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DRUG:

quemliclustat (AB680)

i
Other names: AB680, AB-680
Associations
Company:
Arcus Biosci, Gilead, Otsuka
Drug class:
CD73 inhibitor
Associations
2ms
Enrollment open
|
oxaliplatin • irinotecan • Yutuo (zimberelimab) • leucovorin calcium • fluorouracil topical • quemliclustat (AB680)
2ms
New P3 trial
|
gemcitabine • albumin-bound paclitaxel • quemliclustat (AB680)
2ms
EDGE-Lung: Study With Immunotherapy Combinations in Participants With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
P2, N=320, Recruiting, Gilead Sciences | Trial completion date: Sep 2026 --> Dec 2027 | Trial primary completion date: Sep 2026 --> Dec 2027
Trial completion date • Trial primary completion date • Metastases
|
docetaxel • Yutuo (zimberelimab) • domvanalimab (AB154) • quemliclustat (AB680)
2ms
ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
P1/2, N=173, Completed, Arcus Biosciences, Inc. | Active, not recruiting --> Completed
Trial completion • Combination therapy • Metastases
|
docetaxel • Xtandi (enzalutamide capsule) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
3ms
Preventive Treatment with a CD73 Small Molecule Inhibitor Enhances Immune Surveillance in K-Ras Mutant Pancreatic Intraepithelial Neoplasia. (PubMed, Cancer Prev Res (Phila))
To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse (GEM) model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression...The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD73 (5'-Nucleotidase Ecto) • CD4 (CD4 Molecule) • NT5E (5'-Nucleotidase Ecto)
|
quemliclustat (AB680)
3ms
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, Arcus Biosciences, Inc. | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jul 2024 --> Oct 2024
Trial completion date • Trial primary completion date • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
4ms
Interference of ATP-Adenosine Axis by Engineered Biohybrid for Amplifying Immunogenic Cell Death-Mediated Antitumor Immunotherapy. (PubMed, Adv Mater)
Specifically, ZIF-90, an ATP-responsive consumer, is synthesized as the core carrier to encapsulate AB680 (CD73 inhibitor) and then coated with an iron-polyphenol layer to prepare the ICD inducer (AZTF), which is further grafted onto prebiotic bacteria via the esterification reaction to obtain the engineered biohybrid (Bc@AZTF). Particularly, the designed Bc@AZTF can actively enrich in tumor sites and respond to the acidic tumor microenvironment to offload AZTF nanoparticles, which can consume intracellular ATP (iATP) content and simultaneously inhibit the ATP-adenosine axis to reduce the accumulation of adenosine, thereby alleviating adenosine-mediated immunosuppression and strikingly amplifying ICD effect. Importantly, the synergy of anti-PD-1 (αPD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism.
Journal
|
CD73 (5'-Nucleotidase Ecto)
|
quemliclustat (AB680)
4ms
Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma. (PubMed, J Cancer Res Clin Oncol)
CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • TNFA (Tumor Necrosis Factor-Alpha) • CD73 (5'-Nucleotidase Ecto) • CD4 (CD4 Molecule) • ICOS (Inducible T Cell Costimulator) • NT5E (5'-Nucleotidase Ecto) • GZMB (Granzyme B) • NICD (NOTCH1 intracellular domain)
|
cisplatin • gemcitabine • quemliclustat (AB680)
6ms
Enrollment open
|
gemcitabine • albumin-bound paclitaxel • Yutuo (zimberelimab) • quemliclustat (AB680)
6ms
Trial primary completion date • Checkpoint inhibition • Metastases
|
Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)
7ms
ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov)
P1, N=165, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Jun 2024 --> May 2027 | Trial primary completion date: Jun 2024 --> May 2027
Trial completion date • Trial primary completion date • Combination therapy
|
CD73 (5'-Nucleotidase Ecto)
|
gemcitabine • albumin-bound paclitaxel • Yutuo (zimberelimab) • quemliclustat (AB680)
8ms
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=360, Recruiting, Arcus Biosciences, Inc. | N=200 --> 360 | Trial completion date: Nov 2025 --> Jun 2027 | Trial primary completion date: Sep 2025 --> Sep 2026
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1)
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5-fluorouracil • oxaliplatin • Yutuo (zimberelimab) • leucovorin calcium • domvanalimab (AB154) • quemliclustat (AB680)
9ms
AIRPanc: Combination Therapy in Patients With Localized Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov)
P2, N=60, Recruiting, Gulam Manji | Initiation date: Oct 2023 --> Jun 2024
Trial initiation date • Combination therapy • Checkpoint inhibition • Checkpoint block • Metastases
|
5-fluorouracil • oxaliplatin • irinotecan • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
9ms
Trial suspension • Combination therapy • Metastases
|
oxaliplatin • irinotecan • Yutuo (zimberelimab) • leucovorin calcium • fluorouracil topical • quemliclustat (AB680)
9ms
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, Arcus Biosciences, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jan 2024 --> Jul 2024 | Trial primary completion date: Jan 2024 --> Jul 2024
Phase classification • Trial completion date • Trial primary completion date • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
9ms
ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
P1/2, N=173, Active, not recruiting, Arcus Biosciences, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Apr 2024 --> Aug 2024 | Trial primary completion date: Apr 2024 --> Aug 2024
Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
docetaxel • Xtandi (enzalutamide capsule) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
11ms
Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (clinicaltrials.gov)
P2, N=39, Recruiting, Nataliya Uboha | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Jun 2024 --> Jan 2025
Trial completion date • Trial primary completion date • Metastases
|
cisplatin • gemcitabine • Yutuo (zimberelimab) • quemliclustat (AB680)
11ms
Enrollment open • Metastases
|
cisplatin • gemcitabine • Yutuo (zimberelimab) • quemliclustat (AB680)
11ms
ARC-8: Phase 1/1b randomized study of quemliclustat + gemcitabine/nab-paclitaxel ± zimberelimab in patients with treatment-naive metastatic pancreatic adenocarcinoma. (ASCO-GI 2024)
Results from ARC-8 demonstrate the addition of Q 100 mg ± Z to G/nP was safe and tolerable, with no significant added toxicity to GnP. Modulation of eADO with Q may confer benefit beyond radiographic measures of disease. The OS is promising and supports further development of Q in mPDAC.
Clinical • P1 data • PD(L)-1 Biomarker • IO biomarker • Metastases
|
CD73 (5'-Nucleotidase Ecto) • NT5E (5'-Nucleotidase Ecto)
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CD73 elevation • CD73 expression
|
gemcitabine • albumin-bound paclitaxel • Yutuo (zimberelimab) • quemliclustat (AB680)
12ms
Tumor Microenvironment Responsive CD8 T Cells and Myeloid-Derived Suppressor Cells to Trigger CD73 Inhibitor AB680-Based Synergistic Therapy for Pancreatic Cancer. (PubMed, Adv Sci (Weinh))
AB680, an exceptionally potent and selective inhibitor of CD73, is administered in an early clinical trial, in conjunction with gemcitabine and anti-PD-1 therapy, for the treatment of PDAC. Finally, the supplementation of a CXCR2 inhibitor is validated to further enhance the therapeutic efficacy when combined with AB680 plus PD-1 inhibitor. These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC.
Journal
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CD8 (cluster of differentiation 8) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
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gemcitabine • quemliclustat (AB680)
1year
ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov)
P1, N=165, Active, not recruiting, Arcus Biosciences, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jun 2024 | Trial primary completion date: Jan 2024 --> Jun 2024
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
|
gemcitabine • albumin-bound paclitaxel • Yutuo (zimberelimab) • quemliclustat (AB680)
1year
Trial primary completion date • Metastases
|
Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
over1year
EDGE-Lung: A Phase 2 Open-Label Platform Study to Evaluate Immunotherapy-Based Combinations in Patients with Metastatic NSCLC (IASLC-WCLC 2023)
Quemliclustat (quemli) is a potent, selective, small molecule inhibitor of CD73...Domvanalimab (dom) is an Fc-silent humanized IgG1 monoclonal antibody (mAb) that blocks T cell Immunoglobulin and ITIM domain (TIGIT), reducing immunosuppression of T/natural killer (NK) cells and promoting antitumor activity. Zimberelimab (zim) is a mAb that binds PD-1 on T/NK cells, preventing PD-L1-mediated immunosuppressive effects and resulting in increased immune-mediated tumor cell death...In substudy C, patients with metastatic NSCLC who have progressed after prior platinum-based chemotherapy and anti-PD-L1 therapy will receive docetaxel (75 mg/m2 IV Q3W) in combination with either quemli (300 mg IV Q3W) or dom (1200 mg IV Q3W) in combination with zim (360 mg IV Q3W)...Other endpoints include disease control rate, progression-free survival, duration of response, overall survival, and pharmacokinetics. EDGE-Lung is currently enrolling patients in Asia-Pacific, Europe, and North America.
Clinical • P2 data • PD(L)-1 Biomarker • IO biomarker • Metastases
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • PD-1 (Programmed cell death 1) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
|
EGFR mutation • ALK mutation
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docetaxel • Yutuo (zimberelimab) • domvanalimab (AB154) • quemliclustat (AB680)
over1year
Enrollment open • Checkpoint inhibition • Metastases
|
Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)
over1year
New P2 trial • Checkpoint inhibition • Metastases
|
Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)
over1year
Preclinical testing of CD73 inhibitor AB680 for pancreatic cancer immunoprevention (AACR 2023)
Inhibiting CD73 restructures TME and reduces PanIN incidence and progression to PDAC. CD73 inhibition may be a candidate immunoprevention strategy in pancreatic cancer.
Preclinical
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KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • KRT19 (Keratin 19)
|
KRAS G12D • KRAS G12 • CD8 positive
|
quemliclustat (AB680)
almost2years
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=200, Recruiting, Arcus Biosciences, Inc. | N=120 --> 200 | Trial completion date: May 2024 --> Nov 2025 | Trial primary completion date: Mar 2024 --> Sep 2025
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
5-fluorouracil • oxaliplatin • Yutuo (zimberelimab) • leucovorin calcium • domvanalimab (AB154) • quemliclustat (AB680)
almost2years
CD73 inhibits cGAS-STING and cooperates with CD39 to promote pancreatic cancer. (PubMed, Cancer Immunol Res)
CD73 expression on human and mouse PDAC tumor cells also protected against DNA damage induced by gemcitabine and irradiation. Moreover, cGAS expression in mouse KPC tumor cells was required for anti-tumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression.
Journal
|
CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1) • NT5E (5'-Nucleotidase Ecto) • CGAS (Cyclic GMP-AMP Synthase) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
|
gemcitabine • quemliclustat (AB680)
2years
Additive effect of CD73 inhibitor in colorectal cancer treatment with CDK4/6 inhibitor through regulation of PD-L1. (PubMed, Cell Mol Gastroenterol Hepatol)
In this study, we demonstrated that a novel combination therapy of AB680 and palbociclib may be advantageous for the treatment of CRC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CCND1 (Cyclin D1)
|
PD-L1 expression
|
Erbitux (cetuximab) • Ibrance (palbociclib) • quemliclustat (AB680)
2years
ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
P1b/2, N=342, Recruiting, Arcus Biosciences, Inc. | N=165 --> 342 | Trial completion date: Oct 2023 --> Dec 2025
Enrollment change • Trial completion date • Combination therapy
|
CAST (Calpastatin)
|
docetaxel • Xtandi (enzalutamide capsule) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
over2years
Role of the extracellular ATP/adenosine pathway in neutrophil-mediated T cell suppression in ovarian cancer microenvironment (IMMUNOLOGY 2022)
CD73 inhibitor Adenosine 5'-(α,β-methylene)diphosphate also abrogated PMN suppressor function while using a different inhibitor (AB-680) had no effect...Together, these studies point to eATP as a modulator of PMN suppressor function in the TME and the potential to abrogate suppression by targeting CD39. Future studies will address the specific signaling functions of eATP on PMN in the TME that drive suppressor function.
IO biomarker
|
ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
quemliclustat (AB680)
over2years
Preclinical testing of CD73 inhibitors for pancreatic cancer immunoprevention (AACR 2022)
We conclude oral gavage delivery of CD73 inhibitor AB680 at 10mg/kg (6x/week) reduces tumor growth in KPC syngeneic tumor bearing mice. Treatment with AB680 at 10mg/kg 3x/week significantly increases tumor doubling time, significantly alters intratumoral immune cell populations, and results in a significant decrease in intratumoral adenosine levels. In addition, we observed a significant increase in infiltration of activated CD8-positive T cells indicating oral gavage delivery using AB680 reverses immunosuppression in vivo.
Preclinical
|
CD8 (cluster of differentiation 8)
|
CD8 positive
|
quemliclustat (AB680)
3years
Immunotherapy Strategy Targeting Programmed Cell Death Ligand 1 and CD73 with Macrophage-Derived Mimetic Nanovesicles to Treat Bladder Cancer. (PubMed, Mol Pharm)
Macrophage-derived exosome-mimetic nanovesicles (EMVs) were designed and validated as a nanoplatform for coloading and delivery of the CD73 inhibitor (AB680) and the monoclonal antibody to programmed cell death ligand 1 (aPDL1)...Moreover, the CD73 inhibitor reduced extracellular adenosine production, and the combination therapy significantly promoted the activation and infiltration of cytotoxic T-lymphocytes, which helped to optimally suppress tumor growth and extend median survival in vivo. Therefore, using EMVs to deliver a combination of aPDL1 and the CD73 inhibitor may be a useful combined immunotherapy strategy for treating bladder cancer.
Journal
|
PD-L1 (Programmed death ligand 1) • CD73 (5'-Nucleotidase Ecto)
|
quemliclustat (AB680)
over3years
Single-cell RNA sequencing reveals distinct cellular factors for response to immunotherapy targeting CD73 and PD-1 in colorectal cancer. (PubMed, J Immunother Cancer)
The intratumoral immunomodulation of CD73 inhibition is distinct from PD-1 inhibition and exhibits potential as a novel anticancer immunotherapy for CRC, possibly through a synergistic effect when combined with PD-1 blocker treatments. This study may contribute to the ongoing development of anticancer immunotherapies targeting refractory CRC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD73 (5'-Nucleotidase Ecto) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • MALAT1 (Metastasis associated lung adenocarcinoma transcript 1) • NT5E (5'-Nucleotidase Ecto) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
|
CD73 expression
|
Keytruda (pembrolizumab) • Opdivo (nivolumab) • Tecentriq (atezolizumab) • quemliclustat (AB680)
over4years
[VIRTUAL] ARC-6: A phase Ib/II, open-label, randomized platform study evaluating the efficacy and safety of AB928-based treatment combinations in patients with metastatic castrate resistant prostate cancer (ESMO 2020)
Treatment arms will independently evaluate AB928 + zimberelimab (AB122; anti-PD-1 antibody) alone or in combination with an SOC backbone (enzalutamide or docetaxel) in earlier-line pts or AB928 + AB680 (CD73 inhibitor) +/- zimberelimab in later-line pts. Funding: Arcus Biosciences. Clinical trial identification: NCT04381832.
Clinical • P1/2 data
|
CD73 (5'-Nucleotidase Ecto) • KLK3 (Kallikrein-related peptidase 3)
|
docetaxel • Xtandi (enzalutamide capsule) • Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)
over4years
An Exceptionally Potent Inhibitor of Human CD73. (PubMed, Biochemistry)
We found AB680 to be a reversible, slow-onset competitive inhibitor of human CD73 with a K of 5 pM. Clinical candidates of this potency are uncommon and deserve special consideration during lead optimization.
Journal
|
CD73 (5'-Nucleotidase Ecto)
|
quemliclustat (AB680)
almost5years
A phase Ib/II, open-label, platform study evaluating the efficacy and safety of AB928-based treatment combinations in participants with metastatic castrate-resistant prostate cancer. (ASCO-GU 2020)
Each cohort will independently assess AB928 plus AB122 (anti-PD-1 antibody) in combination with standard of care (SOC; enzalutamide, docetaxel) or AB928 plus AB680 (CD73 inhibitor) with or without AB122. This Ph1b/2 study is the first to target the adenosine axis using a dual A2aR/A2bR antagonist (AB928) together with a small molecule CD73 inhibitor (AB680), anti-PD-1 antibody (AB122), and SOC for mCRPC. Study enrollment is proceeding in the United States; results will be shared in upcoming scientific conferences. Research Funding: Arcus Biosciences.
Clinical • P1/2 data
|
KLK3 (Kallikrein-related peptidase 3)
|
docetaxel • Xtandi (enzalutamide capsule) • Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)
almost5years
A phase Ib/II, open-label, platform study evaluating the efficacy and safety of AB928-based treatment combinations in participants with metastatic castrate-resistant prostate cancer. (ASCO-GU 2020)
Each cohort will independently assess AB928 plus AB122 (anti-PD-1 antibody) in combination with standard of care (SOC; enzalutamide, docetaxel) or AB928 plus AB680 (CD73 inhibitor) with or without AB122. This Ph1b/2 study is the first to target the adenosine axis using a dual A2aR/A2bR antagonist (AB928) together with a small molecule CD73 inhibitor (AB680), anti-PD-1 antibody (AB122), and SOC for mCRPC. Study enrollment is proceeding in the United States; results will be shared in upcoming scientific conferences. Research Funding: Arcus Biosciences.
Clinical • P1/2 data
|
KLK3 (Kallikrein-related peptidase 3)
|
docetaxel • Xtandi (enzalutamide capsule) • Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)