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

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

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 2030 ➔ Dec 2031

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

Remodeling TME via feedback-driven photothermal-ferroptosis-immune cascade. (PubMed, Biomaterials) - "The resulting immunogenic cell death (ICD) promotes dendritic cell maturation and CD8+ T cell infiltration, while AB928 alleviates adenosine-mediated immunosuppression, allowing ICD-driven immunity to be sustained...Experimental results demonstrate that AIF NPs effectively rewires immunologically "cold" TNBC into a responsive "hot" phenotype, achieving over 90% tumor growth inhibition in a 4T1 murine model with minimal systemic toxicity. These findings highlight how feedback-driven coordination of cell death and immunity can be strategically leveraged to address therapeutic bottlenecks in TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • CDC37 • HSP90AA1 • IFNG • SLC7A11

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Arcus Biosciences, Inc.; Initiation date: Jan 2020 ➔ May 2020

Clinical • Combination therapy • Monotherapy • Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • EGFR • 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=150 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Jun 2022 ➔ Feb 2023 | Trial primary completion date: Mar 2022 ➔ Nov 2022

Combination therapy • 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

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Arcus Biosciences, Inc.

Clinical • Combination therapy • Monotherapy • New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • PD-L1

Neoadjuvant Atezolizumab-Based Combination Therapy in Men With Localized Prostate Cancer Prior to Radical Prostatectomy (clinicaltrials.gov) - P2 | N=68 | Recruiting | Sponsor: David Oh | Trial completion date: Apr 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2026 ➔ Apr 2027

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

VELOCITY-Lung: Study of Novel Treatment Combinations in Patients With Lung Cancer (clinicaltrials.gov) - P2 | N=192 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • 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 completion date: Jun 2030 ➔ Dec 2030 | Trial primary completion date: Apr 2026 ➔ Oct 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

Fatty acids in the tumor microenvironment reprogram neutrophils to induce immunosuppression via adenosine. (PubMed, bioRxiv) - "Importantly, AB928 synergized with anti-PD-1 therapy to enhance survival in an autochthonous model of metastatic CRC. Our findings define a metabolic immune evasion mechanism in the TME and provide a rationale for targeting neutrophil-derived adenosine signaling to improve immunotherapy responses in CRC and other solid tumors."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • PPARA

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

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

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

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 • 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

Phase Ib/II, global, open-label, randomized evaluation of atezolizumab (atezo) + etrumadenant (etruma) + chemotherapy (chemo) vs chemo alone in MORPHEUS-PDAC (AACR 2024) - P1/2 | "Etruma, a dual adenosine A2a/A2b receptor antagonist, was evaluated in combination with atezo (anti-programmed death-ligand 1 [PD-L1] antibody) and chemo vs chemo alone (control) in patients (pts) with first-line PDAC in the MORPHEUS-PDAC study (NCT03193190). Pts were randomized to receive atezo (840 mg IV; Days 1 and 15 of 28-day cycles) + etruma (150 mg orally once daily) + chemo (nab-paclitaxel 125 mg/m2 IV and gemcitabine 1000 mg/m2 IV; Days 1, 8 and 15 of 28-day cycles), or chemo alone, until unacceptable toxicity or loss of clinical benefit. In MORPHEUS-PDAC, the ORR primary endpoint was not met although both median PFS and OS were numerically improved with the combination therapy, suggesting that the addition of etruma and atezo may confer a benefit. Overall, atezo + etruma + chemo was tolerable. Safety of the combination was consistent with the known risks of the individual treatments."

Clinical • IO biomarker • P1/2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD73

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