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

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

VELOCITY-Lung: Study of Novel Treatment Combinations in Patients With Lung Cancer (clinicaltrials.gov) - P2 | N=593 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Dec 2028 ➔ Sep 2029 | Trial primary completion date: Jan 2027 ➔ Sep 2029

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

PANTHER: A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for Rectal Cancer. (clinicaltrials.gov) - P2 | N=43 | Recruiting | Sponsor: Weill Medical College of Cornell University | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial primary completion date • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

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 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Aug 2025 ➔ Mar 2026 | Trial primary completion date: Jul 2025 ➔ Oct 2025

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

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=151 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • 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=20 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2027 | Trial primary completion date: Sep 2025 ➔ Sep 2027

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer • IL17A • MTAP

VELOCITY-Lung: Study of Novel Treatment Combinations in Patients With Lung Cancer (clinicaltrials.gov) - P2 | N=593 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Jan 2027 ➔ Dec 2028

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

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 primary completion date: Jul 2025 ➔ Oct 2025 | Trial completion date: Sep 2029 ➔ Dec 2029

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

Arcus Biosciences Reports Second-Quarter 2025 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights:...Etrumadenant (adenosine A2a/A2b receptor antagonist): In March 2025, we engaged with the FDA regarding promising results from the ARC-9 study evaluating etrumadenant in third-line metastatic colorectal cancer (mCRC); although the FDA’s feedback confirmed the potential for a registrational path for this program in third-line mCRC, based on our strategic priorities, Arcus and Gilead agreed to not pursue a Phase 3 study at this time and, in June 2025, Gilead returned its license to etrumadenant to Arcus."

FDA event • Licensing / partnership • Pipeline update • Colorectal Cancer

Design, synthesis, and biological evaluation of A2A adenosine receptor antagonists containing pyrrolo[2,3-d]pyrimidin-2-amine skeleton. (PubMed, Bioorg Chem) - "Notably, compounds 12a and 18e demonstrated superior inhibitory effects compared to the control compounds AB928 and ZM241385...Compound 12a also demonstrated favorable stabilities in liver microsomes and acceptable pharmacokinetic profiles in vivo. These findings underscore the promise of compound 12a as a leading candidate for further research and development, highlighting its potential therapeutic applications."

Journal

Neoadjuvant Atezolizumab-Based Combination Therapy in Men With Localized Prostate Cancer Prior to Radical Prostatectomy (clinicaltrials.gov) - P2 | N=68 | Recruiting | Sponsor: David Oh | N=26 ➔ 68 | Active, not recruiting ➔ Recruiting

Enrollment change • Enrollment open • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

SBRT-AMICO: Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer (clinicaltrials.gov) - P2 | N=23 | Recruiting | Sponsor: Catherine Spina | Trial primary completion date: Dec 2025 ➔ Dec 2026

Checkpoint inhibition • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Recruiting ➔ Active, not recruiting | N=25 ➔ 16

Enrollment change • Enrollment closed • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

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: Apr 2029 ➔ Sep 2029 | Trial primary completion date: Jan 2025 ➔ Jul 2025

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

Phase Ib/II open-label, randomized study of atezolizumab + regorafenib + AB928 or atezolizumab + regorafenib vs regorafenib for patients with microsatellite-stable, refractory metastatic colorectal cancer in MORPHEUS-CRC (AACR 2025) - P1/2 | "Atezo + rego ± AB928 did not have sufficient clinical activity to merit further evaluation in an unselected mCRC population. Consistent with other reports of PD-(L)1-directed immunotherapy in mCRC, durable responses were observed in pts without liver metastases.EfficacyAtezo + rego + AB298(n=15)bAtezo + rego(n=15)aRego (control)(n=19)a,cORR, n (%)1 (6.7)1 (6.7)095% CI(0.2, 32.0)(0.2, 32.0)(0.0, 17.7)CR, n (%)00095% CI(0.0, 21.8)(0.0, 21.8)(0.0, 17.7)PR, n (%)1 (6.7)1 (6.7)095% CI(0.2, 32.0)(0.2, 32.0)(0.00, 17.7)SD, n (%)8 (53.3)5 (33.3)12 (63.2)95% CI(26.6, 78.7)(11.8, 61.6)(38.4, 83.7)PD, n (%)4 (26.7)7 (46.7)5 (26.3)95% CI(7.8, 55.1)(21.3, 73.4)(9.2, 51.2)DCR, n (%)6 (40.0)2 (13.3)3 (15.8)95% CI(16.3, 67.7)(1.7, 40.5)(3.4, 39.6)Median PFS (investigator-assessed RECIST 1.1), mo4.61.82.895% CI(2.6, 5.8)(1.4, 3.0)(2.2, 3.0)HR vs rego (95% CI)0.8 (0.4, 1.6)1.7 (0.8, 3.6)Median OS, mo8.711.010.295% CI(6.6, 14.6)(5.3, 16.7)(4.4, 12.3)HR vs rego (95% CI)0.9 (0.4,..."

Clinical • IO biomarker • Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor • KRAS

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 • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PD-L1

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=151 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Feb 2025 ➔ Aug 2025 | Trial primary completion date: Feb 2025 ➔ Aug 2025

Monotherapy • 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

Arcus Biosciences Reports Fourth-Quarter and Full-Year 2024 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights:...CD73-Adenosine Axis:...(i) Quemliclustat: In the fourth quarter of 2024, Arcus initiated PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer. In February 2025, Arcus’s partner, Taiho, dosed their first patient in Japan for PRISM-1; (ii) Etrumadenant: Arcus plans to meet with the FDA in the first half of 2025 to clarify next steps for ARC-9, evaluating etrumadenant plus zimberelimab, FOLFOX, chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC)."

FDA event • Trial status • Colorectal Cancer • Pancreatic Ductal Adenocarcinoma

Neoadjuvant Atezolizumab-Based Combination Therapy in Men With Localized Prostate Cancer Prior to Radical Prostatectomy (clinicaltrials.gov) - P2 | N=26 | Active, not recruiting | Sponsor: David Oh | Recruiting ➔ Active, not recruiting | N=68 ➔ 26 | Trial completion date: Feb 2025 ➔ Feb 2026 | Trial primary completion date: Feb 2025 ➔ Feb 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

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

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

ARC-4: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer (clinicaltrials.gov) - P1 | N=77 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

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 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Oct 2024 ➔ Jul 2025 | Trial primary completion date: Oct 2024 ➔ Jul 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor