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

June 2, 2024

– 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 –

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).

“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 CRC.”

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 mCRC. 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 profile consistent 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 www.arcusbio.com.

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 www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).

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: Arcus Biosciences