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HAYWARD, Calif.--( BUSINESS WIRE )--Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, today announced results from Part 1 of ARC-10, a randomized, open-label, three-arm study evaluating domvanalimab, an Fc-silent anti-TIGIT monoclonal antibody, plus zimberelimab, an anti-PD-1 monoclonal antibody, (DZ) versus zimberelimab (Z) or chemotherapy in patients with front-line locally advanced or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50% without the presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved. This study was conducted in partnership with Gilead Sciences. These results will be presented on November 8 in a late-breaking poster session at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting by Melissa L. Johnson, M.D., Director of the Lung Cancer Research Program, Sarah Cannon Research Institute, and investigator for the ARC-10 study. “ Domvanalimab plus zimberelimab demonstrated a meaningful improvement in overall survival compared to zimberelimab alone, with a 36% reduction in risk of death and a median overall survival that will exceed two years,” said Melissa L. Johnson, M.D. “ These data provide further evidence that co-inhibiting the TIGIT and PD-1 pathways may result in a greater therapeutic benefit over inhibition of the PD-1 pathway alone.” “ These are the first results demonstrating an improvement in overall survival reported for domvanalimab and zimberelimab,” said Dimitry Nuyten, M.D., Ph.D., chief medical officer of Arcus. “ They add to the growing body of evidence that domvanalimab, an Fc-silent anti-TIGIT antibody, may have a differentiated efficacy, safety and tolerability profile relative to published data from studies with Fc-enabled anti-TIGIT antibodies.” At the time of data cutoff (DCO, May 17, 2024), 98 patients were randomized and 95 received treatment in Part 1 of the study. The median follow-up was 24.5 months, and as of the DCO, 22 patients remained on treatment (DZ, n=11; Z, n=10; chemo, n=1). Patient baseline demographics were generally balanced across the arms, with a slight imbalance of more patients with adenocarcinoma, ECOG status 0, and brain metastasis favoring the chemotherapy arm. A summary of efficacy results is below. Endpoint DZ (n=38) Z (n=40) Platinum-Doublet Chemo* (n=17) Overall Survival (OS) Median, months (95% CI) NR (13.7-NE) 24.4 (7.8-NE) 11.9 (2.7-NE) Hazard Ratio (95% CI) DZ vs Z 0.64 (0.32-1.25) DZ vs chemo 0.43 (0.20, 0.93) Z vs chemo 0.63 (0.30-1.29) 12-Month Survival Rate (95% CI) 68% 57% 50% Events, % (n) 36.8 (14) 52.5 (21) 70.6 (12) Progression-Free Survival (PFS)** Median, months (95% CI) 11.5 (4.0-26.2) 6.2 (2.5-12.3) 9.6 (2.6-16.4) Hazard Ratio (95% CI) DZ vs Z 0.69 (0.40-1.18) DZ vs chemo 0.69 (0.35, 1.38) Z vs chemo 1.07 (0.56-2.05) Events, % (n) 36.8 (14) 75.0 (30) 76.5 (13) Confirmed Objective Response Rate** % (n) [95% CI] 44.7 (17) [28.6-61.7] 35.0 (14) [20.6-51.7] 35.3 (6) [14.2-61.7] CI: confidence interval; NE: not evaluable; NR: not reached. *Carboplatin with either paclitaxel or pemetrexed. **Assessed per investigator according to RECIST v1.1. DZ and Z were generally well tolerated with no new safety concerns at the time of DCO. Treatment-related adverse events (TRAEs) leading to treatment discontinuation were higher for chemotherapy (23.5%) than for DZ (10.5%) and Z (7.5%). Infusion-related reactions were low (DZ, 7.9%; Z, 2.5%; chemotherapy, 0%). Grade ≥3 TRAEs were higher for chemotherapy (47.1%) than for DZ (21.1%) or Z (15.0%). TRAEs leading to death were lower for DZ (2.6%; n=1 sudden death) vs Z (10.0%; n=1 each sudden death, acute kidney injury, acute myocardial infarction, intestinal perforation) or chemotherapy (11.8%; n=1 each febrile neutropenia, ischemic stroke). Investors may dial into the earnings conference call at +1 (404) 975-4839 (local) or +1 (833) 470-1428 (toll-free), using Access Code: 940081, on Wednesday, Nov. 6, 2024, at 2:00 PM PT / 5:00 PM ET. Participants may also register for the call online using this link: https://www.netroadshow.com/events/login?show=4818aee3&confId=72838 . To access the live webcast and accompanying slide presentation, please visit the “Investors & Media” section of the Arcus Biosciences website at www.arcusbio.com . A replay will be available following the live event. About the ARC-10 Study ARC-10 was initially initiated and conducted as a randomized Phase 3 trial; the protocol was subsequently amended to evaluate domvanalimab plus zimberelimab versus pembrolizumab (part 2). Part 1 of the ARC-10 study is a multicenter, randomized, open-label study for patients with front-line locally advanced or metastatic squamous or non-squamous NSCLC with PD-L1 TPS ≥50% without the presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved. The study randomized patients 2:2:1 across the three study arms to receive every three weeks: (1) 15 mg/kg of domvanalimab plus 360 mg/kg of zimberelimab, (2) 360 mg/kg of zimberelimab or (3) platinum doublet chemotherapy in countries where anti-PD-(L)1 monotherapy was not yet standard of care. The primary endpoint was PFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The secondary endpoints were OS, confirmed ORR and safety. About Domvanalimab Domvanalimab is the most clinically advanced Fc-silent investigational monoclonal antibody that was specifically designed with Fc-silent properties to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activating immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity. Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to significantly enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity. Domvanalimab is being evaluated in combination with anti-PD-1 monoclonal antibodies, including zimberelimab, as well as other investigational cancer immunotherapies and A2a/A2b adenosine receptor antagonist etrumadenant, in multiple ongoing and planned early and late-stage clinical studies in various tumor types. About Zimberelimab Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the anti-tumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types. Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing and planned early and late-stage clinical studies in combination with other immunotherapies, including investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and A2a/A2b adenosine receptor antagonist etrumadenant. Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin's lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead. Domvanalimab and zimberelimab are investigational molecules. Arcus and Gilead have not received approval from any regulatory authority for any commercial use globally, and their safety and efficacy for the treatment of lung cancer have not been established. About 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- or 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. 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, HIF-2a, CD73, dual A2a/A2b receptor, CD39, and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com . Forward-Looking Statements 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. Nuyten’s and Dr. Johnson’s quotes and statements regarding the efficacy, safety or potential of domvanalimab and/or zimberelimab; the mechanisms of action for any of our investigational products; and current or future combinations involving our investigational products, including the potential benefit or effect of any such combinations. 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. Factors that could cause or contribute to such differences include, but are not limited to, risks associated with: interim data not being replicated in other ongoing or future studies evaluating the same investigational molecules or regimen; the unexpected emergence of adverse events or other undesirable side effects in Arcus’s investigational products, including domvanalimab and zimberelimab; Arcus’s dependence on the collaboration with Gilead for the successful development and commercialization of its optioned molecules, including domvanalimab and zimberelimab; difficulties associated with the management of the collaboration activities with our strategic partners or expanded clinical programs; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. Risks and uncertainties facing Arcus are described more fully in the “Risk Factors” section of Arcus’s most recent periodic report filed with the U.S. Securities and Exchange Commission. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Arcus disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release except to the extent required by law. The Arcus name and logo are trademarks of Arcus Biosciences, Inc. All other trademarks belong to their respective owners.

TOKYO, Japan & BASKING RIDGE, NJ, USA I October 30, 2024 I The first patients have been dosed in three global, randomized phase 3 trials evaluating the efficacy and safety of datopotamab deruxtecan (Dato-DXd)-based combinations in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). TROPION-Lung10 is evaluating datopotamab deruxtecan plus rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, or rilvegostomig alone versus pembrolizumab in patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (tumor cells [TC] ≥ 50%) and without actionable genomic alterations. TROPION-Lung14 is evaluating datopotamab deruxtecan plus osimertinib, AstraZeneca’s EGFR tyrosine kinase inhibitor (TKI), versus osimertinib alone in patients with previously untreated locally advanced or metastatic EGFR mutated nonsquamous NSCLC. TROPION-Lung15 is evaluating datopotamab deruxtecan with or without osimertinib versus platinum-based doublet chemotherapy in patients with locally advanced or metastatic nonsquamous EGFR mutated NSCLC whose disease progressed on prior treatment with osimertinib. “These three trials in either high PD-L1 expressing or EGFR mutated nonsquamous non-small cell lung cancer are critical to helping us understand the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “Our growing TROPION clinical program, which now consists of seven phase 3 trials demonstrates our commitment to understanding the full potential of datopotamab deruxtecan in lung cancer.” “Clinical research suggests that combining an antibody drug conjugate with a targeted treatment or a bispecific immunotherapy may drive stronger and more durable tumor responses in patients with a variety of cancers including lung cancer,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. “The initiation of these additional three phase 3 trials of datopotamab deruxtecan in combination with our agents, osimertinib and rilvegostomig illustrates our commitment to exploring potential synergies within our oncology pipeline as well as the full potential and combinability of this TROP2 directed antibody drug conjugate across multiple segments and settings of non-small cell lung cancer.” About TROPION-Lung10 TROPION-Lung10 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 2:1:2 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with rilvegostomig (750 mg) or rilvegostomig (750 mg) monotherapy versus pembrolizumab (200 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations. The dual primary endpoints of TROPION-Lung10 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS) in patients with TROP2 positive tumors receiving datopotamab deruxtecan in combination with rilvegostomig versus the pembrolizumab arm. A pre-specified retrospective analysis from tumor biopsies collected pretreatment will be conducted following validation of a potential TROP2 biomarker determined by quantitative continuous scoring, a computational pathology approach. Key secondary endpoints for all arms of the trial include PFS as assessed by BICR and investigator and OS in the intention-to-treat (ITT) population, objective response rate (ORR) as assessed by BICR and duration of response (DoR) as assessed by BICR and investigator in both TROP2 biomarker positive and the ITT populations. The safety and tolerability of datopotamab deruxtecan in combination with rilvegostomig and rilvegostomig monotherapy as compared with pembrolizumab also will be assessed. TROPION-Lung10 will enroll approximately 675 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN). About TROPION-Lung14 TROPION-Lung14 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with osimertinib (80 mg) versus osimertinib (80 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with an EGFR mutation (Exon 19 deletion and/or L858R). The randomized period of the trial is preceded by a single-arm safety run-in period which will enroll approximately 20 patients to evaluate the combination therapy. The primary endpoint of TROPION-Lung14 is PFS as assessed by BICR. Key secondary endpoints include central nervous system (CNS) PFS as assessed by CNS BICR, PFS as assessed by investigator, ORR as assessed by BICR and investigator, OS and safety. TROPION-Lung14 will enroll approximately 580 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About TROPION-Lung15 TROPION-Lung15 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 1:1:1 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) as monotherapy or in combination with osimertinib (80 mg) versus platinum-based doublet chemotherapy (pemetrexed in combination with carboplatin or cisplatin followed by pemetrexed maintenance) in adult patients with locally advanced or metastatic nonsquamous NSCLC with at least one EGFR mutation (G719X, Ex19del, S768I, L858R, and/or L861Q) and with disease progression following prior treatment with osimertinib. The dual primary PFS endpoints of TROPION-Lung15 are PFS as assessed by BICR for datopotamab deruxtecan monotherapy versus chemotherapy and datopotamab deruxtecan in combination with osimertinib versus chemotherapy. Key secondary endpoints include investigator-assessed CNS PFS as assessed by CNS BICR, ORR and DoR as assessed by BICR, OS and safety. TROPION-Lung15 will enroll approximately 630 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 NSCLC is the most common type of lung cancer, accounting for about 85% of cases. 2 Approximately 75% and 25% of NSCLC tumors are of nonsquamous or squamous histology, respectively, with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide. 3,4 A majority of EGFR mutations occur in tumors with nonsquamous histology. 5 For patients with tumors that do not express a known actionable genomic alteration (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET), the current first-line standard of care in the metastatic setting is an immune checkpoint inhibitor and/or platinum-based chemotherapy based on PD-L1 expression. 6,7,8 For certain patients with tumors that have EGFR mutations, the established first-line treatment in the metastatic setting is an EGFR TKI. 9 While these treatment strategies have improved outcomes in the first-line metastatic setting, most patients eventually experience disease progression. 10,11,12 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 13 There is currently no TROP2 directed ADC approved for the treatment of lung cancer. 8,9 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . References 1 World Health Organization. Global Cancer Observatory: Lung . Accessed October 2024. 2 Economopoulou P, et al. Ann Transl Med . 2018; 6(8):138 3 National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer, CSR 1975-2017 . Accessed October 2024. 4 Pretelli G, et al. Int J Mol Sci . 2023; 24, 8878. 5 Prabhakar C. Translational Lung Cancer Research . 2015; 4(2), 110-118. 6 Mok TSK, et al. Lancet . 2019 May 4;393(10183):1819-1830. 7 Brahmer J.R. et al. KEYNOTE-024 5-year OS update . ESMO 2021 Virtual Congress. 2021 Sept 16 – 20; Abstract LBA51. 8 Rodríguez-Abreau D, et al. Ann Onc . 2021 Jul;32(7):881-895. 9 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed October 2024. 10 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 11 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 12 Pircher A, et al. Anticancer Research . 2020;70(5):287-294. 13 Mito R, et al. Pathol Int . 2020;70(5):287-294. SOURCE: Daiichi Sankyo