontrollrate von 89,3% und einer medianen progressionsfreien Überlebenszeit von 8,6 Monaten. Die Behandlungskombination aus Pembrolizumab und Plinabulin/Docetaxel erreichte eine bestätigte allgemeine Ansprechraten von 21,1% und eine mediane Ansprechdauer von 11,4 Monaten. Die Therapie wurde im Allgemeinen gut vertragen, wobei 46,7% der Patienten schwerwiegende behandlungsbedingte Nebenwirkungen von Grad 3 oder höher aufwiesen.
- Disease control rate of 89.3%, significantly higher than historical controls
- Median progression-free survival of 8.6 months, double the historical 3-4 months
- Overall response rate of 21.1%, higher than comparative TROPION Lung-01 study (12.8%)
- Median duration of response of 11.4 months
- 46.7% of patients experienced grade 3 or higher treatment-related adverse effects
- Most common adverse events included myelosuppression (13.3%), GI side effects (13.3%), and transient hypertension (6.7%)
Insights
The Phase 2 trial results for BeyondSpring's triple combination therapy show promising efficacy in a difficult-to-treat patient population. The 8.6-month median progression-free survival (PFS) represents a significant improvement over historical controls of 3-4 months and the 89.3% disease control rate is particularly noteworthy.
Key comparative data points demonstrate strong potential: The triple combination achieved an 21.1% overall response rate, substantially higher than the 12.8% seen in the recent TROPION Lung-01 study. The safety profile appears manageable, with grade 3+ adverse events in 46.7% of patients, primarily consisting of expected effects like myelosuppression.
The durability of response at 11.4 months and unreached median overall survival suggest potential long-term benefits. This positions plinabulin's unique mechanism of action targeting dendritic cell maturation as a promising approach for overcoming immunotherapy resistance in NSCLC.
In 30 metastatic NSCLC patients who progressed on PD-1/PD-L1 inhibitors, the triple IO combo regimen at median follow-up time of 11.5 months achieved a DCR of
FLORHAM PARK, N.J., Nov. 11, 2024 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, today announced 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's (SITC) Annual Meeting on November 8th, 2024 in Houston, Texas.
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
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),
| Primary Endpoint | Plinabulin + Pembrolizumab + Docetaxel (n=30) |
| Confirmed ORR (RECIST 1.1) | |
| 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) | (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 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
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: Dr. 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, https://doi.org/10.1200/JCO-24-0154
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.
About BeyondSpring
BeyondSpring is a global clinical-stage biopharmaceutical company developing innovative therapies to improve clinical outcomes for patients with high unmet medical needs. The Company is advancing its first-in-class lead asset, Plinabulin, a potent inducer of dendritic cell maturation, in late-stage clinical development as a direct anti-cancer agent in NSCLC and a variety of cancer indications. BeyondSpring’s pipeline also includes three preclinical immuno-oncology assets. Additionally, BeyondSpring is an equity owner of SEED Therapeutics, Inc which is a pioneer in Target Protein Degradation technology and its application in innovative drug development. Learn more by visiting https://beyondspringpharma.com.
Investor Contact:
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