A Phase 2, Open-Label, Multicenter, Randomized Study Evaluating Neoadjuvant Therapy Targeting the Adenosine Immunosuppressive Pathway in Combination With Immune Checkpoint Blockade and Radiation Therapy in Patients With Advanced PANCreatic Ductal Adenocarcinoma Who Are Candidates for Surgical Resection

The purpose of this study is to combine standard radiation therapy with drugs that encourages the body's immune system against cancer cells and simultaneously adding drugs which also target the pathway that the tumor uses to evade the immune system (CD73 and A2a/b). The study hopes that these drugs will work in concert with radiation therapy to kill cancer cells.
The specific goal of this study is to ensure that treatment with zimberelimab and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor.

Start Date01 Jun 2024

Sponsor / Collaborator

Arcus Biosciences, Inc.

NCT04892875 / WithdrawnPhase 1IIT

A Phase Ib Study of Concurrent Chemoradiation in Combination With or Without PD1 Inhibitor AB122 Adenosine 2a Receptor / Adenosine 2b Receptor Inhibitor AB928 Therapies in Locally Advanced Head and Neck Cancers (PANTHEoN)

The purpose of this study is to test the safety and tolerability of chemotherapy and radiation in combination with the investigational study drugs zimberelimab (AB122) and etrumadenant (AB928) in subjects with a locally advances head or neck cancer. The study will also ask how the study drugs change the following:
The microbiome that lives in the mouth and on the skin
Immune cells as they respond to a skin wound
Scarring (fibrosis) caused by radiation
After completing a screening phase, subjects will be assigned to one of three cohorts:
Cohort 1: Subjects who will receive cisplatin, radiation and zimberelimab followed by zimberelimab only.
Cohort 2: Subjects who will receive cisplatin, radiation, zimberelimab and etrumadenant followed by zimberelimab and etrumadent.
Cohort 3: Subjects who will receive cisplatin and radiation followed by an observation period.
All three cohorts will be followed for a 24 months following the conclusion of the chemoradiation.

Start Date31 Dec 2023

Sponsor / Collaborator

Arcus Biosciences, Inc.

NCT05915442 / RecruitingPhase 2IIT

Phase II Single Arm Study Testing SBRT, Adenosine Signaling Modulation (AB680, AB928), and Immune Checkpoint Inhibition (AB122) for Men With Hormone Sensitive Oligometastatic Prostate Cancer

This study will evaluate the safety and effectiveness of a combination of study drugs including zimberelimab, etrumadenant, and quemliclustat in combination with metastasis-directed irradiation in men with hormone sensitive oligometastatic prostate cancer.
The study aims to test the hypothesis that targeted inhibition of the adenosine signaling axis (quemliclustat (CD73 antagonist) + etrumadenant (A2AR/A2BR antagonist)) and immune checkpoint inhibition (zimberelimab, α-PD-1) in combination with metastasis-directed stereotactic body radiation therapy (SBRT) will improve local control, progression-free survival (PFS), and hormone therapy-free survival and mitigate immunosuppressive changes to the tumor microenvironment (TME), compared to SBRT alone.

Start Date01 Jul 2023

Sponsor / Collaborator

Arcus Biosciences, Inc.

100 Clinical Results associated with Etrumadenant

100 Translational Medicine associated with Etrumadenant

100 Patents (Medical) associated with Etrumadenant

260

Literatures (Medical) associated with Etrumadenant

01 Sep 2023·Experimental eye research

Differential effects of purines and prostaglandins on hypoxia induced dilatation of porcine retinal vessels at different branching level ex vivo

Article

Author: Ernst, Charlotte ; Bek, Toke

The metabolic pathways leading from hypoxia to retinal vasodilatation can involve effects of both purines and prostaglandins, but the effects of these compounds at different vascular branching levels are unknown. The purpose of the present study was to investigate differential effects of purines and prostaglandins in hypoxia-induced dilatation of retinal arterioles, precapillary arterioles and capillaries ex vivo. Porcine hemiretinas were mounted in a tissue chamber while monitoring temperature, pH, and oxygen tension. The effect of hypoxia on the diameter of larger arterioles, precapillary arterioles and capillaries was studied in the presence of the ecto-nucleotidase inhibitor AOPCP, the nonselective P2 purinoreceptor antagonist PPADS, the A2B adenosine receptor antagonist MRS 1754, the A3 adenosine receptor antagonist MRS 1523, the EP1 receptor antagonist SC-19220, the EP2 receptor antagonist PF-04418948, the EP3 receptor antagonist L-798,106, the EP4 receptor antagonist L-161-982, the prostaglandin synthesis inhibitor ibuprofen, and ibuprofen combined with AOPCP or ATP. Hypoxia-induced dilatation in arterioles was reduced by the A2B adenosine receptor antagonist (p < 0.01) and increased by the EP2 and the EP3 receptor antagonists (p < 0.01 for both comparisons). In precapillary arterioles the dilatation was reduced by the EP2 receptor antagonist (p < 0.04) and increased by the EP1 receptor antagonist (p < 0.03), whereas in capillaries the dilatation was increased by both the A3 adenosine receptor antagonist (p < 0.01), by ibuprofen in combination with the unspecific ecto-nucleotidase inhibitor AOPCP (p = 0.04) and by the prostaglandin EP3 receptor antagonist. Hypoxia-induced dilatation of retinal vessels is influenced by adenosine A2B and A3 receptors, and by the prostaglandin EP1, EP2 and EP3 receptors. The effects mediated by these receptors differ at different branching levels of the resistance vessels.

01 Jun 2023·Communications chemistry

Crystal structure of adenosine A_2A receptor in complex with clinical candidate Etrumadenant reveals unprecedented antagonist interaction.

Article

Author: Schlegel, Jonathan G ; Markovic-Mueller, Sandra ; Cheng, Robert K Y ; Claff, Tobias ; Weiße, Renato H ; Sträter, Norbert ; Voss, Jan H ; Bucher, Denis ; Müller, Christa E ; Vaaßen, Victoria J

The G_s protein-coupled adenosine A_2A receptor (A_2AAR) represents an emerging drug target for cancer immunotherapy. The clinical candidate Etrumadenant was developed as an A_2AAR antagonist with ancillary blockade of the A_2BAR subtype. It constitutes a unique chemotype featuring a poly-substituted 2-amino-4-phenyl-6-triazolylpyrimidine core structure. Herein, we report two crystal structures of the A_2AAR in complex with Etrumadenant, obtained with differently thermostabilized A_2AAR constructs. This led to the discovery of an unprecedented interaction, a hydrogen bond of T88^3.36 with the cyano group of Etrumadenant. T88^3.36 is mutated in most A_2AAR constructs used for crystallization, which has prevented the discovery of its interactions. In-vitro characterization of Etrumadenant indicated low selectivity versus the A₁AR subtype, which can be rationalized by the structural data. These results will facilitate the future design of AR antagonists with desired selectivity. Moreover, they highlight the advantages of the employed A_2AAR crystallization construct that is devoid of ligand binding site mutations.

31 Dec 2022·Journal of enzyme inhibition and medicinal chemistry

Design, synthesis, and biological evaluation of triazole-pyrimidine-methylbenzonitrile derivatives as dual A_2A/A_2B adenosine receptor antagonists

Article

Author: Gong, Shizhou ; Lin, Tiantian ; Xu, Maolei ; Liu, Ming ; Zhang, Shumin ; Kou, Lijuan ; Xie, Zeping ; Fu, Xinzhen ; Li, Zhi ; Guo, Lin

A series of novel dual A_2A/A_2B AR antagonists based on the triazole-pyrimidine-methylbenzonitrile core were designed and synthesised. The A_2A AR antagonist cAMP functional assay results were encouraging for most target compounds containing quinoline or its open-ring bioisosteres. In addition, compound 7i displayed better inhibitory activity on A_2B AR (IC₅₀ 14.12 nM) and higher potency in IL-2 production than AB928. Moreover, molecular docking studies were carried out to explain the rationality of molecular design and the activity of compound 7i. Further studies on 7f and 7i revealed good liver microsomes stabilities and acceptable in vivo PK profiles. This study provides insight into the future development of dual A_2A/A_2B AR antagonists for cancer immunotherapy.

111

News (Medical) associated with Etrumadenant

10 Jun 2024

·www.biospace.com

Arcus Biosciences Completes Patient Enrollment in Phase 3 Trial Evaluating a Domvanalimab-Containing Regimen in First-Line Metastatic Upper GI Cancers

Domvanalimab is the only anti-TIGIT antibody in Phase 3 for upper gastrointestinal (GI) adenocarcinomas with the potential to be first-to-market for this patient population HAYWARD, Calif.--(BUSINESS WIRE)-- Arcus Biosciences, Inc., (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, today announced the completion of patient enrollment for STAR-221, a Phase 3 study in collaboration with Gilead Sciences, evaluating the combination of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 monoclonal antibody zimberelimab and chemotherapy in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma. “STAR-221 completed enrollment well ahead of schedule, driven by significant interest from the global medical community in the potential for an anti-TIGIT-based regimen to address the high unmet need in this setting,” said Dimitry S.A. Nuyten, M.D., Ph.D., chief medical officer of Arcus Biosciences. “Domvanalimab is the first and only anti-TIGIT antibody to be studied in a Phase 3 trial in upper gastrointestinal adenocarcinoma. We are now preparing for the readout and look forward to the potential opportunity to make a meaningful difference for patients with this disease.” Earlier this month at the American Society of Clinical Oncology (ASCO) Annual Meeting, Arcus and Gilead presented results from Arm A1 of the Phase 2 EDGE-Gastric study evaluating the same regimen in the same setting as the STAR-221 Phase 3 study. Data from this arm of EDGE-Gastric showed that patients treated with domvanalimab plus zimberelimab and chemotherapy had a median progression-free survival (PFS) of 12.9 months, which exceeds the historical benchmarks for anti-PD-1 plus chemotherapy alone. Notably, nearly 60% of patients in the EDGE-Gastric study achieved PFS at 12 months, and the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained improvement across efficacy measures, including in those patients who have low PD-L1 expression. No unexpected safety signals were observed at the time of data cutoff, March 12, 2024. The domvanalimab plus zimberelimab and chemotherapy regimen was generally well tolerated and showed an overall safety pro with the known safety profiles of each individual molecule to date. Domvanalimab and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of gastrointestinal cancers have not been established. About the STAR-221 Study The ongoing, global STAR-221 trial (NCT05568095) enrolled approximately 1,050 participants with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. The primary endpoints of the study are overall survival in PD-L1-high tumors and in the intent-to-treat population (all PD-L1 levels); secondary endpoints include progression-free survival, objective response rate and duration of response. Participants were randomized 1:1 between two arms: 1600 mg of domvanalimab intravenously (IV) every four weeks plus 480 mg of zimberelimab IV every four weeks plus FOLFOX (oxaliplatin, leucovorin, fluorouracil) every two weeks or 1200 mg of domvanalimab plus 360 mg of zimberelimab every three weeks plus CAPOX (capecitabine and oxaliplatin) every three weeks 240 mg of nivolumab IV every two weeks plus FOLFOX every two weeks or 360 mg of nivolumab plus CAPOX every three weeks About Domvanalimab Domvanalimab is the first and most clinically advanced Fc-silent investigational monoclonal antibody that is 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 activate 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 antitumor 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. 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, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . Arcus 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 quote and statements regarding the potential for domvanalimab to be first anti-TIGIT to market for upper GI cancers. 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 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; risks associated with the manufacturing or supplying product for such clinical trials; uncertainties in timelines associated with the conduct of clinical studies and with respect to the regulatory application process; 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 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.

Clinical ResultPhase 3ImmunotherapyASCODrug Approval

02 Jun 2024

·www.biospace.com

Gilead and Arcus Announce Etrumadenant Plus Zimberelimab Regimen Significantly Reduced the Risk of Death in Third-line Metastatic Colorectal Cancer

In Cohort B of the ARC-9 mCRC Study, Etrumadenant Plus Zimberelimab, FOLFOX Chemotherapy and Bevacizumab Significantly Reduced the Risk of Death by 63% and Risk of Disease Progression by 73% Compared to Regorafenib in a Phase 1b/2 Trial Results will be Presented Today During an Oral Session at the ASCO Annual Meeting FOSTER CITY, Calif. & HAYWARD, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) today announced new data from Cohort B of ARC-9, a Phase 1b/2 study evaluating the safety and efficacy of etrumadenant, a dual A2a/b adenosine receptor antagonist, plus anti-PD-1 monoclonal antibody zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) in third-line metastatic colorectal cancer (mCRC). These results will be presented today during an oral session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting by Zev A. Wainberg, M.D., MSc, Co-Director of the GI Oncology Program at University of California Los Angeles and a principal investigator of the ARC-9 trial (Abstract 3508). This press release features multimedia. View the full release here: “ARC-9 is the first randomized Phase 2 study to show that combining an adenosine receptor blocker with anti-PD-1, anti-VEGF and chemotherapy can meaningfully improve clinical outcomes for people with metastatic colorectal cancer who have progressed on at least two prior therapies,” said Dr. Wainberg. “19.7 months is the longest median overall survival reported in third-line mCRC and warrants further investigation of an etrumadenant-based regimen as a potential treatment option in CRC1.” Cohort B of ARC-9 randomized 112 patients with comparable baseline characteristics between two arms: EZFB or regorafenib. At the time of data cut-off (November 13, 2023) median follow-up was 20.4 months. Patient baseline characteristics were similar to those of third-line patients who have progressed on oxaliplatin- and irinotecan-based regimens in mCRC1. OS and PFS were consistently longer in the EZFB arm versus regorafenib, in all sub-groups analyzed, including in patients with liver metastases. Summary of efficacy results: EZFB* n=75 regorafenib n=37 Median OS, months 19.7 9.5 Hazard Ratio (95% CI), P-value HR 0.37 95% CI 0.22-0.63 p=0.0003 Median PFS, months 6.2 2.1 Hazard Ratio (95% CI), P-value HR 0.27 95% CI 0.17-0.43 p<0.0001 Confirmed ORR 13 (17.3%) 1 (2.7%) Median DOR, months 11.5 NE CI: confidence interval OS: overall survival PFS: progression-free survival ORR: objective response rate DOR: duration of response NE: not evaluable; only one patient with response *bevacizumab was included for all patients in whom it is not contraindicated The EZFB regimen had a safety pro with the known safety profiles of each individual molecule to date, without unexpected toxicities. A higher percentage of patients treated with regorafenib (17%) had a treatment emergent adverse event (TEAE) leading to discontinuation of all study drugs than those treated with EZFB (5%). A lower percentage of patients experienced Grade ≥3 TEAEs attributed to etrumadenant or zimberelimab versus regorafenib (23.0% vs 25.7%). Etrumadenant and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of colorectal cancer have not been established. About the ARC-9 Study ARC-9 (NCT04660812) is a Phase 1b/2 trial evaluating the safety and efficacy of etrumadenant (E), a dual A2a/A2b adenosine receptor antagonist, plus anti-PD-1 antibody zimberelimab (Z), FOLFOX and bevacizumab (if not contraindicated) in three cohorts of patients with mCRC. The primary endpoint is PFS per RECIST 1.1, and OS is a key secondary endpoint. Cohort B enrolled patients who previously progressed on both oxaliplatin- and irinotecan-containing chemotherapy in combination with anti-VEGF (R) therapy or anti-EGFR. Patients were randomized 2:1 to the etrumadenant plus zimberelimab regimen: E (150 mg orally [PO] once daily [QD]) + Z (240 mg intravenous [IV] once every 2 weeks [Q2W]) + mFOLFOX-6 + bevacizumab (5 mg/kg IV Q2W), or regorafenib (administered at a starting dose of 80 mg/day for the first week, followed by a dose escalation of 40 mg every week to 120 mg/day for the second week and 160 mg/day for the third week during Cycle 1 followed by 160 mg/day on Days 1-21 of each subsequent 28-day cycle). Patients who progressed on regorafenib were allowed to crossover to the etrumadenant plus zimberelimab regimen. ARC-9 is a multi-cohort study in mCRC including Cohort A, which enrolled patients who previously progressed on FOLFOX/FOLFIRI in combination with anti-VEGF(R) or anti-EGFR. Patients were randomized 2:1 to the etrumadenant plus zimberelimab regimen, or FOLFOX-6 + bevacizumab. Data from Cohort A will be presented when they are mature. About Etrumadenant Etrumadenant is an investigational small molecule, selective dual antagonist of the A2a and A2b receptors designed to prevent adenosine-mediated immunosuppression. Adenosine elicits its immunosuppressive effects within the tumor microenvironment by binding and activating adenosine-specific receptors expressed on the surface of tumor-infiltrating immune cells, which can help cancer cells evade host antitumor immunity. Once etrumadenant binds to the A2a and A2b receptors and blocks the immunosuppressive effects of adenosine, activation of antitumor immune cells may be restored, which could result in tumor cell death. Etrumadenant is being evaluated in combination with other cancer immunotherapies, including the investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and anti-PD-1 monoclonal antibody zimberelimab, in certain types of non-small cell lung and colorectal cancers. 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 antitumor 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. 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, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Arcus 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. Wainberg quote and statements regarding: whether data and results from the ARC-9 study validate our pipeline or support further development of etrumadenant and/or zimberelimab. 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 changing as patient enrollment continues and more patient data becomes available; interim data not being replicated in 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; 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 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. Gilead Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving etrumadenant and zimberelimab (such as the ARC-9 study); uncertainties relating to regulatory applications and related filing and approval timelines, and the risk that any such approvals, if granted, may be subject to significant limitations on use; the possibility that Gilead may make a strategic decision to discontinue development of etrumadenant and zimberelimab for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for such indications; the risk that Gilead may not realize the potential benefits of its collaboration with Arcus or its other investments in oncology; difficulties or unanticipated expenses in connection with the collaboration and the potential effects on Gilead’s revenues and earnings; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies. Arcus name and logo are trademarks of Arcus Biosciences, Inc. For more information about Gilead, please visit the company’s website at , follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences). ___________________________________ 1 Prager GW, et al. Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. N Engl J Med. 2023;388(18):1657-1667. doi: 10.1056/NEJMoa2214963. PMID: 37133585. View source version on businesswire.com: Contacts Meaghan Smith, Gilead Media public_affairs@gilead.com Jacquie Ross, Gilead Investors investor_relations@gilead.com Pia Eaves, Arcus Investors peaves@arcusbio.com, (617) 459-2006 Holli Kolkey, Arcus Media hkolkey@arcusbio.com, (650) 922-1269 Source: Gilead Sciences, Inc. View this news release online at:

Clinical ResultImmunotherapyASCOPhase 2Drug Approval

01 Jun 2024

·www.biospace.com

Gilead and Arcus Announce Anti-TIGIT Domvanalimab Plus Zimberelimab and Chemotherapy Exceeded One Year of Median Progression-Free Survival as a First-Line Treatment for Upper GI Cancers

Data Support the Ongoing Phase 3 STAR-221 Study of Domvanalimab Plus Zimberelimab and Chemotherapy, Potentially the First Anti-TIGIT Combination to Market for These Cancers Results will be Presented Today During an Oral Session at the ASCO Annual Meeting FOSTER CITY, Calif. & HAYWARD, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) today announced longer-term efficacy and safety results from Arm A1 of the Phase 2 EDGE-Gastric study. These updated data show consistent objective response rate (ORR) and provide mature progression-free survival (PFS) in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma (upper GI cancers). The ongoing, multi-arm, global Phase 2 EDGE-Gastric study is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 monoclonal antibody zimberelimab and chemotherapy in this patient population. These results will be presented today during the American Society of Clinical Oncology (ASCO) Plenary Series: Rapid Abstract Updates session by Yelena Y. Janjigian, M.D., Chief, Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, and a principal investigator for the EDGE-Gastric study (Abstract 433248). This press release features multimedia. View the full release here: “I am encouraged to see that patients treated with domvanalimab plus zimberelimab and chemotherapy had a median progression-free survival beyond one year, which exceeds the historical benchmarks for anti-PD-1 plus chemotherapy alone,” said Dr. Janjigian. “Notably, nearly 60% of patients in the EDGE-Gastric study achieved progression-free survival at 12 months. These promising results reinforce our confidence in the ongoing Phase 3 STAR-221 study, which evaluates the same regimen in the same patient population and has the potential to address a high unmet need for people with these cancers.” At data cutoff (DCO, March 12, 2024), safety and efficacy were evaluated in all patients enrolled and treated (n=41). With a median time on treatment of 49.4 weeks (range: 0.4 - 79.4 weeks), the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained improvement across efficacy measures, including in those patients who have low PD-L1 expression. Summary of efficacy results: Endpoint Overall* PD-L1-high PD-L1-low n=41 (TAP ≥5%) (TAP <5%) n=16 n=24 Progression-Free Survival (PFS) Median in Months (95% CI) 12.9 mos (9.8, 13.8) 13.8 mos (11.3, NE) 11.3 mos (5.5, 13.8) 12-month PFS Rate (95% CI) 57.6% (41.7,73.5) 68.8% (46.0, 91.5) 46.8% (24.7, 68.9) Objective Response Rate (ORR) per RECIST v1.1 Confirmed ORR (95% CI) 58.5% (42.1, 73.7) 68.8% (41.3, 89.0) 50.0% (29.1, 70.9) Complete Response 3 (7.3%) 1 (6.3%) 1 (4.2%) Partial Response 21 (51.2%) 10 (62.5%) 11 (45.8%) Stable Disease 14 (34.1%) 5 (31.3%) 9 (37.5%) Progressive Disease Confirmed 2 (4.9%) 0 2 (8.3%) Not Evaluable** 1 (2.4%) 0 1 (4.2%) Median Duration of Response (DOR) in Months 12.4 mos (9.9, NE) NE (11.5, NE) 10.2 mos (4.0, 12.4) *One subject with no tissue available for central PD-L1 testing. From local lab results, the subject is PD-L1 low via 22-C3 assay. This subject achieved confirmed complete response. ** One subject has no post baseline scans. CI: confidence interval NE: not evaluable TAP: tumor area positivity No unexpected safety signals were observed at the time of DCO. The domvanalimab plus zimberelimab and chemotherapy regimen was generally well tolerated and showed an overall safety pro with the known safety profiles of each individual molecule to date. Infusion-related reactions were observed in 19.5% of the total subjects, and the majority were related to chemotherapy. The updated data from Arm A1 of the Phase 2 EDGE-Gastric study support the ongoing Phase 3 STAR-221 study, in unresectable or metastatic upper GI cancers, which is expected to complete enrollment mid-year 2024. Domvanalimab and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of gastrointestinal cancers have not been established. About the EDGE-Gastric Study The ongoing, multi-arm, multi-cohort global Phase 2 EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the Fc-silent anti-TIGIT antibody domvanalimab and the anti-PD-1 monoclonal antibody zimberelimab in patients with locally advanced unresectable or metastatic gastric (G), gastroesophageal junction (GEJ) or esophageal (E) adenocarcinoma. Patients in Arm A1, with previously untreated G/GEJ/E adenocarcinoma, received 1600 mg of domvanalimab intravenously (IV) every four weeks (Q4W) plus 480 mg of zimberelimab IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) every two weeks. About Domvanalimab Domvanalimab is the first and most clinically advanced Fc-silent investigational monoclonal antibody that is 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 activate 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 antitumor 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. 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, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Arcus 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. Janjigian’s quote and statements regarding: whether data and results from the EDGE-Gastric study reinforces our confidence in our Phase 3 STAR-221 study and the potential of this regimen to address a high unmet need for people with upper GI cancers; the potential for domvanalimab in combination with zimberelimab and chemotherapy to be first anti-TIGIT combination to market for upper GI cancers; and the timing of upcoming milestones. 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 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; risks associated with the manufacturing or supplying product for such clinical trials; uncertainties in timelines associated with the conduct of clinical studies and with respect to the regulatory application process; 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 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. Gilead Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving domvanalimab and zimberelimab (such as the EDGE-Gastric and STAR-221 studies); uncertainties relating to regulatory applications and related filing and approval timelines, and the risk that any such approvals, if granted, may be subject to significant limitations on use; the possibility that Gilead may make a strategic decision to discontinue development of domvanalimab and zimberelimab for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for such indications; the risk that Gilead may not realize the potential benefits of its collaboration with Arcus or its other investments in oncology; difficulties or unanticipated expenses in connection with the collaboration and the potential effects on Gilead’s revenues and earnings; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies. Arcus name and logo are trademarks of Arcus Biosciences, Inc. For more information about Gilead, please visit the company’s website at , follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences). _________________________________ Dr. Janjigian has served as a consultant to Arcus Biosciences; she has not been paid for any media work. View source version on businesswire.com: Contacts Meaghan Smith, Gilead Media public_affairs@gilead.com Jacquie Ross, Gilead Investors investor_relations@gilead.com Pia Eaves, Arcus Investors peaves@arcusbio.com, (617) 459-2006 Holli Kolkey, Arcus Media hkolkey@arcusbio.com, (650) 922-1269 Source: Gilead Sciences, Inc. View this news release online at:

Clinical ResultImmunotherapyPhase 2ASCODrug Approval

100 Deals associated with Etrumadenant

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Dedifferentiated Liposarcoma	Phase 2	US	Memorial Sloan Kettering Cancer Center	23 May 2023
Soft Tissue Sarcoma	Phase 2	US	Memorial Sloan Kettering Cancer Center	23 May 2023
Metastatic castration-resistant prostate cancer	Phase 2	US	Coherus BioSciences, Inc.	17 Jan 2022
Metastatic castration-resistant prostate cancer	Phase 2	CA	Coherus BioSciences, Inc.	17 Jan 2022
small cell carcinoma non	Phase 2	US	Arcus Biosciences, Inc.	04 Aug 2021
Metastatic Colorectal Carcinoma	Phase 2	US	Arcus Biosciences, Inc.	10 May 2021
Metastatic Colorectal Carcinoma	Phase 2	FR	Arcus Biosciences, Inc.	10 May 2021
Metastatic Colorectal Carcinoma	Phase 2	IT	Arcus Biosciences, Inc.	10 May 2021
Metastatic Colorectal Carcinoma	Phase 2	KR	Arcus Biosciences, Inc.	10 May 2021
Metastatic Colorectal Carcinoma	Phase 2	ES	Arcus Biosciences, Inc.	10 May 2021

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04660812 (ARC-9, ASCO2024) Manual	Phase 1/2	Metastatic Colorectal Carcinoma	112	Etrumadenant+zimberelimab+mFOLFOX-6±bevacizumab	ssurrvutew(ztqcjvaavl) = frtewyustc plmtgortme (xujwoyxylp, 5.5 - 7.5) View more	Positive	24 May 2024
				regorafenib	ssurrvutew(ztqcjvaavl) = xivkijuizy plmtgortme (xujwoyxylp, 1.8 - 3.0) View more
NCT05177770 (CTgov)	Phase 2	Metastatic castration-resistant prostate cancer	16	SRF617+Etrumadenant+Zimberelimab	qmjpvvzvpd(wcxarhjhsw) = ccxmfnuhxw ysavnhreer (ubuqidjdhb, zxefrcvqrm - jjtloyjjvx) View more	-	17 May 2024
NCT03555149 (MORPHEUS, CTgov)	Phase 1/2	Metastatic Colorectal Carcinoma	96	Regorafenib (Regorafenib (Control))	bqenjjrdiw(kcoclzxbxp) = dzvmpvhvtf arwxbgjjbe (oplnjawjto, rekoyqeems - boyawswjdp) View more	-	07 Nov 2023
				Imprime PGG+Atezolizumab+Bevacizumab (Atezolizumab + Imprime PGG + Bevacizumab)	bqenjjrdiw(kcoclzxbxp) = fjcvostrct arwxbgjjbe (oplnjawjto, lenqiduund - mxjafqpnjt) View more
NCT04262856 (ARC-7, Corporate Publications) Manual	Phase 2	Non-Small Cell Lung Cancer First line	150	zimberelimab	ohplkstdcr(cmfuxgjtct) = dwzybdnoqc pkcbgjjcvk (rtxevwwctj, 17.9 - 44.6) View more	Positive	03 Jun 2023
				domvanalimab + zimberelimab	ohplkstdcr(cmfuxgjtct) = ajsacpxenc pkcbgjjcvk (rtxevwwctj, 26.4 - 54.8) View more
NCT04262856 (ARC-7, ASCO2022) Manual	Phase 2	metastatic non-small cell lung cancer First line PD-L1 High Expression	149	zimberelimab	lasjxvxrkf(vtfrvxbexp) = wkctwqwbjv xdukqfpdxy (pxevkwxdez, 15.0 - 42.8) View more	Positive	20 Dec 2022
				domvanalimab+zimberelimab	lasjxvxrkf(vtfrvxbexp) = nmjyoorive xdukqfpdxy (pxevkwxdez, 26.3 - 56.8) View more
NCT04381832 (ARC-6, ASCO2021) Manual	Phase 1/2	Castration-Resistant Prostatic Cancer	-	zimberelimab+docetaxel+etrumadenant	yfyddbpgrw(thlxbpfvez) = yrbuwpumxl dhzlrnliof (qqlhsfbxoe ) View more	Positive	28 May 2021
NCT03720678 (ARC-3, AACR2021) Manual	Phase 1	Metastatic Colorectal Carcinoma	44	mFOLFOX-6+AB928	zsatwnhfpf(furazbxrmd) = knqeffiibc ghdwystmxq (wvvratejii ) View more	Positive	10 Apr 2021
				mFOLFOX-6+AB928 (3L+ pts)	qevkgfbxcp(fdeahxsjhy) = uzuxifhdya dselprfvhr (hveigpjzzl ) View more
NCT03719326 (ARC-2, AACR2021) Manual	Phase 1	Ovarian Cancer \| Metastatic Triple-Negative Breast Carcinoma	29	AB928 150 mg + pegylated liposomal doxorubicin (Doublet)	tthtaxknhc(udpgwuhebb) = Four pts reported 6 Gr ≥3 SAEs njakbwvnbr (njbrtdxqxw ) View more	Positive	15 Feb 2021
				IPI-549 40 mg + AB928 150 mg + pegylated liposomal doxorubicin (Triplet)
NCT03846310 (ARC-4, ESMO2020) Manual	Phase 1	metastatic non-small cell lung cancer	11	AB928+carboplatin+pemetrexed+zimberelimab	pztvlzjxgh(godnkwyrym) = Two pts experienced SAEs (Gr4 thrombocytopenia [n=1], pyrexia, vomiting, rash [n=1]) that were related to AB928. eogjrsjtzi (sutilsjcio ) View more	Positive	17 Sep 2020
NCT03720678 (ARC-3, AACR2020)	Phase 1	Metastatic Colorectal Carcinoma	40	AB928 150 mg + mFOLFOX-6	vkmlcyiary(wjweezbcic) = AB928-related Grade 3 AEs reported by 3 pts were diarrhea, AST increase, and neutropenia; there were no Grade 4-5 AB928-related AEs jgjvhdjhdt (opnoxyamzq ) View more	-	15 Aug 2020

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Etrumadenant

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation