百靈佳殷格翰 Zongertinib 在先前已接受過治療的 HER2 基因突變肺癌患者中顯示出令人鼓舞的療效和耐受性

百靈佳殷格翰公布了 Beamion LUNG-1 第 Ib 期臨床試驗的試驗族群 1(cohort 1)的初步數據分析的正面結果。在此項針對先前已接受過治療的HER2 基因突變晚期非小細胞肺癌（NSCLC）患者，使用 zongertinib（BI 1810631）進行療效評估的臨床試驗中，zongertinib 在試驗族群1中顯示出有意義的客觀反應率，且耐受性普遍良好。此結果在 2024 年國際肺癌研究協會（IASLC）世界肺癌大會（WCLC）的主席研討會及 2024年官方的 WCLC 新聞中發表。

截至 2024 年 5 月，共有 132 名患者接受了每天 120 毫克或 240 毫克的 Zongertinib 治療(n=75/n=57)。經由盲性獨立中央審查委員會(Blinded independent central review, BICR)評估，發現試驗族群1(120 毫克；n=75)數據達到了主要療效指標，經確認的客觀反應率(ORR)達 66.7%，97.5% CI (53.8–77.5)，(p<0.0001)。根據試驗主持人的評估，在所有劑量組的94%患者中觀察到了不同程度的腫瘤縮小情形。臨床試驗設計包括劑量擴增，以期找到該患者群體的最佳劑量。患者被隨機分配到 120 毫克（n=58）或 240 毫克（n=55）組別。經過試驗期中無效性分析後，選擇 120 毫克作為試驗族群1的治療劑量進一步評估，並追加招募 17 名患者。在患者以1:1比例隨機分配的部分試驗中，zongertinib 在每天 120 毫克治療的患者中達72.4% 的反應率，而在每天 240 毫克治療的患者中則達 78.2% 的反應率，疾病控制率（DCR）分別為 95% 和 100%。

第 Ib 期臨床試驗的試驗族群 1數據同時也顯示了 Zongertinib 的初步腦部抗腫瘤活性。由盲性中央獨立評估委員會 （BICR）依據 RANO-BM（腫瘤腦轉移療效評估標準）評估，33%（120 毫克；n=27）和 40%（240 毫克；n=25）的無症狀腦轉移患者達到確認的客觀反應，且疾病控制率（DCR）分別為 74% 和 92%。中樞神經系統是非小細胞肺癌常見的轉移部位，與預後不良和生活質量下降相關。具有 HER2基因突變的非小細胞肺癌患者在診斷時，有多達 30% 患者已發生腦轉移。

該試驗的主要研究主持人，德克薩斯大學 MD Anderson Cancer Center的 John Heymach 博士（MD，PhD）表示 “這些新數據可能為未來治療具有 HER2 突變的非小細胞肺癌患者帶來好消息”。“雖然這些基因突變很罕見，但仍可能是部分非小細胞肺癌病例中的關鍵驅動因素，且目前的治療選擇非常有限。這類癌症患者通常面臨不良預後，約 50% 的患者對目前一線治療有反應，且僅 20% 的患者對二線治療有反應。”

Zongertinib 是一種正在開發中的口服 HER2 酪氨酸激酶抑制劑（TKI），正在研究其在具有 HER2 突變的晚期非小細胞肺癌（NSCLC）患者中的治療療效。Zongertinib 的設計目的是避免影響野生型表皮生長因子受體 EGFR，從而減少相關的毒性。Beamion LUNG-2 是一項全球正在招募患者的第III 期臨床試驗，針對具有 HER2 突變的晚期 NSCLC 患者，評估 Zongertinib相較於標準治療的第一線治療效果。

百靈佳殷格翰董事會成員、創新單位負責人 Paola Casarosa 表示：“Zongertinib 的療效和耐受性特徵，有潛力成為未來 HER2 突變肺癌患者治療方案的選擇之一。Zongertinib 是我們在新療法發現和開發中科學方法的完美例子。百靈佳殷格翰致力於為癌症患者提供突破性療法，我們期待推進 zongertinib 臨床試驗計畫。

Zongertinib 在 120 毫克和 240 毫克劑量下普遍耐受性良好，無治療相關死亡，因副作用發生導致須減少劑量或停止用藥的比例低（分別為11%及3%）。未觀察到新的安全信號或治療相關的間質性肺病（ILD），接受 zongertinib 治療的患者中，17%（120 毫克）和 19%（240 毫克）出現了 3 級或以上的治療相關不良事件（TRAEs）。最常見的 TRAEs 是 1 級或 2 級腹瀉（分別為 43% 和 11%）和 1 級或 2 級皮疹（分別為 19% 和 8%）。

該試驗資料仍在持續分析中，且在此次數據截止時，三分之二的受試患者仍在接受治療，無疾病惡化存活期（PFS）和反應持續時間（DoR）等試驗數據將會在即將舉行的醫學年會上釋出。

關於非小細胞肺癌（NSCLC）

肺癌奪走的生命比任何其他癌症都多，預計到 2040 年，全球肺癌病例將增加到超過 300 萬例。NSCLC  是最常見的肺癌類型。該病症通常在晚期診斷，診斷後五年內存活的患者不到三成。患有晚期 NSCLC 的人可能會在日常生活中經歷身體、心理和情感上的負面影響。對於患有晚期 NSCLC 的人來說，仍然有很高的未滿足治療需求。多達 4%  的肺癌是由 HER2 突變（或基因改變）引起的。HER2  突變可導致過度表達和過度激活，進而導致細胞不受控制地生長、抑制細胞死亡並促進腫瘤生長和擴散。

關於百靈佳殷格翰 Boehringer Ingelheim

百靈佳殷格翰是一家全球領先的生物製藥企業，包含人用處方用藥與動物保健兩大業務。作為產業中研發投入最高的公司之一，百靈佳殷格翰致力於研究突破性療法，解決巨大而未被滿足的醫療需求。百靈佳殷格翰自1885年成立以來一直是一家獨立的家族企業，始終著眼長遠發展，並將永續發展嵌入價值鏈。公司在全球有超過5.3萬名員工，服務逾130個市場，致力於打造一個更健康、更永續、更公平的未來。更多詳情，請訪問：www.boehringer-ingelheim.com/tw

「台灣百靈佳殷格翰股份有限公司」與「台灣百靈佳殷格翰動物事業股份有限公司」是百靈佳殷格翰在台子公司，成立於1975年，迄今已逾49年，目前在台灣北、中、南共設有3個辦公室，員工近350人。人類處方用藥及動物保健是公司的核心業務，人類處方用藥持續在呼吸道疾病、癌症、糖尿病、心血管疾病、中風、巴金森病、纖維化疾病等領域幫助更多病患；動物保健方面，我們持續在內外寄生蟲預防、心臟疾病、慢性腎病與疼痛治療上協助伴侶動物與其照顧者，更也在許多疾病上協助經濟動物產業的畜場主人，如豬隻環狀病毒及藍耳病、家禽馬立克病及新城雞病…等。
 

Boehringer’s zongertinib shows encouraging efficacy and tolerability profile in previously treated HER2 mutated lung cancer patients

• Beamion LUNG-1, Phase Ib met its primary endpoint, demonstrating a meaningful objective response rate (ORR) of 66.7%, as assessed by blinded independent central review (BICR)[i]
• Preliminary activity in patients with brain metastases were also observed, with an intracranial response of 33% and 74% disease control rate (DCR) 
• Zongertinib was generally well tolerated, with mostly mild and manageable treatment related adverse events (TRAE) and low discontinuation rate due to toxicity (3%)

• With two thirds of patients still on treatment at data cut-off, more mature data including progression-free survival (PFS), and duration of response (DoR) will be reported later in the year

   

Boehringer Ingelheim reports positive results from a Phase Ib primary analysis of Cohort 1 of the Beamion LUNG-1 trial evaluating zongertinib (BI 1810631) in pre-treated patients with advanced non-small cell lung cancer (NSCLC) with activating HER2 mutations. Zongertinib demonstrated a meaningful objective response rate and was generally well tolerated in the Cohort 1 setting. The results were presented in a Presidential Symposium at the IASLC 2024 World Conference on Lung Cancer (WCLC) and are included in the official 2024 WCLC Press Program. 

As of May 2024, 132 patients have been treated with 120 mg / 240 mg of zongertinib once a day (n=75/n=57).  With a confirmed objective response rate (ORR) of 66.7%, 97.5% CI (53.8–77.5), (p<0.0001) as assessed by blinded independent central review (BICR), the primary endpoint was met for Cohort 1 (120 mg; n=75). Tumor shrinkage of any magnitude was observed in 94% of all patients across doses, per investigator assessment. The trial design includes a dose expansion that was carried out to find the optimal dose of zongertinib for this patient population. Patients were randomized 1:1 to either the 120 mg (n=58) or the 240 mg (n=55) group. After an interim futility analysis, 120 mg was selected as the dose to be evaluated further in Cohort 1, and 17 additional patients were enrolled. In the part of the trial where patients were randomized 1:1, zongertinib showed a response rate of 72.4% in patients treated with 120 mg daily, and 78.2% in patients treated with 240 mg daily as well as disease control rates (DCRs) of 95% and 100% respectively. 

Phase Ib, Cohort 1 data also shows preliminary brain activity with zongertinib. 33% (120 mg; n=27) and 40% (240 mg; n =25) of patients with asymptomatic brain metastases achieved confirmed objective response, with a DCR of 74% and 92% respectively, as per RANO-BM (recommendations for standardized tumor response and progression assessment) by BICR. The central nervous system is a common site of metastasis in NSCLC and is associated with poor prognosis and quality of life.¹ Brain metastases are present in up to 30% of patients with NSCLC with activating HER2 mutations at diagnosis.² 

"These new data could represent positive news in the future treatment of non-small cell lung cancer patients with activating HER2 mutations," said the trial’s principal investigator, Dr. John Heymach, MD, PhD, The University of Texas MD Anderson Cancer Center. "While these mutations are rare, they are critical drivers in a subset of non-small cell lung cancer cases, and current treatment options are severely limited. Patients with this type of cancer typically face a poor prognosis, with approximately 50% responding to first-line treatment and only 20% responding to second-line therapy.”^4,5,6,7

Zongertinib is an investigational oral HER2 tyrosine kinase inhibitor (TKI) in development being investigated in patients with advanced NSCLC with activating HER2 mutations.  Zongertinib was designed to spare wild-type EGFR thereby mitigating associated toxicities. Beamion LUNG-2, a global Phase III trial evaluating zongertinib compared to standard of care as first-line treatment in patients with advanced NSCLC with activating HER2 mutations is currently enrolling.

Paola Casarosa, Board of Managing Directors, Head of Innovation Unit at Boehringer Ingelheim, said: “Zongertinib’s efficacy and tolerability profile has the potential to become part of the future treatment landscape for patients with HER2 mutated lung tumors. Zongertinib is a perfect example of our approach to science in the discovery and development of novel treatments. Boehringer is committed to providing breakthrough therapies for cancer patients, and we look forward to advancing the zongertinib clinical program.”

Zongertinib was generally well tolerated for 120 mg and 240 mg, with no deaths attributed to treatment and a low incidence of adverse events leading to dose reductions (11%) and discontinuation (3%). No new safety signals or treatment-related interstitial lung diseases (ILD) were observed, and Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 17% (120 mg) and 19% (240 mg) of patients treated with zongertinib. The most common TRAEs were Grade 1 or 2 diarrhea (43% and 11% respectively), Grade 1 or 2 rash (19% and 8% respectively).

Data are still maturing and with two thirds of responding patients still on treatment at data cut-off, progression-free survival (PFS) and duration of response (DoR) data will be reported at an upcoming conference.
 

About non-small cell lung cancer (NSCLC) 

Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.⁸  NSCLC is the most common type of lung cancer.⁹ The condition is often diagnosed at a late stage,¹⁰  and fewer than 3 in 10 patients are alive five years after diagnosis.¹¹  People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations). ¹²  Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread. ¹³

 

About zongertinib 

Zongertinib (also known as BI 1810631) is an investigational oral HER2-specific tyrosine kinase inhibitor (TKI) that is being developed as a potential treatment for HER2 mutated non-small cell lung cancer (NSCLC). Zongertinib was granted FDA Fast Track Designation in 2023, then in 2024 it was granted Breakthrough Therapy Designation by the U.S. FDA and China CDE for the treatment of adult patients with advanced NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. HER2 is a member of the ErbB family of receptor tyrosine kinases (enzymes that act like chemical messengers).¹³ A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy or with KRAS-targeted drugs. ¹⁴
 

About the Beamion clinical trial program 

Beamion LUNG-1 (NCT04886804): An open-label, Phase I dose escalation trial, with dose confirmation and expansion, of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 mutations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a phase 3, open label, randomized, active-controlled study that will enroll 270 patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 tyrosine kinase domain mutations to evaluate Zongertinib compared with standard of care. 

About Boehringer Ingelheim in Oncology 

We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim’s generational commitment to driving scientific innovation is reflected by the company’s robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer’s ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. 

About Boehringer Ingelheim

Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow.