ITeos Announces Clinically Meaningful Objective Response Rate Observed at Every Dose in Follow-up Interim Analysis of GALAXIES Lung-201 Study of Belrestotug + Dostarlimab in First-Line, PD-L1 High Non-Small Cell Lung Cancer Patients
ITeos Announces Clinically Meaningful Objective Response Rate Observed at Every Dose in Follow-up Interim Analysis of GALAXIES Lung-201 Study of Belrestotug + Dostarlimab in First-Line, PD-L1 High Non-Small Cell Lung Cancer Patients
- Clinically meaningful objective response rate (ORR) of 63.3-76.7% observed with belrestotug + dostarlimab combinations, with confirmed ORR (cORR) at ~60% for every dose
->30% cORR difference between belrestotug + dostarlimab vs dostarlimab monotherapy
- Belrestotug + dostarlimab safety profile broadly consistent with known safety profile of checkpoint inhibitor combinations
- GALAXIES Lung-301, global Phase 3 registration study, enrolling in same indication and setting
- iTeos to host a conference call on Monday, September 16, 2024 at 8:00am ET
- 觀察到belrestotug + dostarlimab組合治療具有63.3-76.7%的臨床意義的客觀反應率（ORR），每個劑量的確診ORR（cORR）約爲60%
- belrestotug + dostarlimab與dostarlimab單藥相比，cORR差異超過30%
- belrestotug + dostarlimab的安全概況與已知的檢查點抑制劑組合療法的安全概況基本一致
- GALAXIES Lung-301是全球3期註冊研究，正在同一適應證和環境中進行入組
- iTeos將於2024年9月16日上午8:00舉行電話會議
WATERTOWN, Mass. and GOSSELIES, Belgium, Sept. 14, 2024 (GLOBE NEWSWIRE) -- iTeos Therapeutics, Inc. (Nasdaq: ITOS) ("iTeos"), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, today announced follow-up interim data from GALAXIES Lung-201, the Phase 2 platform study sponsored by iTeos' development partner GSK, assessing the belrestotug + dostarlimab doublet in previously untreated, unresectable, locally advanced or metastatic PD-L1 high non-small cell lung cancer (NSCLC).
麻省沃特敦和比利時戈塞利斯，2024年9月14日（環球新聞）--iTeos Therapeutics, Inc.（納斯達克：ITOS）（「iTeos」）是一家臨床階段生物製藥公司，致力於爲患者開發新一代免疫腫瘤治療藥物的發現和開發，今天宣佈了GALAXIES Lung-201的後續中期數據，該研究由iTeos的發展合作伙伴GSk贊助，評估了belrestotug + dostarlimab雙藥聯合治療PD-L1高表達的非小細胞肺癌（NSCLC）的未經手術的局部晚期或轉移性初治患者。
"We are encouraged by this interim cut of GALAXIES Lung-201 data in which a clinically meaningful, investigator-assessed Objective Response Rate was observed with belrestotug in combination with dostarlimab in first-line, PD-L1 high non-small cell lung cancer patients. Further, with roughly 60 percent confirmed ORR at three distinct doses and a meaningful difference of 30 percent compared to dostarlimab alone, we believe this underscores the potential differentiation of our TIGIT:PD-1 doublet," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "The improvement in depth of response in tumor measurement in patients treated with the doublet compared to those treated with PD-1 alone holds promising therapeutic potential for a patient population with limited options. We believe these encouraging data further support the recent initiation of GALAXIES Lung-301, the registrational Phase 3 trial assessing the TIGIT:PD-1 doublet in the same indication and setting. Based on these results, we are committed to leveraging our science to impact the lives of people living with cancer and are excited to see longer-term follow-up data in 2025."
「我們對GALAXIES Lung-201的中期數據感到鼓舞，觀察到belrestotug與dostarlimab聯合治療一線PD-L1高表達的非小細胞肺癌患者具有臨床意義的調查者評估的客觀反應率。此外，三個不同劑量中大約60%的確診ORR以及與dostarlimab單藥相比有30%的顯著差異，我們相信這突顯了我們TIGIT:PD-1雙藥的潛在差異化。對於治療選擇有限的患者群體而言，雙藥聯合治療在腫瘤測量的療效改善方面具有有希望的治療潛力。根據這些數據，我們致力於利用我們的科學影響癌症患者的生活，並期待在2025年看到更長期的隨訪數據。」iTeos的總裁兼首席執行官Michel Detheux博士說道。
"While checkpoint inhibitor therapies have played a significant role in how we treat non-small cell lung cancer, the medical community continues to look for new patient-centered treatment options to meaningfully improve this life-threatening condition," said Brian Henick, M.D., interim director of experimental therapeutics and director of translational research in upper-aerodigestive malignancies in medical oncology of Columbia University Irving Medical Center. "The follow-up interim analysis from the GALAXIES Lung-201 study represent promising progress and the deep responses observed in the belrestotug + dostarlimab doublet provide a strong, consistent signal. We eagerly anticipate gaining further insights from this trial over the next year as the dataset matures."
「儘管檢查點抑制劑療法在我們治療非小細胞肺癌方面發揮了重要作用，但醫學界繼續尋找新的以患者爲中心的治療選擇，以顯著改善這種威脅生命的控制。」哥倫比亞大學伊利醫學中心實驗治療臨時主任，上呼吸道惡性腫瘤的轉化研究主任Brian Henick萬.D.表示。"GALAXIES Lung-201研究的後續臨時分析展示了令人鼓舞的進展，belrestotug + dostarlimab雙聯療法產生了強烈而一致的深層反應。我們急切期待在未來一年中從這項試驗中獲得更多的見解，隨着數據集的成熟。"
Highlights of Interim GALAXIES Lung-201 Data
As of the June 7, 2024 data cutoff, the late-breaking interim data presented at the ESMO Congress were based on 124 patients eligible for safety and efficacy evaluation (modified intention-to-treat ≥5.6 months follow-up). Patients received dostarlimab or belrestotug + dostarlimab at the following dose levels: dostarlimab 500mg, belrestotug 100mg + dostarlimab 500mg (Dose A), belrestotug 400mg + dostarlimab 500mg (Dose B), and belrestotug 1000mg + dostarlimab 500mg (Dose C).
GALAXIES Lung-201臨時數據亮點
截至2024年6月7日的數據截止日，ESMO大會上呈報的臨時數據基於124名符合安全性和療效評估條件的患者（修改的意向治療≥5.6個月的隨訪）。患者服用dostarlimab或belrestotug + dostarlimab以下劑量：dostarlimab 500mg，belrestotug 100mg + dostarlimab 500mg（A劑量），belrestotug 400mg + dostarlimab 500mg（B劑量）和belrestotug 1000mg + dostarlimab 500mg（C劑量）。
Clinically meaningful improvement in the primary endpoint of ORR was observed consistently across each belrestotug + dostarlimab cohort (63.3% Dose A, 65.6% Dose B and 76.7% Dose C compared to 37.5% with dostarlimab alone). cORR, defined as complete or partial response confirmed by repeat imaging ≥4 weeks after response criteria first met, was roughly 60.0% for each dose compared to 28.1% cORR for dostarlimab alone.
Of the patients with evaluable paired ctDNA samples (baseline and week 7), median ctDNA reduction was 65% for dostarlimab monotherapy compared to 55% for Dose A, 94% for Dose B, and 97% for Dose C.
Belrestotug + dostarlimab led to an increase in immune-related adverse events compared to dostarlimab monotherapy, which were generally manageable. The safety profile of belrestotug in combination with dostarlimab has been broadly consistent with the known safety profile of combination therapy with checkpoint inhibitors. The most frequent treatment-related adverse events (≥15%) were skin and subcutaneous tissue disorders (50%) and endocrine disorders (26%), both commonly observed with immunotherapies.
在每個belrestotug + dostarlimab隊列中，原發終點ORR的臨床意義上的改善表現出一致性（Dose A爲63.3%，Dose b爲65.6%，Dose C爲76.7%，而dostarlimab獨服37.5%）。cORR（即初次滿足反應標準後≥4周的重複成像確認的完全或部分反應）分別爲每個劑量約60.0%，而dostarlimab單獨爲28.1%。
在可評估的配對ctDNA樣本患者（基線和第7周）中，與dostarlimab單獨療法相比，dostarlimab單獨治療的中位ctDNA減少65%，而Dose A爲55%，Dose b爲94%，Dose C爲97%。
Belrestotug + dostarlimab導致免疫相關不良事件的增加，而這些事件通常是可以控制的。Belrestotug與dostarlimab聯合治療的安全性概況與檢查點抑制劑聯合治療的已知安全性概況大體一致。最常見的治療相關不良事件(≥15%)爲皮膚和皮下組織障礙(50%)和內分泌障礙(26%)，這兩種障礙在免疫療法中常見。
Response measure in mITT |
Dostarlimab |
Dose A: |
Dose B: |
Dose C: |
Median follow-up, months (range) |
7.0 (0.2–16.6) |
8.5 (0.3–14.3) |
8.5 (0.4–16.2) |
6.7 (2.4–9.7) |
ORR,1,2% |
37.5% |
63.3% |
65.6% |
76.7% |
Complete response, n (%) |
0 |
0 |
0 |
0 |
Partial response, n (%) |
12 (37.5%) |
19 (63.3%) |
21 (65.6%) |
23 (76.7%) |
Stable disease, n (%) |
14 (43.8%) |
5 (16.7%) |
4 (12.5%) |
5 (16.7%) |
Progressive disease, n (%) |
2 (6.3%) |
4 (13.3%) |
3 (9.4%) |
2 (6.7%) |
Not evaluable/no assessment,3 n (%) |
4 (12.5%) |
2 (6.7%) |
4 (12.5%) |
0 |
Confirmed ORR,2 % |
28.1% |
60.0% |
59.4% |
63.3% |
mITT中的反應措施 |
Dostarlimab |
劑量A： |
劑量B： |
劑量C： |
中位隨訪時間，月（區間） |
7.0（0.2-16.6） |
8.5（0.3-14.3） |
8.5（0.4-16.2） |
6.7（2.4-9.7） |
ORR，1,2% |
37.5% |
63.3% |
65.6% |
76.7% |
完全反應，n (%) |
0 |
0 |
0 |
0 |
部分反應，n (%) |
12 (37.5%) |
19（63.3%） |
21（65.6%） |
23（76.7%） |
穩定疾病，n（%） |
14（43.8%） |
5（16.7%） |
4 (12.5%) |
5（16.7%） |
進展性疾病，n（%） |
2 (6.3%) |
4 (13.3%) |
3 (9.4%) |
2 (6.7%) |
無法評估/未評估，n（%） |
4 (12.5%) |
2 (6.7%) |
4 (12.5%) |
0 |
確定的整體反應,2 % |
28.1% |
60.0% |
59.4% |
63.3% |
1. unconfirmed ORR; 2. PD-L1 high (TPS ≥50%) was determined locally or centrally by DAKO 22C3 or VENTANA SP263 assay; 3. patients who only had "not evaluable" post baseline assessments, those who had a best response of "not evaluable" per RECIST 1.1 criteria, or those where no post-baseline tumor assessment was performed; CI, confidence interval
1. 未經證實的ORR；2. PD-L1高表達（TPS ≥ 50%）由DAKO 22C3或VENTANA SP263檢測在當地或中央確定；3. 僅進行了「不可評估」的基線評估，按照RECISt 1.1標準，最佳反應爲「不可評估」的患者，或者未進行基線後的腫瘤評估；CI，置信區間
Conference Call Details
The follow-up interim data from GALAXIES Lung-201 will be discussed during a conference call and webcast presentation on Monday, September 16th, 2024 at 8:00AM ET. To register for the webcast presentation, please visit the Events section on the Investors page of the iTeos website at investors.iteostherapeutics.com. A webcast replay may be accessed on the Investors section of the iTeos website.
電話會議詳情
GALAXIES Lung-201的後續中期數據將在2024年9月16萬億星期一上午8:00（東部標準時間）的電話會議和網絡直播中討論。請訪問iteos therapeutics的投資者網頁上的「活動」部分，註冊網絡直播。網絡直播回放可以在iteos therapeutics的投資者網頁上訪問。
Phase 2 GALAXIES Lung-201 Trial Design
The Phase 2 GALAXIES Lung-201 study is a randomized, open-label, global platform study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of novel immunotherapy combinations compared with immunotherapy monotherapy in participants with PD-L1 high (TPS ≥50%), previously untreated, unresectable, locally advanced or metastatic NSCLC. Arms and interventions in this study include: pembrolizumab (anti-PD-1) monotherapy, dostarlimab (anti-PD-1) monotherapy, belrestotug (anti-TIGIT) + dostarlimab doublet combination, and belrestotug + dostarlimab + nelistotug (anti-CD96) triplet combination.
GALAXIES肺癌-201的二期臨床試驗設計
GALAXIES肺部-201研究的2期是一項隨機、開放標籤、全球平台研究，評估與免疫治療單藥相比，新型免疫療法聯合應用的療效、安全性、藥代動力學和藥效動力學，用於PD-L1高表達（TPS≥50%）、以前未治療、不能手術切除的局部晚期或轉移非小細胞肺癌患者。該研究的干預組和干預措施包括：pembrolizumab（抗PD-1）單藥治療、dostarlimab（抗PD-1）單藥治療、belrestotug（抗TIGIT）+ dostarlimab雙藥組合和belrestotug + dostarlimab + nelistotug（抗CD96）三藥組合。
The primary endpoint of the study is investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include safety and additional efficacy measures such as progression free survival, overall survival, and duration of response.
該研究的主要終點是根據固體腫瘤療效評估標準（RECISt 1.1）的研究者評估的ORR。次要終點包括安全性和其他療效指標，如無進展生存期、總生存期和持續反應時間。
About iTeos Therapeutics, Inc.
iTeos Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients. iTeos Therapeutics leverages its deep understanding of tumor immunology and immunosuppressive pathways to design novel product candidates with the potential to restore the immune response against cancer. The Company's innovative pipeline includes three clinical-stage programs targeting novel, validated immunosuppressive pathways designed with optimized pharmacologic properties for improved clinical outcomes, including the TIGIT/CD226 axis and the adenosine pathway. iTeos Therapeutics is headquartered in Watertown, MA with a research center in Gosselies, Belgium.
關於iteos therapeutics, inc。
iteos therapeutics是一家臨床階段的生物製藥公司，致力於開拓新一代免疫腫瘤學治療藥物的發現和開發。iteos therapeutics利用其對腫瘤免疫學和免疫抑制通路的深刻理解，設計新型候選藥物，有潛力恢復對癌症的免疫反應。公司創新的產品線包括三個臨床階段項目，針對新穎的、經過驗證的免疫抑制通路，具有優化的藥理特性，以改善臨床結果，包括TIGIT/CD226通路和腺苷途徑。iteos therapeutics總部位於馬薩諸塞州的Watertown，在比利時的Gosselies設有研究中心。
About Belrestotug (EOS-448/ GSK4428859A)
Belrestotug is an Fc active human immunoglobulin G1, or IgG1, monoclonal antibody (mAb) targeting T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT), an important inhibitory receptor which contributes to the suppression of innate and adaptive immune responses against cancer. As an optimized high-affinity, potent anti-TIGIT mAb, belrestotug is designed to enhance the antitumor response through a multifaceted immune modulatory mechanism by engaging with TIGIT and FcγR, a key regulator of immune responses which induces cytokine release and antibody dependent cellular cytotoxicity (ADCC). The therapeutic candidate is progressing in multiple indications in collaboration with GSK.
關於Belrestotug（EOS-448/ GSK4428859A）
Belrestotug是一種Fc活性的人源免疫球蛋白G1（IgG1）單克隆抗體（mAb），靶向T細胞免疫球蛋白和免疫受體酪氨酸基抑制基序（TIGIT），TIGIT是一種重要的抑制性受體，有助於抑制對癌症的先天和獲得性免疫反應。作爲一個經優化的高親和力、有效的抗TIGIT mAb，Belrestotug通過與TIGIT和FcγR相互作用，增強抗腫瘤反應，通過多方面的免疫調節機制發揮作用，FcγR是免疫反應的關鍵調節因子，能夠誘導細胞因子的釋放和抗體依賴性細胞毒作用（ADCC）。該治療候選藥正在與GSK在多個適應症上進行合作推進。
譯文內容由第三人軟體翻譯。