quemliclustat (AB680) / Arcus Biosci, Gilead, Otsuka - LARVOL DELTA

Arcus's oncology portfolio also includes quemliclustat, a small-molecule CD73 inhibitor that completed enrollment of PRISM-1, the Phase 3 study in pancreatic cancer, earlier this year. (Arcus Biosciences Press Release) - "Results are expected in 2027 for the registrational study, which is evaluating quemliclustat plus gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma."

P3 data • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

The interaction of AB-680, a CD73 inhibitor, with NBTI, a nucleoside transporter inhibitor, on the adenosinergic control of atrial contractility. (PubMed, Front Pharmacol) - "We also found that DMSO interfered with our measurements to a lesser extent than the buffer recommended for in vivo studies. In addition, AB-680, when co-administered with NBTI (both dissolved in DMSO), reduced cx (i.e. probably also the surplus interstitial adenosine) by at least half."

Journal • CD73

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

Quemliclustat (small-molecule CD73 inhibitor) (Businesswire) - "Enrollment has been completed for PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in 1L metastatic pancreatic ductal adenocarcinoma, within 12 months of study initiation."

Enrollment closed • Pancreatic Ductal Adenocarcinoma

EDGE-Lung: Study With Various Immunotherapy Treatments in Participants With Lung Cancer (clinicaltrials.gov) - P2 | N=400 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

PRISM-1: Study of Quemliclustat and Chemotherapy Versus Placebo and Chemotherapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P3 | N=610 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

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

Arcus Biosciences Reports Second-Quarter 2025 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights:...Quemliclustat (small-molecule CD73 inhibitor):...PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma, is enrolling rapidly, with enrollment completion expected in the third quarter of 2025, well within 12 months of study initiation."

Enrollment status • Pancreatic Ductal Adenocarcinoma

Quemliclustat: Completion of P3 PRISM-1 trial (NCT06608927) for metastatic pancreatic ductal adenocarcinoma in Nov 2030 (Otsuka) - Q2 FY2025 Results

Trial completion date • Oncology • Pancreatic Ductal Adenocarcinoma

Quemliclustat and chemotherapy in previously untreated patients with metastatic pancreatic ductal adenocarcinoma: PRISM-1, a randomized, placebo-controlled, phase III trial (ESMO-GI 2025) - P3 | "In a previous phase 1b study (ARC-8), quemliclustat combined with nab-paclitaxel (nP) plus gemcitabine (Gem) demonstrated a promising signal in median OS without a significant increase in toxicity.Trial design: PRISM-1 is a randomized, placebo-controlled, double-blind, global, multicenter, phase 3 trial evaluating the efficacy and safety of quemliclustat in treatment-naive patients with metastatic PDAC. The safety and tolerability of quemliclustat in combination with nP-Gem will be assessed; adverse events will be graded according to NCI CTCAE 5.0. Recruitment is planned across Asia, Australia, Europe, and North America."

Clinical • Metastases • P3 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD73 • NT5E

Arcus Biosciences’ Quemliclustat Receives Orphan Drug Designation for Pancreatic Cancer (Businesswire) - "Arcus Biosciences...announced that quemliclustat, an investigational small molecule CD73 inhibitor, was granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of pancreatic cancer....The company initiated PRISM-1, a registrational Phase 3 study to evaluate quemliclustat plus gemcitabine/nab-paclitaxel chemotherapy versus gemcitabine/nab-paclitaxel chemotherapy alone in approximately 610 patients with pancreatic ductal adenocarcinoma (PDAC) that have not been previously treated in the metastatic setting. The study is expected to be fully enrolled this year."

Enrollment status • Orphan drug • Pancreatic Ductal Adenocarcinoma

CD73 inhibitor AB680 suppresses glioblastoma in mice by inhibiting purine metabolism and promoting P2RY12+ microglia transformation. (PubMed, Acta Pharmacol Sin) - "Overall, this study demonstrates that targeting CD73 with AB680 alters purine metabolism in the GBM microenvironment, promotes the transformation of P2RY12+ microglia, and triggers robust anti-tumor immune responses. These results support the rationale for AB680-based therapeutic clinical trials for GBM."

Journal • Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD73 • NT5E

CD73 inhibitor AB680 suppresses glioblastoma in mice by inhibiting purine metabolism and promoting P2RY12+ microglia transformation (Nature, Acta Pharmacol Sin) - "Administration of AB680 significantly prolonged survival in G422TN-GBM-bearing mice, reduced tumor size, cell proliferation, angiogenesis, and enhanced microglia activation and anti-tumor immune responses....Furthermore, AB680 combined with RT/TMZ exhibited synergistic therapeutic effects by reversing RT/TMZ-induced increases in adenosine levels and promoting the transformation of P2RY12+ microglia."

Preclinical • Glioblastoma

CD73 inhibitor AB680 suppresses glioblastoma in mice by inhibiting purine metabolism and promoting P2RY12+ microglia transformation (Nature, Acta Pharmacol Sin) - "Administration of AB680 significantly prolonged survival in G422TN-GBM-bearing mice, reduced tumor size, cell proliferation, angiogenesis, and enhanced microglia activation and anti-tumor immune responses....Furthermore, AB680 combined with RT/TMZ exhibited synergistic therapeutic effects by reversing RT/TMZ-induced increases in adenosine levels and promoting the transformation of P2RY12+ microglia."

Preclinical • Glioblastoma

EDGE-Gastric: A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies (clinicaltrials.gov) - P2 | N=332 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial primary completion date: Sep 2026 ➔ Jan 2027

IO biomarker • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Disorder • Oncology • PD-L1

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

ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov) - P1 | N=195 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Arcus Biosciences Reports First-Quarter 2025 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights:...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 first-line treatment of metastatic pancreatic cancer. PRISM-1 is recruiting rapidly, with enrollment completion expected by the end of 2025."

Trial status • Pancreatic Cancer

Zimberelimab and Quemliclustat in Combination With Chemotherapy for the Treatment of Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=56 | Recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Sep 2026 ➔ Mar 2026 | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Adenosine production suppression and PD-1 immune check point inhibitor for treatment of malignant pleural mesothelioma. (MPM) (AACR 2025) - "After three weeks we started monitoring tumor growth and the animals were randomized into five groups of three mice each for treatment with PBS 100 μl (control), Pembro (anti murine PD-1; MCE ) 4.4 mg/Kg, TT-4 (ADORA2 Inhibitor Portage), 3 mg/Kg, Pembro+TT-4, AB-680 (CD73 inhibitor, MCE, HY-125286) 20 mg kg) and Pembro+AB-680 were injected every two days for three weeks. Inhibition of the purinergic pathway exerts a significant immune-mediated MPM growth inhibition"

IO biomarker • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • ADORA2A • ADORA2B • CD73 • CD8 • ENTPD1

Zimberelimab and Quemliclustat in Combination With Chemotherapy for the Treatment of Patients With Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=56 | Recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: May 2026 ➔ Sep 2026 | Trial primary completion date: May 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

The adenosine pathway is an actionable multitarget for mesothelioma (MMe) (ELCC 2025) - "Inhibition of the purinergic pathway exerts significant immune-mediated growth inhibition vs MPM."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • ADORA2B • CD73 • ENTPD1

EDGE-Gastric: A Safety and Efficacy Study of Treatment Combinations With and Without Chemotherapy in Adult Participants With Advanced Upper Gastrointestinal Tract Malignancies (clinicaltrials.gov) - P2 | N=333 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • 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

Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC) (clinicaltrials.gov) - P2 | N=39 | Recruiting | Sponsor: Nataliya Uboha | Trial completion date: Jul 2025 ➔ Jul 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Hepatology • Oncology • Solid Tumor