Summit Therapeutics Inc. announced data from the primary analysis of the Phase III HARMONi-2 trial featuring the novel, potential first-in-class investigational bispecific antibody, ivonescimab

Summit Therapeutics Inc.宣布了III期HARMONi-2试验的初步分析数据，该试验具有新颖的，潜在的一流研究性双特异性抗体ivonescimab

The data was presented  as part of the Presidential Symposium at the International Association for the Study of Lung Cancer’s (IASLC) 2024 World Conference on Lung Cancer (WCLC 2024) in San Diego, California. The HARMONi-2 presentation, Phase II3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1-positive Advanced NSCLC: Primary Analysis of HARMONi-2, evaluated monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 TPS >1%).

这些数据是在加利福尼亚州圣地亚哥举行的国际肺癌研究协会（IASLC）2024年世界肺癌会议（WCLC 2024）上作为总统研讨会的一部分提交的。HARMONi-2介绍，Ivonescimab（AK112）与Pembrolizumab作为PD-L1阳性晚期NSCLC一线治疗的II3期研究：HARMONi-2的初步分析，评估了单药治疗Ivonescimab与单药治疗Pembrolizumab在局部晚期或转移性非小细胞肺癌（NSCLC）患者中的作用，其肿瘤具有阳性PD-L1表达（PD-L1 TPS>1%）。

HARMONi-2 is a single region, multicenter, double-blinded Phase III study conducted in China sponsored by our collaboration partner, Akeso, Inc. (Akeso, HKEX Code: 9926.HK), with data generated and analyzed by Akeso.

HARMONi-2是一项在中国进行的单区域、多中心、双盲III期研究，由我们的合作伙伴Akeso，Inc.（Akeso，香港交易所代码：9926。HK）赞助，数据由Akeso生成和分析。

. The trial results were presented by Professor Caicun Zhou, MD, PhD, Chief Physician and Director of the Department of Medical Oncology at Shanghai Pulmonary Hospital, Tongji University School of Medicine, and President-Elect of IASLC. Clinically Meaningful Efficacy; In the HARMONi-2 primary analysis, ivonescimab monotherapy demonstrated a statistically significant improvement in the trial’s primary endpoint, progression-free survival (PFS) by Independent Radiologic Review Committee (IRRC), when compared to monotherapy pembrolizumab, achieving a hazard ratio (HR) of 0.51 (95% CI: 0.38, 0.69; p<0.0001).

试验结果由同济大学医学院上海肺科医院主任医师兼肿瘤内科主任周彩村教授、医学博士、博士和IASLC当选主席介绍。临床上有意义的疗效；在HARMONi-2初步分析中，与单药治疗pembrolizumab相比，独立放射学审查委员会（IRRC）的ivonescimab单药治疗显示该试验的主要终点无进展生存期（PFS）有统计学显着改善，风险比（HR）为0.51（95%CI:0.38,0.69；p＜0.0001）。

A clinically meaningful benefit was demonstrated across clinical subgroups, including those with PD-L1 low expression (PD-L1 TPS 1-49%), PD-L1 high expression (PD-L1 TPS  greater than  50%), squamous and 1 non-squamous histologies, as well as other high-risk patients. Both the overall response rate (ORR) measured according to RECIST v1.1 criteria as well as the disease control rate (DCR) were higher in patients treated with ivonescimab compared to those treated with pembrolizumab. .

在临床亚组中证实了临床上有意义的益处，包括PD-L1低表达（PD-L1 TPS 1-49%），PD-L1高表达（PD-L1 TPS大于50%），鳞状和1个非鳞状组织学，以及其他高危患者。与使用pembrolizumab治疗的患者相比，使用ivonescimab治疗的患者根据RECIST v1.1标准测量的总体缓解率（ORR）以及疾病控制率（DCR）均更高。。

Manageable Safety Profile; Ivonescimab demonstrated an acceptable and manageable safety profile, which was consistent with previous studies. There were three patients (1.5%) who discontinued ivonescimab due to TRAEs compared to six patients (3.0%) who discontinued pembrolizumab due to TRAEs. There was one patient in the ivonescimab arm and two patients in the pembrolizumab arm who died as a result of TRAEs in this Phase III study.

可管理的安全概况；Ivonescimab表现出可接受且可管理的安全性，这与之前的研究一致。有3名患者（1.5%）因TRAEs停用了ivonescimab，而6名患者（3.0%）因TRAEs停用了pembrolizumab。在这项III期研究中，ivonescimab组有一名患者，pembrolizumab组有两名患者因TRAEs死亡。

The most frequent treatment-related adverse events (TRAEs) for ivonescimab treatment were proteinuria (Grade 3+: ivonescimab, 3.0%; pembrolizumab 0.0%), hypertension (Grade 3+: ivonescimab, 5.1%; pembrolizumab 0.5%), and various laboratory abnormalities, including AST increases, hypercholesterolemia, anemia, and bilirubin increases.

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Grade 3 or higher immune-related adverse events occurred in 7.1% of patients receiving ivonescimab and 8.0% of patients receiving pembrolizumab. Grade 3 or higher adverse events that were possibly VEGF-related in the ivonescimab monotherapy arm were 10.2% vs. 1.0% for pembrolizumab, all of which were classified as Grade 3.

接受ivonescimab治疗的患者中有7.1%发生3级或更高的免疫相关不良事件，接受pembrolizumab治疗的患者中有8.0%发生3级或更高的免疫相关不良事件。在ivonescimab单药治疗组中可能与VEGF相关的3级或更高级别不良事件为10.2%，而pembrolizumab为1.0%，所有这些都被归类为3级。

Of note, Grade 3 hemorrhage events were observed in two patients in the ivonescimab arm (both were of nonsquamous histology) compared to one patient in the pembrolizumab arm in this study..

值得注意的是，与本研究中pembrolizumab组的一名患者相比，ivonescimab组的两名患者（均为非鳞状组织学）观察到3级出血事件。。

This is a historic moment for ivonescimab, Team Summit, our partners at Akeso, and most importantly, we believe this is the beginning of a landscape shift for treatment options for patients living with cancer,” stated Robert W. Duggan, Chairman and Chief Executive Officer of Summit. “We are incredibly proud of our partnership with Akeso and their accomplishment with HARMONi-2..

这对于ivonescimab、Team Summit和我们在Akeso的合作伙伴来说是一个历史性的时刻，最重要的是，我们认为这是癌症患者治疗选择格局转变的开始，”Summit董事长兼首席执行官罗伯特·达根（Robert W.Duggan）表示。“我们为我们与Akeso的合作关系以及他们在HARMONi-2上取得的成就感到无比自豪。。

Based on the results of HARMONi-2, Summit announced its intention to initiate HARMONi-7 in early 2025. HARMONi-7 is currently planned as a multi-regional Phase III clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS > 50%). .

根据HARMONi-2的结果，峰会宣布打算在2025年初启动HARMONi-7。HARMONi-7目前计划作为一项多区域III期临床试验，将ivonescimab单药治疗与pembrolizumab单药治疗比较肿瘤具有高PD-L1表达（PD-L1 TPS>50%）的转移性NSCLC患者。。

“HARMONi-2 clearly demonstrates that ivonescimab has the potential to be the next generation in PD-1 directed immunotherapy, and potentially make a significant difference in the lives of patients with lung cancer and prospectively other tumors,” added Dr. Maky Zanganeh, Chief Executive Officer and President of Summit.

Summit首席执行官兼总裁Maky Zanganeh博士补充道：“HARMONi-2清楚地表明，ivonescimab有可能成为PD-1定向免疫治疗的下一代，并可能对肺癌患者和其他肿瘤患者的生活产生重大影响。”。

“We want to again congratulate Akeso for this incredible result and their work to advance the patient-friendly standards of care today and well into the future. We look forward to initiating HARMONi-7 and sharing additional details about our expanded clinical development plan in early 2025..

“我们要再次祝贺Akeso取得了这一令人难以置信的成果，以及他们在今天和未来为提高患者友好护理标准所做的工作。我们期待着在2025年初启动HARMONi-7，并分享有关我们扩大的临床发展计划的更多细节。。

Phase II Perioperative NSCLC; In addition to the HARMONi-2 data presentation, a second oral presentation featuring ivonescimab was presented by Xiaoliang Zhao, MD, Deputy Chief Physician, Department of Lung Cancer at Tianjin Medical University Cancer Institute & Hospital, and Visiting Scholar at the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, D.C.

II期围手术期NSCLC；。

The presentation was entitled, A Phase II Study of Perioperative Ivonescimab Alone or Combined with Chemotherapy in Resectable Non-Small Cell Lung Cancer, presenting the results from AK112-205, a single-region (China), multi-center, open-label Phase II study of patients with Stage II or III resectable NSCLC.

该报告的标题为围手术期Ivonescimab单独或联合化疗治疗可切除非小细胞肺癌的II期研究，介绍了AK112-205的结果，AK112-205是一项单区域（中国），多中心，开放标签的II期研究II期或III期可切除非小细胞肺癌患者。

The study is designed to assess patients receiving either ivonescimab monotherapy or ivonescimab plus chemotherapy prior to surgical resection and then ivonescimab monotherapy after surgery. Due to the maturity of the data and the timing of the data cutoff, the results were limited to the neo-adjuvant, or pre-surgery, portion of the clinical trial.

该研究旨在评估在手术切除前接受ivonescimab单药治疗或ivonescimab加化疗的患者，然后在手术后接受ivonescimab单药治疗。。

At the time of data cutoff, 49 patients had been enrolled into the ivonescimab plus chemotherapy arm in the neo-adjuvant setting; of these 49 patients, 39 went on to complete surgery. .

在数据截止时，49名患者已被纳入新辅助治疗中的ivonescimab加化疗组；在这49名患者中，39名继续完成手术。。

Results; Of the 39 patients who received ivonescimab plus chemotherapy in the neo-adjuvant stage and completed surgery, 71.8% of patients experienced a major pathological response (MPR) and 43.6% of patients experienced a pathological complete response (pCR). In the 49 patients enrolled in this cohort, median event-free survival (EFS) was not yet reached after 8.9 months of median follow-up time; the 12-month EFS rate was 80.3% (95% CI: 59.6, 91.1).

结果；在新辅助阶段接受ivonescimab加化疗并完成手术的39例患者中，71.8%的患者经历了主要病理反应（MPR），43.6%的患者经历了病理完全反应（pCR）。在该队列的49名患者中，中位随访时间为8.9个月后，中位无事件生存期（EFS）尚未达到；12个月EFS率为80.3%（95%CI:59.6,91.1）。

These results are encouraging compared to the historical data that has been observed in global pivotal studies in a similar setting. The safety profile was manageable: of the 49 patients who received ivonescimab plus chemotherapy in the neo-adjuvant setting, Grade 3 or higher adverse events were observed in 32.7% of patients; there was one patient who experienced a treatment-related serious adverse event.

与类似环境下全球关键研究中观察到的历史数据相比，这些结果令人鼓舞。安全性是可控的：在新辅助治疗中接受ivonescimab加化疗的49例患者中，32.7%的患者出现3级或更高级别的不良事件；有一名患者经历了与治疗相关的严重不良事件。

There were no TRAEs leading to delayed or cancelled surgery or that led to the death of a patient..

没有TRAEs导致手术延迟或取消或导致患者死亡。。

Additional Phase II Data to be Presented at ESMO 2024; Beyond the data recently featured at WCLC 2024, Phase II data featuring ivonescimab will be presented at the European Society of Medical Oncology (ESMO) Congress 2024. ESMO 2024 will take place in Barcelona, Spain, from September 13 – 17, 2024.  These presentations, which will feature data from studies sponsored by Akeso including first-line treatment for triple-negative advanced breast cancer (TNBC), first-line treatment for advanced head and neck squamous cell carcinoma (HNSCC), and first-line treatment of advanced colorectal cancer (CRC)..

将在ESMO 2024上提交的其他二期数据；除了最近在WCLC 2024上发布的数据外，以ivonescimab为特征的第二阶段数据将在2024年欧洲医学肿瘤学会（ESMO）大会上发布。2024年ESMO将于2024年9月13日至17日在西班牙巴塞罗那举行。这些演讲将展示由Akeso赞助的研究数据，包括三阴性晚期乳腺癌（TNBC）的一线治疗，晚期头颈部鳞状细胞癌（HNSCC）的一线治疗以及晚期结直肠癌（CRC）的一线治疗。。

Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3, with a plan to initiate HARMONi-7 in early 2025. HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic nonsquamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib).

Summit已开始在非小细胞肺癌（NSCLC）中开发ivonescimab的临床开发，并于2023年开始参加两项多区域III期临床试验HARMONi和HARMONi-3，计划于2025年初启动HARMONi-7。HARMONi是一项III期临床试验，旨在评估ivonescimab联合化疗与安慰剂加化疗相比，对EGFR突变，局部晚期或转移性非鳞癌NSCLC患者进行治疗后，用第三代EGFR TKI（例如osimertinib）治疗进展。

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC. HARMONi-7 is a planned Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 TPS > 50%).

HARMONi-3是一项III期临床试验，旨在评估ivonescimab联合化疗与pembrolizumab联合化疗治疗一线转移性鳞状NSCLC患者的疗效。HARMONi-7是一项计划进行的III期临床试验，旨在评估与pembrolizumab单药治疗相比，ivonescimab单药治疗具有高PD-L1表达（PD-L1 TPS>50%）的一线转移性NSCLC患者。

In addition, Akeso has recently had positive read-outs in two single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC, HARMONi-A and HARMONi-2..

此外，Akeso最近在两个单区域（中国）的非小细胞肺癌（HARMONi-A和HARMONi-2）中进行了ivonescimab的随机III期临床试验，结果显示阳性。。

Condition: Non Small Cell Lung Cancer

病情：非小细胞肺癌

Type: drug

类型：药物