HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences, Inc. (NYSE:RCUS) today announced promising overall survival data from ARC-8, a Phase 1b study that is being co-developed with Gilead Sciences. ARC-8 is the study of quemliclustat, an investigational small molecule CD73 inhibitor, plus chemotherapy with or without zimberelimab, an investigational anti-PD-1 antibody, in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).

加利福尼亚州海沃德（商业新闻短讯）--Arcus Biosciences，Inc.（纽约证券交易所：RCUS）今天宣布了ARC-8的总体生存数据，这是一项与吉利德科学公司（Gilead Sciences）共同开发的1b期研究。ARC-8是对先前未经治疗的转移性胰腺导管腺癌（mPDAC）患者进行的研究性小分子CD73抑制剂quemliclustat加上有或没有zimberelimab（一种研究性抗PD-1抗体）的化疗的研究。

The results will be presented during the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI)..

研究结果将在2024年美国临床肿瘤学会胃肠道癌症研讨会（ASCO GI）上发表。。

“A quemliclustat-based regimen appears to meaningfully prolong survival compared to what we typically observe in patients with mPDAC who receive chemotherapy alone, the standard of care for more than 30 years,” said Zev A. Wainberg, MD, MSc, Co-Director of the GI Oncology Program at University of California Los Angeles and a principal investigator of the ARC-8 trial.

加州大学洛杉矶分校胃肠肿瘤项目联合主任兼ARC-8试验首席研究员Zev A.Wainberg医学博士、理学硕士说：“与我们通常观察到的仅接受化疗的mPDAC患者相比，基于quemliclustat的方案似乎可以显着延长生存期。”。

“CD73 is highly expressed on pancreatic cancer cells, and I am encouraged to see early evidence that inhibiting CD73 with a small molecule has the potential to improve outcomes for people with mPDAC, without an observed clinically meaningful increase in toxicity, when combined with standard of care chemotherapy relative to historical data for chemotherapy alone.”.

“CD73在胰腺癌细胞上高度表达，我很高兴看到早期证据表明，用小分子抑制CD73有可能改善mPDAC患者的预后，而与标准化疗相结合时，没有观察到临床上有意义的毒性增加相对于单独化疗的历史数据。”。

The results to be presented include data from all patients (n=122) with treatment-naïve (first-line) mPDAC who received 100mg of quemliclustat plus chemotherapy with or without zimberelimab in the dose-escalation, dose-expansion and randomization cohorts of ARC-8. The data cutoff was June 19, 2023. Median overall survival (mOS) data for both quemliclustat-based regimens were numerically greater than historical benchmark data for chemotherapy alone, which has shown a mOS of approximately nine months..

将要呈现的结果包括来自所有未接受治疗（一线）mPDAC的患者（n=122）的数据，这些患者在剂量递增，剂量扩展和随机分组ARC-8中接受100mg quemliclustat加化疗，有或没有zimberilimab。数据截止日期为2023年6月19日。基于quemliclustat的两种方案的中位总生存期（mOS）数据在数值上均大于单独化疗的历史基准数据，后者显示mOS约为9个月。。

An analysis was performed by the Medidata AI team, part of Medidata, a Dassault Systèmes company, whereby they constructed a Synthetic Control Arm of patients who were treated with gemcitabine/nab-paclitaxel in Phase 2 and 3 clinical studies in the first-line metastatic pancreatic cancer setting, on a post-hoc basis.

Medidata AI团队（一家达索系统公司Medidata的一部分）进行了一项分析，他们在一线转移性胰腺癌患者的2期和3期临床研究中构建了一个合成对照组，这些患者接受了吉西他滨/纳布紫杉醇治疗。

Patients from these studies were matched 1:1 to the pool of 122 patients treated with the 100 mg quemliclustat-based regimens in ARC-8, based on demographics and key baseline characteristics such as ECOG performance status, liver metastasis, and history of prior surgery. The matched SCA was constructed based on a pre-specified analysis plan before OS data were unblinded and analyzed by the Medidata AI team.

根据人口统计学和关键基线特征，如ECOG表现状态，肝转移和既往手术史，这些研究的患者与ARC-8中使用100 mg基于quemliclustat的方案治疗的122名患者的比例为1:1。匹配的SCA是根据预先指定的分析计划构建的，然后由Medidata AI团队解开OS数据并进行分析。

The analysis showed that the patients in ARC-8 lived longer than patients from the matched control arm. Specifically, these results showed that patients in ARC-8 experienced a:.

分析表明，ARC-8患者比匹配对照组患者寿命更长。具体而言，这些结果表明，ARC-8患者经历了：。

37% reduction in the risk of death, HR=0.63 (CI: 0.47 – 0.85, p=0.0030) and a

死亡风险降低37%，HR=0.63（CI:0.47-0.85，p=0.0030），a

5.9-month increase in mOS (15.7 vs 9.8 months) relative to the matched control arm.

相对于匹配的对照组，mOS增加了5.9个月（15.7比9.8个月）。

The efficacy data for the pooled dose-escalation, dose-expansion and randomized arms, as well as the data from the SCA, are summarized below:

汇总剂量递增、剂量扩展和随机分组的疗效数据以及SCA的数据总结如下：

A2: Q+G/nP*

A2:Q+G/nP*

(n=29)

（n=29）

A1: QZ+G/nP**

A1:QZ+G/nP**

(n=61)

（n=61）

Pooled Q100

合并Q100

QZ+G/nP***

QZ+G/nP***

(n=93)

（n=93）

All Pooled Q100

所有合并Q100

Q±Z+G/nP

Q±Z+G/nP

(n=122)****

（n=122）****

Post-hoc

事后

Synthetic

合成

Control Arm

控制臂

(n=122)*****

（n=122）*****

Median OS, months (95% CI)

中位OS，月（95%置信区间）

19.4 (12.1, 23.0)

19.4 (12.1, 23.0)

14.6 (10.6, 21.5)

14.6 (10.6, 21.5)

13.9 (11.1, 18.7)

13.9 (11.1, 18.7)

15.7 (12.4, 20.9)

15.7 (12.4, 20.9)

9.8 (7.8, 11.4)

9.8 (7.8, 11.4)

Hazard Ratio

危险比

(95% CI)

（95%置信区间）

HR=0.63 (0.47 – 0.85)

HR=0.63（0.47-0.85）

p=0.0030)

p=0.0030）

12-month OS

12个月操作系统

72.3%

72.3%

60.9%

60.9%

59.6%

59.6%

62.7%

62.7%

41.1%

41.1%

Median PFS, months (95% CI)

中位PFS，月（95%置信区间）

8.8 (6.4, 12.6)

8.8 (6.4, 12.6)

4.9 (3.7, 6.0)

4.9 (3.7, 6.0)

5.4 (4.9, 7.3)

5.4 (4.9, 7.3)

6.3 (5.4, 7.7)

6.3 (5.4, 7.7)

5.5 (4.4, 6.6)

5.5 (4.4, 6.6)

Hazard Ratio

危险比

(95% CI)

（95%置信区间）

HR=0.78 (0.58‑1.05)

小时=0.78（0.58-1.05）

p=0.1102

p=0.1102

ORR, % (95% CI)

ORR，%（95%CI）

41 (24, 61)

41 (24, 61)

34 (23, 48)

34 (23, 48)

38 (28, 48)

38 (28, 48)

39 (29.9, 47.8)

39 (29.9, 47.8)

41 (32.2, 50.3)

41 (32.2, 50.3)

Q, Quemliclustat; Z, Zimberelimab; G/nP, gemcitabine / nab‑paclitaxel; CI, confidence interval

Q、 Quemliclustat；Z、 Zimberelimab；G/nP、吉西他滨/nab紫杉醇；CI，置信区间

*Cohort A2 – patients randomized to Q+G/nP in the dose-expansion phase.

*队列A2–在剂量扩展阶段随机分配到Q+G/nP的患者。

**Cohort A1 – patients randomized to QZ+G/nP in the dose-expansion phase.

**队列A1–在剂量扩展阶段随机分配到QZ+G/nP的患者。

***Pooled Q100 QZ+G/nP – treatment-naïve patients receiving 100 mg of quemliclustat plus zimberelimab and G/nP across dose- escalation, expansion and randomization phases.

***合并Q100 QZ+G/nP治疗初治患者在剂量递增，扩大和随机化阶段接受100 mg quemliclustat加zimberimab和G/nP。

****All Pooled – treatment-naïve patients receiving 100 mg of quemliclustat with or without zimberelimab across dose- escalation, dose-expansion and randomization phases.

****所有未接受治疗的患者在剂量递增，剂量扩大和随机化阶段接受100 mg quemliclustat，有或没有zimberilimab。

*****Synthetic Control Arm (Historical Control) – Historical clinical trial data from patients treated with G/nP, balanced to the baseline characteristics of ARC-8 participants. The Synthetic Control Arm data were compared to the All Pooled group.

*****合成对照组（历史对照）-来自接受G/nP治疗的患者的历史临床试验数据，与ARC-8参与者的基线特征相平衡。将合成对照组数据与所有合并组进行比较。

No new safety signals were observed in the study. The most common adverse events (Grade 3 or higher) were neutropenia (37.9%, 34.4% and 38.7%) and anemia (27.6%, 26.2% and 23.7%), respectively, for cohorts A2, A1 and Pooled Q100 QZ+G/nP. Five deaths were reported, and none were considered by the study investigators to be related to quemliclustat or zimberelimab..

在研究中没有观察到新的安全信号。对于队列A2，A1和合并Q100 QZ+G/nP，最常见的不良事件（3级或更高）分别是中性粒细胞减少（37.9%，34.4%和38.7%）和贫血（27.6%，26.2%和23.7%）。据报道有5人死亡，研究人员认为没有人与quemliclustat或zimberelimab有关。。

Quemliclustat and zimberelimab are investigational molecules. Arcus and Gilead have not received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of pancreatic cancer have not been established.

Quemliclustat和zimberelimab是研究分子。Arcus和Gilead尚未获得任何监管机构的全球任何使用批准，其治疗胰腺癌的安全性和有效性尚未确定。

About Quemliclustat

关于Quemliclustat

Quemliclustat is an investigational, potent and selective small molecule CD73 inhibitor. CD73 is the primary enzymatic producer of immunosuppressive adenosine in the tumor microenvironment, and high CD73 expression is associated with significantly poorer prognosis in several tumor types. Quemliclustat has been shown to block the production of adenosine.

Quemliclustat是一种研究性，有效和选择性的小分子CD73抑制剂。CD73是肿瘤微环境中免疫抑制腺苷的主要酶促产生者，高CD73表达与几种肿瘤类型的预后显着较差有关。Quemliclustat已被证明可以阻断腺苷的产生。

Once the immunosuppressive effects of adenosine are removed, activation of antitumor immune cells may be restored, resulting in cancer cell death..

一旦腺苷的免疫抑制作用被消除，抗肿瘤免疫细胞的激活可能会恢复，导致癌细胞死亡。。

Arcus and Gilead are currently evaluating quemliclustat in combination with other molecules within the collaboration portfolio with chemotherapy, including Phase 2 studies in lung and upper gastrointestinal cancers.

Arcus和Gilead目前正在评估quemliclustat与化疗合作组合中的其他分子的组合，包括肺癌和上消化道癌的2期研究。

About the ARC-8 Trial

关于ARC-8试验

The ARC-8 trial is a Phase 1b, open-label, dose-escalation and dose-expansion platform study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of combinations of the small molecule CD73 inhibitor quemliclustat, anti-PD-1 antibody zimberelimab and chemotherapy (gemcitabine / nab‑paclitaxel, or G/nP) in participants with advanced pancreatic cancer..

ARC-8试验是一项1b期，开放标签，剂量递增和剂量扩展平台研究，旨在评估小分子CD73抑制剂quemliclustat，抗PD-1抗体zimberilimab和化疗（吉西他滨/纳布紫杉醇或G/nP）联合应用于晚期胰腺癌患者的安全性，耐受性，药代动力学，药效学和临床活性。。

After the dose-escalation phase, quemliclustat 100 mg was selected as the dose for expansion. Patients were treated with quemliclustat 100 mg every two weeks plus standard doses of chemotherapy and zimberelimab (240 mg IV every two weeks) in Cohort A (treatment-naïve mPDAC) of the dose-expansion phase and then randomized 2:1 to receive quemliclustat plus zimberelimab and chemotherapy (Cohort A1) or quemliclustat plus chemotherapy (Cohort A2).

剂量递增阶段后，选择quemliclustat 100 mg作为扩大剂量。在剂量扩展阶段的队列A（未经治疗的mPDAC）中，患者每两周接受一次100 mg的奎米司他加标准剂量的化疗和zimberilimab（每两周240 mg IV），然后以2:1的比例随机接受quemliclustat加zimberimab和化疗（队列A1）或quemliclustat加化疗（队列A2）。

Pooled analyses were conducted to reflect: 1) all treatment-naïve patients who received quemliclustat 100 mg plus zimberelimab and chemotherapy from dose-escalation and dose-expansion phases and 2) all treatment-naïve patients receiving 100 mg of quemliclustat with or without zimberelimab across dose-expansion and escalation phases.

进行汇总分析以反映：1）从剂量递增和剂量扩展阶段接受喹莫利司他100 mg加齐姆利单抗和化疗的所有未接受治疗的患者，以及2）在剂量扩展和升级阶段接受或不接受齐姆利单抗100 mg喹莫利司他的所有未接受治疗的患者。

Endpoints included safety, overall response rate, median overall survival and progression‑free survival. More information about ARC-8 is available at: https://www.clinicaltrials.gov/study/NCT04104672..

终点包括安全性，总有效率，中位总生存期和无进展生存期。有关ARC-8的更多信息，请访问：https://www.clinicaltrials.gov/study/NCT04104672..

Additionally, an analysis comparing the All Pooled cohort to a Synthetic Control Arm (SCA) was conducted to address the differences in patient characteristics in the study cohorts, particularly in relation to decreased presence of liver metastases at baseline in cohort A2. The SCA consisted of historical clinical trial data from patients treated with G/nP, with baseline characteristics matched to those of ARC-8 participants..

此外，进行了一项将所有合并队列与合成对照组（SCA）进行比较的分析，以解决研究队列中患者特征的差异，特别是与队列A2基线时肝转移的存在减少有关。SCA由接受G/nP治疗的患者的历史临床试验数据组成，其基线特征与ARC-8参与者的基线特征相匹配。。

About Pancreatic Cancer

关于胰腺癌

Pancreatic cancer occurs in the pancreas, an organ located behind the stomach that helps with digestion and controlling blood sugar. Pancreatic cancer is one of the most aggressive cancers, with a dismal prognosis. Approximately 50% of patients with PDAC are diagnosed in the metastatic setting, which is associated with a 5-year survival rate of only 3%.

胰腺癌发生在胰腺中，胰腺是位于胃后面的一个器官，有助于消化和控制血糖。胰腺癌是最具侵袭性的癌症之一，预后不佳。大约50%的PDAC患者被诊断为转移性疾病，其5年生存率仅为3%。

Over 80% of pancreatic cancers are diagnosed at a late stage. The majority (over 90%) of pancreatic cancers are adenocarcinomas, a type of cancer that forms in tissues that line certain internal organs and release fluids like those that help with digestion. There have been limited advancements for treating pancreatic cancer, and chemotherapy has been the standard of care for more than 30 years..

超过80%的胰腺癌被诊断为晚期。大多数（超过90%）的胰腺癌是腺癌，这是一种在某些内部器官排列的组织中形成的癌症，并释放出有助于消化的液体。治疗胰腺癌的进展有限，化疗已成为标准治疗30多年。。

About Arcus Biosciences

关于Arcus Biosciences

Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination medicines for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- and best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer.

Arcus Biosciences是一家临床阶段的全球生物制药公司，为癌症患者开发分化分子和联合药物。与世界各地的行业合作者、患者和医生合作，Arcus正在加速开发一流和一流的药物，以对抗特征明确的生物靶标和途径，并研究新颖的生物学驱动的组合，这些组合有可能帮助癌症患者活得更长。

Founded in 2015, the company has expedited the development of multiple investigational medicines into clinical studies, including new combination approaches that target TIGIT, PD-1, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information about Arcus Biosciences’ clinical and pre-clinical programs, please visit www.arcusbio.com..

该公司成立于2015年，加快了多种研究药物进入临床研究的发展，包括针对TIGIT，PD-1，腺苷轴（CD73和双A2a/A2b受体），HIF-2a，CD39和AXL的新组合方法。有关Arcus Biosciences临床和临床前项目的更多信息，请访问www.arcusbio.com。。

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the statements in Dr.

本新闻稿包含前瞻性声明。本文所包含的所有关于未来发生的事件或结果的陈述均为前瞻性陈述，反映了管理层根据1995年《私人证券诉讼改革法案》的安全港条款所做出的当前信念和期望，包括但不限于Dr。

Wainberg’s quote and statements regarding: the timing and scope of analyses, data disclosures and presentations; whether data and results from current studies support further development of a program; and the potency, efficacy or safety of Arcus’s investigational products. All forward-looking statements involve known and unknown risks and uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements.

Wainberg的引用和声明涉及：分析的时间和范围，数据披露和演示；当前研究的数据和结果是否支持项目的进一步发展；以及Arcus研究产品的效力，功效或安全性。所有前瞻性陈述都涉及已知和未知的风险和不确定性以及其他重要因素，这些因素可能会导致Arcus的实际结果、绩效或成就与前瞻性陈述中明示或暗示的结果、绩效或成就存在重大差异。

Factors that could cause or contribute to such differences include, but are not limited to: risks associated with preliminary and interim data not being guarantees that future data will be similar; the unexpected emergence of adverse events or other undesirable side effects; difficulties or delays in initiating or conducting clinical trials due to difficulties or delays in the regulatory process, enrolling subjects or manufacturing or supplying product for such clinical trials; Arcus’s dependence on the collaboration with Gilead for the successful development and commercialization of its optioned molecules; difficulties associated with the management of the collaboration activities or expanded clinical programs; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical.

可能导致或促成此类差异的因素包括但不限于：与初步和中期数据相关的风险不能保证未来数据相似；意外出现不良事件或其他不良副作用；由于监管过程中的困难或延迟，招募受试者或制造或提供此类临床试验的产品，导致启动或进行临床试验的困难或延迟；Arcus依靠与吉利德的合作成功开发和商业化其选择性分子；与合作活动管理或扩大临床计划相关的困难；Arcus项目竞争格局的变化；以及与药品开发和临床相关的固有不确定性。

The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners.

Arcus名称和徽标是Arcus Biosciences，Inc.的商标。所有其他商标均属于其各自所有者。