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 89.3% and Median PFS of 8.6 months
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 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 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: 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,
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 .
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在30名使用PD-1/PD-L1抑制劑進展的轉移性非小細胞肺癌患者中，中位隨訪時間爲11.5個月的三重IO組合方案實現了89.3％的DCR和8.6個月的中位PFS
新澤西州弗洛勒姆公園，2024年11月11日（GLOBE NEWSWIRE）——開發創新癌症療法的臨床階段全球生物製藥公司BeyondSpring Inc.（納斯達克股票代碼：BYSI）（「BeyondSpring」 或 「公司」）今天宣佈，在303患者研究中首批30名患者服用plinabulin的2期IoT（由研究者發起）數據在11月的第39屆癌症免疫療法學會（SITC）年會上發表了使用PD-1/PD-L1抑制劑治療和不進行化療後疾病進展後的非小細胞肺癌（NSCLC）2024 年 8 日在德克薩斯州休斯敦舉行。
對於沒有靶向改變的2L/3L NSCLC患者，在使用免疫檢查點抑制劑（ICI）時，無論是否接受標準化療，多西他賽仍然是治療的標準。在最近的TROPION Lung-01 3期研究中，類似的患者群體的總緩解率（ORR）爲12.8％，中位PFS（MPF）爲3.7個月。在對先前的 PD-1/L1 療法產生耐藥性的轉移性非小細胞肺癌中，單獨抑制 PD-L1 和 CTLA-4 或與低分餾放射治療聯合使用產生的臨床益處有限，ORR 約爲 11.5%。
這項由研究者發起的單臂、開放標籤的2期研究（keypelms-004或303研究）評估了pembrolizumab和plinabulin/docetaxel（NCT05599789）三聯療法的療效和安全性。該研究旨在共招收47名患者，目前正在中國北京協和醫院進行，首席研究員王孟照博士，呼吸與重症醫學系主任。在這裏，我們報告了30名患者的最新結果。
在 2024 年 8 月 29 日的數據庫鎖定中，有 36 名患者入組，其中 30 名患者接觸了 plinabulin 方案。在入院之前，所有患者在ICI的初始臨床受益後都經歷了疾病進展。在30名接受治療的患者中（平均年齡爲68.0歲；介於50-77歲之間），73.3％爲男性，26.7％爲女性；60％爲現任或以前的吸菸者。組織學包括 57% 的非鱗狀細胞癌患者和 43%（n=13）的鱗狀細胞癌患者。中位隨訪時間爲11.5個月。以下是功效彙總表：
| 主終端節點 | Plinabulin + Pembrolizumab + 多西他賽 (n=30) |
| 已確認的 ORR (reCist 1.1) | 21.1% |
| 輔助終端節點 | |
| PFS 中位數 (reCist 1.1) | 8.6 米 |
中位操作系統
（總體生存） | 未到達 |
DoR 中位
（回覆時長） | 11.4 米 |
疾病控制率
（PR + SD > 4 個月） | 89.3%
（25/28 — 2 名患者在第一次給藥後退出） |
- 該組合的耐受性總體良好。46.7％的患者出現了3級或更高的治療相關不良反應。最常見的不良反應是骨髓抑制（13.3%）、胃腸道副作用（13.3%）和短暫性高血壓（6.7%）。沒有與治療相關的死亡。
- 結果與9月份ESMO第303號研究中報告的前19名患者的數據一致。
「Plinabulin是樹突狀細胞或直流成熟的有效誘導劑，可激活T細胞。DC 是最有效的抗原呈遞細胞 (APC)。這種獨特的作用機制增強了抗腫瘤免疫反應，有可能克服獲得性ICI耐藥性，這種耐藥性可能源於APC通路改變或T細胞衰竭。與歷史對照組中位數爲3-4個月的PFS2相比，30名患者的療效數據在8.6個月時保持了PFS中位數的兩倍，而且令人印象深刻的疾病控制率接近90％，對於這種嚴重的未滿足的需求，這仍然令人鼓舞，具有臨床意義。」 北京協和醫院首席研究員王孟照博士說。
SITC 2024 摘要標題：Pembrolizumab（pemb）與普利納布林（plin）和多西他賽（doc）在一線免疫檢查點抑制劑單獨或聯合療法失敗後用於轉移性非小細胞肺癌的2期研究：更新的免疫再敏化療效和安全結果
- 主講作者：徐燕博士，北京協和醫院
- 摘要編號：1491
參考文獻：
- 舍恩菲爾德等人，2022年，《柳葉刀腫瘤學》23:279-291
- Ahn 等人。2024，TROPION Lung-01 研究，《臨床腫瘤學雜誌》，
關於 Plinabulin
Plinabulin是一種新型的首創樹突狀細胞成熟療法，在多項臨床研究中觀察到具有持久的抗癌功效。作爲不同微管蛋白袋中的可逆粘合劑，plinabulin不會改變微管蛋白的動力學或拮抗微管蛋白穩定劑，例如多西他賽，與其他微管蛋白粘合劑相比，多西他賽有助於其差異化的活性和耐受性。此外，plinabulin可顯著減少化療引起的中性粒細胞減少症，從而提高多西他賽的耐受性。大約有800名患者接受了具有良好耐受性的普利納布林治療。
關於 303 研究
303研究是一項開放標籤、單臂的Plinabulin聯合多西他賽和pembrolizumab的2期研究，用於先前接受過治療的轉移性非小細胞肺癌和單獨使用抗PD-（L）1抑制劑或與鉑雙聯化療聯合治療的進展性疾病患者。這項研究評估了這種三聯組合的療效和安全性，正在中國北京協和醫院進行。該方案包括在第1天每3周（Q3W）靜脈注射200毫克的Pembrolizumab，第一天的多西他賽75 mg/m2 IV Q3W，以及在第一天以21天爲週期的Plinabulin 30mg/m2 IV Q3W。主要終點是基於研究者的ORR（reCist 1.1）。輔助終端包括 PFS、操作系統、DoR 和安全。該研究旨在招收47名患者。該研究由默克研究計劃資助，提供研究藥物和財政支持。
關於 BeyondSpring
BeyondSpring是一家全球臨床階段的生物製藥公司，開發創新療法，以改善醫療需求未得到滿足的患者的臨床療效。作爲非小細胞肺癌和各種癌症適應症的直接抗癌藥物，該公司正在推進其首創的主導資產——樹突狀細胞成熟的強效誘導劑Plinabulin的後期臨床開發。BeyondSpring的產品線還包括三項臨床前免疫腫瘤學資產。此外，BeyondSpring還是SEED Therapeutics, Inc的股權所有者，該公司是靶蛋白降解技術及其在創新藥物開發中的應用的先驅。訪問以了解更多信息。
投資者聯繫人：
IR@beyondspringpharma.com
媒體聯繫人：
PR@beyondspringpharma.com
