etrumadenant (AB928) / Arcus Biosci, Otsuka - LARVOL DELTA

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=290 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2022 ➔ Jun 2024 | Trial primary completion date: Nov 2022 ➔ Jun 2024

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=290 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=290 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Nov 2021 ➔ Nov 2022 | Trial primary completion date: Nov 2021 ➔ Nov 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=340 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=341 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=205 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2020 ➔ Feb 2022 | Trial primary completion date: Nov 2019 ➔ Feb 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=260 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Feb 2022 ➔ Nov 2021 | Trial primary completion date: Feb 2022 ➔ Nov 2021

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=340 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2026 ➔ Jan 2025 | Trial primary completion date: Oct 2025 ➔ Jan 2025

Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=205 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Apr 2020 ➔ Sep 2020

Trial completion date • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=290 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=185 | Recruiting | Sponsor: Hoffmann-La Roche

New P1/2 trial • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • PD-L1

MORPHEUS-PDAC: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer) (clinicaltrials.gov) - P1/2 | N=340 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2024 ➔ Oct 2026 | Trial primary completion date: Jun 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

The Randomized Phase 2 ARC-9 Study of Etrumadenant-Based Therapy vs Regorafenib in Patients with Previously Treated Metastatic Colorectal Cancer. (PubMed, Clin Cancer Res) - P1/2 | "EZFB significantly improved survival outcomes compared with regorafenib in patients with mCRC as a third-line treatment, with a manageable safety profile. Further investigation is warranted, given the clinically meaningful improvements in progression-free survival and overall survival."

Journal • P2 data • Colorectal Cancer • Oncology • Solid Tumor

VELOCITY-Lung: Study of Novel Treatment Combinations in Patients With Lung Cancer (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: Gilead Sciences | N=593 ➔ 270

Enrollment change • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

A Phase 2 Study to Evaluate the Triplet Combination of Pemetrexed Plus AB928 (Etrumadenant) + AB122 (Zimberelimab) in Patients With Previously Treated Advanced or Metastatic MTAP Deficient Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | N=20 ➔ 10

Enrollment change • Enrollment closed • Oncology • Solid Tumor • Urothelial Cancer • IL17A • MTAP

The clinical benefit from treatment of advanced MSS mCRC with the adenosine 2a/2b antagonist etrumadenant is associated with adenosine-mediated T-cell exclusion and enhancement of the effectiveness of immunotherapy (AACR-IO 2026) - P1/2 | "Etruma, in combination with zimberelimab (Z) (an anti-PD-1 antibody) and FOLFOX/bevacizumab (bev) (EZFB regimen) demonstrated a significant overall survival (OS) benefit over regorafenib (rego) in third-line, MSS, chemo-resistant mCRC in the ARC-9 Ph2 study (NCT04660812)... The majority of ARC-9 patients were shown to have CD73+, T cell excluded tumors and experienced robust clinical benefit on EZFB regardless of CD73 or PD-L1 status. Patients with CD73+ PD-L1high tumors derived the greatest benefit, supporting the hypothesis that clinical efficacy on this regimen is fundamentally underpinned by reversal of T cell exclusion and reinvigoration of T cell mediated anti-tumor immunity in the late-line, MSS chemo-resistant mCRC. Citation Format: Jiyun Kim, Emily Brown, Shravani Shitole, Madhura Joglekar, Haben Ghermazien, Jose Aquino, Tingting Zhao, Jennifer Scott, Soonweng Cho, Angelo Kaplan, Omar Kabbarah."

Clinical • IO biomarker • Metastases • Colorectal Cancer • Solid Tumor • CD73 • CD8 • GZMB • NT5E • PD-L1

ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC). (ASCO 2024) - P1/2 | "ARC-9 (NCT04660812), a Phase Ib/II trial evaluating the safety and efficacy of E combined with zimberelimab (Z) (anti-PD-1 antibody), and FOLFOX/bevacizumab (bev) regimens or novel therapies in 3 cohorts of patients (pts) with mCRC... Cohort B enrolled pts who previously progressed on both oxaliplatin and irinotecan containing regimens.Pts were randomized 2:1 to EZFB: E (150 mg orally [PO] once daily [QD]) + Z (240 mg intravenous [IV] once every 2 weeks [Q2W]) + mFOLFOX-6 + bev (5 mg/kg IV Q2W), or regorafenib (rego) (160 mg PO QD [days 1-21 every 4 weeks])... In this randomized phase II clinical trial, EZFBsignificantlyimproved efficacy outcomes compared to rego in refractory mCRC pts previously treated with 5-FU, oxaliplatin and irinotecan regimens with no unexpected toxicities. Further investigation of this promising regimen is warranted given the clinically meaningful PFS and OS improvement. Table"

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ARC-7: Randomized phase 2 study of domvanalimab + zimberelimab ± etrumadenant versus zimberelimab in first-line, metastatic, PD-L1-high non-small cell lung cancer (NSCLC). (ASCO Plenary Dec 2022) - P2 | "NCT04262856"

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Updates on Abstract 397600: ARC-7: Randomized phase 2 study of domvanalimab + zimberelimab ± etrumadenant versus zimberelimab in first-line, metastatic, PD-L1-high non-small cell lung cancer (NSCLC) (ASCO 2023) - No abstract available

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A phase 2 single-arm study testing SBRT, adenosine signaling modulation, and immune checkpoint inhibition for men with hormone-sensitive oligometastatic prostate cancer (SBRT-AMICO). (ASCO-GU 2024) - P2 | " SBRT-AMICO is a single-arm phase 2 trial testing the combination of a CD73 inhibitor (AB680), A2AR/A2BR inhibitor (AB928), and anti-PD-1 (AB122) with metastasis-directed SBRT for omHSPC. Arterioscler Thromb Vasc Biol, 2012. Clinical trial information: NCT05915442."

Checkpoint inhibition • Metastases • P2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD73 • ENTPD1

Reversing adenosine-mediated immunosuppression in triple-negative breast cancer by synergistic chemo-immunotherapy via stimuli-responsive nanomedicines. (PubMed, EBioMedicine) - "Co-delivery of an ICD inducer (EPI) and an adenosine receptor antagonist (AB928) is realised in a stimuli-responsive nanomedicine to address immunosuppression induced by adenosine, thereby enhancing ICD effects and synergistically reprogramming the immunosuppressive tumor microenvironment."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ADORA2A • CTSB

Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2029 ➔ Jun 2030 | Trial primary completion date: Oct 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Pilot Study to Evaluate the Combination of Zimberelimab, Domvanalimab and Etrumadenant in Patients with Previously Treated Non-Small Cell Lung Cancer (NSCLC) (SITC 2025) - "Biomarker analyses are planned.Trial Registration NCT04791839Ethics Approval The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice (ICH GCP) and approved by the Washington University Human Research Protection Office (IRB ID #: 202104122). All participants signed informed consent before taking part on the study."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TIGIT

ARC-9: An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov) - P1/2 | N=227 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Sep 2025

Trial completion • Trial completion date • Colorectal Cancer • Oncology • Solid Tumor

Discovery of Novel Triple A1/A2A/A2B Adenosine Receptor Antagonists for Cancer Immunotherapy. (PubMed, J Med Chem) - "Compound 14a also effectively restored T cell proliferation suppressed by 5'-N-ethylcarboxamidoadenosine (NECA) and exhibited superior T cell-mediated cytotoxicity in coculture systems with A1R- and PD-L1-expressed cancer cells compared with ciforadenant (A2AR antagonist) and etrumadenant (A2AR/A2BR dual antagonist). Moreover, the combination of compound 14a with avelumab, an anti-PD-L1 antibody, resulted in enhanced infiltration of effector T cells and significantly increased the CD8+/Treg ratio in the CT26 syngeneic mouse model, substantially inhibiting tumor growth. Therefore, compound 14a is a promising candidate for multitargeted immunomodulation in cancer immunotherapy."

Journal • Immunology • Oncology • CD8