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

ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov) - P1 | N=196 | Completed | Sponsor: Arcus Biosciences, Inc. | Trial completion date: May 2027 ➔ Jul 2026 | Trial primary completion date: May 2027 ➔ Jul 2026 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer (clinicaltrials.gov) - P1/2 | N=27 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

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

Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC) (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Nataliya Uboha | Trial primary completion date: Jul 2026 ➔ Dec 2026

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

Planned Data Readouts (Businesswire) - "Enrollment was completed in September 2025 for PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma. Results from this study are expected in the first half of 2027."

P3 data • Pancreatic Ductal Adenocarcinoma

Celastrol Ameliorates Systemic Lupus Erythematosus via Restoring Nt5e/ adenosine-dependent Th17/Treg Balance. (PubMed, Phytomedicine) - "Our results indicate that Cel restores the Th17/Treg balance via upregulating Nt5e, thereby ameliorating SLE-associated injury. This study thus provides novel insights into the mechanism of Cel treating SLE and underscores the therapeutic potential of targeting Nt5e in SLE."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Ophthalmology • Systemic Lupus Erythematosus • CD73 • FOXP3 • NT5E

Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC) (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Nataliya Uboha | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jan 2026 ➔ Jul 2026

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

Enfortumab Vedotin, Pembrolizumab and Quemliclustat for the Treatment of Unresectable Locally Advanced and Metastatic Urothelial Cancer (clinicaltrials.gov) - P1/2 | N=27 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center

New P1/2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Benchmarking survival outcomes of quemliclustat in first-line metastatic pancreatic ductal adenocarcinoma: Insights from ARC-8 and implications for PRISM-1. (ASCO 2026) - "In a trial-in-context benchmark analysis, quemliclustat-based regimens in ARC-8 were associated with a consistent OS advantage compared with contemporary GnP benchmarks despite similar PFS and ORR, suggesting a clinically meaningful survival signal and supporting the clinical and biologic rationale for the ongoing phase III PRISM-1 trial. OS, PFS and ORR for ARC-8 Quemliclustat regimens v/s GnP benchmarks Q=quemliclustat; Z=zimberelimab; GnP=gemcitabine+nab-paclitaxel."

Clinical • Metastases • Oncology • Pancreatic Ductal Adenocarcinoma • CD73

Quemliclustat: "Phase 1 study showed 5.9 month mOS improvement vs G/nP"; Pancreatic cancer (Arcus Biosciences) - Q1 2026 Results

P1 data • Oncology • Pancreatic Cancer

Metabolism, Excretion, and Mass Balance Study of Quemliclustat in Healthy Adult Participants (ARC-24) (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion

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

Planned Data Readouts: Quemliclustat (small-molecule CD73 inhibitor) (Arcus Biosciences Press Release)

Enrollment closed • P3 data • Pancreatic Ductal Adenocarcinoma

CBO421: A novel drug Fc-conjugate to prevent tumor immune evasion via the CD73/adenosine pathway (AACR 2024) - "In vivo efficacy of CBO421 monotherapy was evaluated in a syngeneic mouse model.Results CBO421 exhibited a binding affinity to human CD73 (KD = 0.8 nM) that was comparable to or greater to the affinity observed with small molecule inhibitors (AB680, OP-5244) and CD73-targeting mAbs (oleclumab, mupadolimab biosimilars). CBO421 demonstrated high potency in functional cell-based assays and robust antitumor efficacy in a syngeneic mouse model. Currently, CBO421 is being advanced as a clinical development candidate for the treatment of solid cancers."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • CD73 • CD8 • NT5E

Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial. (PubMed, Nat Med) - P1 | "In a phase 1b trial (ARC-8), we evaluated safety and efficacy of quemliclustat combined with gemcitabine/nab-paclitaxel (G/nP) with or without zimberelimab (anti-programmed cell death protein 1 (PD-1)) in first-line metastatic pancreatic ductal adenocarcinoma (PDAC)...High tumor NR4A expression was associated with improved overall survival (OS) in ARC-8 but not in two external cohorts from the PRINCE (G/nP + nivolumab (nivo)) or Morpheus-PDAC (G/nP) trials...In paired pretreatment/posttreatment biopsies, maximal downregulation of NR4A expression was associated with T cell activation and improved OS, pointing to a biological link between tumor adenosine and clinical benefit. ClinicalTrials.gov identifier: NCT04104672 ."

IO biomarker • Journal • P1 data • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD73 • NR4A1

CBO421, a novel drug Fc-conjugate, inhibits the enzymatic activity of CD73 and triggers CD73 internalization (AACR 2024) - "CD73 inhibition by CBO421 of soluble CD73 or CD73 expressed on the surface of the MDA-MB-231 cell line was comparable or superior to AB680 or oleclumab. Receptor internalization activities of CBO421 and oleclumab were compared. CBO421 and oleclumab internalization percentages were determined at 1 h (52.3% vs 26.7%), 4 h (80.8% vs 38.0%), and 6 h (84.8% vs 42.9%) respectively, with CBO421 demonstrating superior maximal receptor internalization."

Late-breaking abstract • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD73 • CD8 • NT5E

Metabolism, Excretion, and Mass Balance Study of Quemliclustat in Healthy Adult Participants (ARC-24) (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed

Metabolism, Excretion, and Mass Balance Study of Quemliclustat in Healthy Adult Participants (ARC-24) (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Metabolism, Excretion, and Mass Balance Study of Quemliclustat in Healthy Adult Participants (ARC-24) (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Arcus Biosciences, Inc.

New P1 trial

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: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

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

Potent Competitive Inhibitors of Ecto-5'-nucleotidase (CD73) based on 6‑(Het)aryl-7-deazapurine Ribonucleoside 5'‑O‑Bisphosphonates. (PubMed, ACS Pharmacol Transl Sci) - "They effectively suppressed adenosine formation in MDA-MB-231 cells, rescued CD8+ T cell activation, and were nontoxic to human fibroblasts. Overall, their profile compares favorably with AB680, a CD73 inhibitor currently in phase I/II clinical trials."

Journal • Oncology • CD73 • CD8 • ENTPD1

Quemliclustat (CD73 inhibitor for pancreatic cancer) (Businesswire) - "Arcus's oncology portfolio also includes quemliclustat, a small-molecule CD73 inhibitor, which is being evaluated in PRISM-1, a registrational Phase 3 study in 1L pancreatic cancer that completed enrollment in September 2025. Results from this study are expected in the first half of 2027."

P3 data • Pancreatic Ductal Adenocarcinoma

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