A Phase Ib/II Study to Evaluate the Safety and Efficacy of Enfortumab Vedotin Plus Pembrolizumab in Combination With Quemliclustat in Unresectable Locally Advanced and Metastatic Urothelial Carcinoma

This phase Ib/II trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Quemliclustat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving quemliclustat in combination with enfortumab vedotin and pembrolizumab and may be safe, tolerable and/or effective in treating patients with unresectable locally advanced and metastatic urothelial cancer.

Start Date15 Oct 2026

Sponsor / Collaborator

Fred Hutchinson Cancer Center

[+1]

NCT07364214

/ CompletedPhase 1

A Phase 1, Open-Label Study to Characterize the Metabolism, Excretion, and Mass Balance of a Single Intravenous Dose of 100 mg Containing 75 µCi of [14C]-Quemliclustat in Healthy Adult Male Participants

The purpose of the study is to investigate the routes of elimination and overall mass balance of 100 mg quemliclustat containing 75 μCi [14C] following a single IV infusion of [14C]-quemliclustat in healthy adult male participants, and to quantify total radioactivity (TRA) in plasma, whole blood, urine, and feces.

Start Date03 Feb 2026

Sponsor / Collaborator

Arcus Biosciences, Inc.

JPRN-jRCT2051250013

/ RecruitingPhase 1

Platform Study of Zipalertinib in Patients with EGFR-mutant NSCLC (REZILIENT5 study)

Start Date08 May 2025

Sponsor / Collaborator

Taiho Pharmaceutical Co., Ltd.

100 Clinical Results associated with Quemliclustat

100 Translational Medicine associated with Quemliclustat

100 Patents (Medical) associated with Quemliclustat

Literatures (Medical) associated with Quemliclustat

01 Oct 2026·PHYTOMEDICINE

Celastrol Ameliorates Systemic Lupus Erythematosus via Restoring Nt5e/ adenosine-dependent Th17/Treg Balance

Article

Author: Li, Yiping ; Zheng, Yingying ; Xu, Danna ; Wen, Chengping ; Wang, Chenxi ; Li, Suling ; Pang, Zhengyi ; Huang, Lin ; Zhang, Yun ; Jiang, Zhangsheng ; He, Zhixing

BACKGROUND:

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the breakdown of immune tolerance, systemic inflammation, and multi-organ damage. The imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells is a key driver in SLE pathogenesis.

PURPOSE:

This study aimed to investigate whether Celastrol (Cel), a natural triterpenoid derived from Tripterygium wilfordii, exerts therapeutic effects in SLE by modulating the Th17/Treg balance, and to explore the underlying molecular mechanism.

STUDY DESIGN:

An in vivo study using the MRL/lpr lupus-prone mouse model was conducted to evaluate therapeutic efficacy, complemented by in vitro assays and molecular analysis to identify target pathways.

METHODS:

MRL/lpr mice were orally administered Cel and disease progression was assessed via survival analysis, spleen pathology, autoantibody levels, and renal histopathology. T cell subsets were analyzed using flow cytometry and Western blot. Proteomic profiling was performed to identify potential molecular targets, followed by molecular docking, molecular dynamics simulations, cellular thermal shift assay (CETSA), MicroScale Thermophoresis (MST) and surface plasmon resonance (SPR) to validate target engagement. AB680, a pharmacological inhibitor of ecto-5'-nucleotidase (Nt5e), was used to confirm the functional role of Nt5e.

RESULTS:

Cel treatment significantly improved survival, reduced splenomegaly, suppressed anti-dsDNA/ANA autoantibody levels, and alleviated renal damage in lupus-prone mice. It promoted Treg cell differentiation and inhibited Th17 polarization, evidenced by increased Foxp3 expression and decreased STAT3 phosphorylation. Nt5e was identified as a direct binding target of Cel. Target engagement was validated through CETSA, MST and SPR, and inhibition of Nt5e by AB680 partially reversed Cel's therapeutic effects, indicating that Nt5e mediates its immunomodulatory action.

CONCLUSION:

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.

01 Apr 2026·NATURE MEDICINE

Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial

Article

Author: DiRenzo, Daniel M ; Ulahannan, Susanna V ; Wang, Ning ; Walters, Matthew J ; Wainberg, Zev A ; Manji, Gulam A ; Scott, Jennifer R ; Mrouj, Karim ; Oberstein, Paul E ; Beagle, Brandon ; Kaplan, Angelo ; Pant, Shubham ; Wu, Wilson ; Weeder, Ben ; Spigel, David R ; Cho, Soonweng ; O'Reilly, Eileen M ; Bahary, Nathan ; Shitole, Shravani ; Saeed, Anwaar ; Uboha, Nataliya V ; Kabbarah, Omar ; Ensign, Lisa G ; Kim, Ji Yun

Abstract:

Quemliclustat potently inhibits CD73, a key enzyme producing immunosuppressive adenosine. 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). During the dose-escalation phase, 22 patients were enrolled across five dose levels of quemliclustat (25 mg, 50 mg, 75 mg, 100 mg or 125 mg) with G/nP + zimberelimab. During the dose-expansion phase, 116 patients were enrolled, beginning with a single-arm, non-randomized cohort receiving quemliclustat 100 mg + G/nP + zimberelimab, followed by a randomized cohort in which patients were assigned in a 2:1 ratio to receive quemliclustat 100 mg + G/nP with or without zimberelimab. The primary endpoint was safety and tolerability; secondary endpoints included assessments of clinical activity and survival. In all treatment arms, the safety profile was consistent with that of G/nP. Clinical response rates and survival outcomes were encouraging. NR4A family gene expression was upregulated by adenosine in vitro and by chemotherapy in human PDACs. 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. Spatial tissue analyses revealed a scarcity of activated T cells near regions with high NR4A1 expression, consistent with an immunosuppressed tumor microenvironment. 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 .

09 Jan 2026·ACS Pharmacology & Translational Science

Potent Competitive Inhibitors of Ecto-5′-nucleotidase (CD73) based on 6-(Het)aryl-7-deazapurine Ribonucleoside 5′- O -Bisphosphonates

Article

Author: Konvalinka, Jan ; Poštová Slavětínská, Lenka ; Lepšík, Martin ; Šácha, Pavel ; Hocek, Michal ; Blažková, Kristýna ; Šinkevičiu̅tė, Ugnė ; Řezáč, Jan ; Staník, Radek ; Šímová, Magdalena ; Tichý, Michal ; Ormsby, Tereza

CD73 generates immunosuppressive adenosine in the tumor microenvironment and is a promising target for cancer immunotherapy. We have designed and systematically studied diverse 2-substituted 7-deazapurine ribonucleoside 5'-O-bisphosphonates bearing a variety of (het)-aryl groups at position 6 and discovered their highly potent and selective CD73 inhibition activity. The most active compounds (with single-digit picomolar K _i) contained bicyclic (het)-aryl groups at position 6 in combination with chlorine at position 2. Further optimization of pharmacokinetic properties identified inhibitors with low clearance, long half-life, high solubility, and excellent selectivity over CD39 and NTPDase3. 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.

News (Medical) associated with Quemliclustat

09 Sep 2026

·www.biospace.com

Arcus Biosciences Announces New Employment Inducement Grants - September 9, 2026

HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer and inflammatory and autoimmune diseases, today announced that the Compensation Committee of the Company’s Board of Directors granted one new employee options to purchase a total of 26,350 shares of the Company’s common stock at an exercise price per share of $29.06, which was the closing price on September 8, 2026, and restricted stock units to acquire a total of 13,200 shares of the Company’s common stock. The equity awards were granted pursuant to the Company’s 2020 Inducement Plan, which was approved by the Company’s Board of Directors in January 2020 pursuant to the “inducement exception” under NYSE Listed Company Manual Rule 303A.08. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules for the treatment of cancer and inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of its late-stage portfolio of first- and/or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including casdatifan, a HIF-2α inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . Inducement PR Source: Arcus Biosciences Contacts Investor Inquiries: Pia Eaves VP of Investor Relations & Strategy (617) 459-2006 peaves@arcusbio.com Media Inquiries: Holli Kolkey VP of Corporate Affairs (650) 922-1269 hkolkey@arcusbio.com Maryam Bassiri Director of Corporate Affairs (510) 406-8520 mbassiri@arcusbio.com

26 Aug 2026

·www.biospace.com

Arcus Biosciences to Participate in Three Upcoming Investor Conferences

HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer and inflammatory and autoimmune diseases, announced that its management team will participate in the following upcoming investor conferences in September: Citi’s 2026 Biotech Back to School Conference Date: Wednesday, September 9 th , 2026 Location: New York, NY Format: Fireside chat & 1x1 meetings Time: 10:40 a.m. ET Cantor Fitzgerald Global Healthcare Conference 2026 Date: Thursday, September 10 th , 2026 Location: New York, NY Format: Fireside chat & 1x1 meetings Time: 9:45 a.m. ET Morgan Stanley 24 th Annual Global Healthcare Conference Date: Tuesday, September 15 th , 2026 Location: New York, NY Format: Fireside chat & 1x1 meetings Time: 12:20 p.m. ET Live webcasts of the fireside chats will be available by visiting the “Investors & Media” section of the Arcus Biosciences website at . Replays will be available following the live event. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules for the treatment of cancer and inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of its late-stage portfolio of first- and/or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including casdatifan, a HIF-2α inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . Contacts Investor Inquiries Pia Eaves VP of Investor Relations & Strategy (617) 459-2006 peaves@arcusbio.com Media Inquiries Holli Kolkey VP of Corporate Affairs (650) 922-1269 hkolkey@arcusbio.com Maryam Bassiri Director, Corporate Affairs (510) 406-8520 mbassiri@arcusbio.com

11 Aug 2026

·www.biospace.com

Arcus Biosciences Announces New Employment Inducement Grants - August 11, 2026

HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer and inflammatory and autoimmune diseases, today announced that the Compensation Committee of the Company’s Board of Directors granted one new employee options to purchase a total of 2,850 shares of the Company’s common stock at an exercise price per share of $28.72, which was the closing price on August 10, 2026, and restricted stock units to acquire a total of 1,450 shares of the Company’s common stock. The equity awards were granted pursuant to the Company’s 2020 Inducement Plan, which was approved by the Company’s Board of Directors in January 2020 pursuant to the “inducement exception” under NYSE Listed Company Manual Rule 303A.08. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules for the treatment of cancer and inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of its late-stage portfolio of first- and/or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including casdatifan, a HIF-2α inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . Inducement PR ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Source: Arcus Biosciences Contacts Investor Inquiries: Pia Eaves VP of Investor Relations & Strategy (617) 459-2006 peaves@arcusbio.com Media Inquiries: Holli Kolkey VP of Corporate Affairs (650) 922-1269 hkolkey@arcusbio.com Maryam Bassiri Director of Corporate Affairs (510) 406-8520 mbassiri@arcusbio.com

100 Deals associated with Quemliclustat

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KEGG	Wiki	ATC	Drug Bank
D12373	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	United States	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Japan	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Australia	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Austria	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Belgium	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Canada	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Czechia	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	France	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Germany	Arcus Biosciences, Inc.	13 Dec 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 3	Italy	Arcus Biosciences, Inc.	13 Dec 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARC-8 (ASCO2026)	Phase 1	Metastatic Pancreatic Ductal Adenocarcinoma First line	122	quemliclustat + GnP or quemliclustat + zimberelimab + GnP	lneiwypqmd(omegaomhba) = krwoefgagz xwrpmhhaqf (bmlrwbttzc ) View more	Positive	29 May 2026
				GnP	lneiwypqmd(omegaomhba) = eurhhdqtyb xwrpmhhaqf (bmlrwbttzc ) View more
NCT04104672 (ARC-8, ASCO_GI2024) Manual	Phase 1	Pancreatic adenocarcinoma metastatic First line NT5E	122	quemliclustat+gemcitabine/nab-paclitaxel	zkqvhgjesf(znfmgstxoo) = lfnxhuhnwc bgdlvsqemp (kohflntoua, 24 - 61) View more	Positive	18 Jan 2024
				quemliclustat+gemcitabine/nab-paclitaxel+zimberelimab	zkqvhgjesf(znfmgstxoo) = ktswdmhkxh bgdlvsqemp (kohflntoua, 28 - 48) View more
NCT04104672 (ASCO_GI 12021 \| ASCO_GI 22021) Manual	Phase 1	Pancreatic adenocarcinoma metastatic First line	13	overall	jdgcxglvho(vrtfazizfy) = zttvbydpkp icmhhxowtk (floqjlzcis ) View more	Positive	20 Jan 2021
				chemotherapy+zimberelimab+AB680 (Cohort 1 (25 mg AB680))	zmjnbzfcjh(fyzfhprqmw) = qcukycabjd rrqwwzpwbx (hgqxcttsqa ) View more
NCT04104672 (Corporate Publications) Manual	Phase 1	Metastatic Pancreatic Cancer First line	19	Gemcitabine+Albumin-Bound Paclitaxel+Zimberelimab+AB680	qgplmgtdmq(zmoiqfkwmx) = fatigue (68%), anemia (53%), alopecia (42%), diarrhea (42%) and neutrophil count decrease (42%) wrkvyvtmrl (ipuvctbhee ) View more	Positive	15 Jan 2021
NCT03677973 (Pubmed \| Biochemistry)	Phase 1	-	-	AB680	fzegwremmx(crzucrtdol) = gvmwhbwvld zjdbhcemth (tlkaxixvsn )	-	06 Aug 2019

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