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

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

The adenosine receptor antagonist etrumadenant reduces tumor adenosine-regulated NR4A gene expression and increases mCRC inflammation in patients from the ARC-9 trial (SITC 2024) - P1/2 | "Etruma, in combination with zimberelimab (Z) (anti-PD-1 antibody), FOLFOX, and bevacizumab (bev) (EZFB regimen) demonstrated an impressive overall survival (OS) benefit compared to the regorafenib (rego) control arm in third-line, chemo-resistant mCRC in the primary analysis of the ARC-9 study (NCT04660812)...Consistent with an adenosine-targeting MoA, EZFB provided significantly improved PFS and OS compared to rego for patients with CD73 IHC-positive tumors. Ethics Approval All patients were provided the most recent copy of the Informed Consent form describing the study and associated interventions, which the patient or their legally authorized representative were required to sign and date prior to participating in the study."

Clinical • IO biomarker • Colorectal Cancer • Oncology • CD73 • NR4A1 • NR4A2 • NR4A3 • NT5E

CD73-Adenosine Axis: Quemliclustat (small-molecule CD73 inhibitor) and Etrumadenant (A2a/A2b receptor antagonist) (Businesswire) - "Quemliclustat: Arcus has initiated PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer....Etrumadenant: Biomarker data from cohort B of ARC-9, a randomized Phase 1b/2 study evaluating etrumadenant plus zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC), are being presented at SITC in November."

Biomarker • P1/2 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Arcus Biosciences to Present New Data for Anti-TIGIT Domvanalimab Plus Zimberelimab at the Society for Immunotherapy of Cancer Annual Meeting (Businesswire) - "A late-breaking poster presented by Melissa L. Johnson, M.D., director, lung cancer research, Sarah Cannon Research Institute, will highlight safety and efficacy data, including objective response rate, progression-free survival and overall survival from ARC-10. This study is a randomized, open-label, three-arm study evaluating domvanalimab, an Fc-silent anti-TIGIT monoclonal antibody, plus zimberelimab, an anti-PD-1 monoclonal antibody, versus zimberelimab or chemotherapy, in patients with front-line locally advanced or metastatic squamous or non-squamous NSCLC with a PD-L1 tumor proportion score of ≥50% without the presence of any tumor genomic aberration or driver mutation for which a targeted therapy is approved."

Clinical data • Late-breaking abstract • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=173 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

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 completion date: Dec 2027 ➔ Dec 2030

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

ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC) (DAVA Oncology)

CME

VELOCITY-Lung: Study of Novel Treatment Combinations in Patients With Lung Cancer (clinicaltrials.gov) - P2 | N=593 | Recruiting | Sponsor: Gilead Sciences | N=397 ➔ 593

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

Arcus Biosciences Reports Second-Quarter 2024 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights:...(i) Etrumadenant: Biomarker data from...ARC-9...study are expected to be presented at a scientific conference in the second half of 2024;...(ii) Quemliclustat: Initiation of a Phase 3 trial, PRISM-1, of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer is expected to begin by early 2025;...(iii) Early Clinical Programs: Dose escalation for AB801, a potent and highly selective small-molecule AXL inhibitor, continues. Arcus anticipates advancing this molecule into expansion cohorts in NSCLC in early 2025."

Biomarker • New P3 trial • P1/2 data • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

ARC-4: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer (clinicaltrials.gov) - P1 | N=77 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Aug 2024 ➔ Nov 2024 | Trial primary completion date: Aug 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • 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: Jul 2024 ➔ Oct 2024 | Trial primary completion date: Jul 2024 ➔ Oct 2024

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

Etrumadenant: “EZFB demonstrated statistically significant improvement in PFS vs Rego"; Colorectal cancer (Arcus Biosciences) - ASCO 2024: “EZFB demonstrated significant improvement in OS vs Rego”

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology

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

Gilead and Arcus Announce Etrumadenant Plus Zimberelimab Regimen Significantly Reduced the Risk of Death in Third-line Metastatic Colorectal Cancer (Businesswire) - P1b/2 | N=227 | ARC-9 (NCT04660812) | Sponsor: Arcus Biosciences, Inc. | "Gilead Sciences...and Arcus Biosciences...announced new data from Cohort B of ARC-9, a Phase 1b/2 study evaluating the safety and efficacy of etrumadenant...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...ASCO Annual Meeting....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%)."

P1/2 data • Colorectal Cancer