An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer.

Sponsor

Arcus Biosciences, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04660812

Collaborator

(none)

247

Enrollment

Locations

Arms

31.3

Anticipated Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase 1b/2 open-label study will evaluate the antitumour activity and safety of etrumadenant (AB928) treatment combinations in participants with metastatic colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: etrumadenant Drug: zimberelimab Drug: mFOLFOX-6 regimen Drug: bevacizumab Drug: regorafenib Drug: AB680	Phase 1/Phase 2

Detailed Description

This is a multicenter, open-label Phase 1b/2 study in participants with metastatic colorectal cancer that will assess the antitumour activity and safety of etrumadenant.

Approximately 250 participants will be enrolled to 1 of 3 cohorts:

Cohort A) etrumadenant + zimberelimab +mFOLFOX-6 +/-bevacizumab vs mFOLFOX-6 +/-bevacizumab

Cohort B) etrumadenant + zimberelimab +mFOLFOX-6 +/-bevacizumab vs regorafenib

Cohort C) chemotherapy-free combinations of etrumadenant + zimberelimab + other agents

The primary objective of this clinical study is to evaluate the safety of etrumadenant-based combination therapy in participants with metastatic colorectal cancer.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

247 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating The Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer

Actual Study Start Date :

May 10, 2021

Anticipated Primary Completion Date :

Sep 20, 2023

Anticipated Study Completion Date :

Dec 18, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: etrumadenant + zimberelimab + mFOLFOX-6 +/- bevacizumab Participants will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion.	Drug: etrumadenant Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist Other Names: AB928 Drug: zimberelimab Zimberelimab is a fully human anti-PD-1 monoclononal antibody Other Names: AB122 Drug: mFOLFOX-6 regimen mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen Drug: bevacizumab Bevacizumab is administered as part of standard chemotherapy regimen
Active Comparator: mFOLFOX-6 +/-bevacizumab Participants will receive mFOLFOX-6 +/- bevacizumab by IV infusion.	Drug: mFOLFOX-6 regimen mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen Drug: bevacizumab Bevacizumab is administered as part of standard chemotherapy regimen
Active Comparator: regorafenib Participants will receive oral regorafenib	Drug: regorafenib Regorafenib is adminstered as part of standard chemotherapy regimen
Experimental: etrumadent+ zimberelimab + AB680 Participants will receive oral etrmadenant in combination with zimberelimab +AB680 by IV infusion.	Drug: etrumadenant Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist Other Names: AB928 Drug: zimberelimab Zimberelimab is a fully human anti-PD-1 monoclononal antibody Other Names: AB122 Drug: AB680 AB680 is a cluster of differentiated CD73 Inhibitor

Outcome Measures

Primary Outcome Measures

Cohort A and B - Progression-free Survival (PFS) [From randomization until death from any cause (up to approximately 3-7 years)]
PFS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator
Cohort C - Objective Response Rate (ORR) [From randomization until death from any cause (up to approximately 3-7 years)]
ORR according to RECIST v1.1, as assessed by the Investigator
Number of Participants With Treatment-emergent Adverse Events [Up to approximately 10 Months]

Secondary Outcome Measures

Cohorts A and B - Objective Response Rate (ORR) [From randomization until death from any cause (up to approximately 3-7 years)]
ORR according to RECIST v1.1 as assessed by the Investigator
Cohorts A, B, and C- Duration of Disease Response (DoR) [From randomization until death from any cause (up to approximately 3-7 years)]
DoR according to RECIST v1.1, as assessed by the Investigator
Cohorts A, B, and C- Disease Control Rate (DCR) [From randomization until death from any cause (up to approximately 3-7 years)]
DCR according to RECIST v1.1, as assessed by the Investigator
Cohorts A and B - Overall Survival (OS) [From randomization until death from any cause (up to approximately 3-7 years)]
OS according to RECIST v1.1, as assessed by the Investigator
Observed Maximum Concentration (Cmax) of Etrumadenant and its Metabolites [From randomization until death from any cause (up to approximately 10 months)]
Cycle 1 Day 1 and Cycle 2 Day 1
Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours [AUC(0-24)] of Etrumadenant and its Metabolites [Up to 24 hours following Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days)]
Trough Concentrations of Etrumadenant and its Metabolites [Multiple timepoints up to approximately 16 months]
Cmax End of Infusion (EOI) of AB680 [At the end of infusion on Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days)]
Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours [AUC(0-336)] of AB680 [Up to 336 hours following Day 1 Cycle and Cycle 2 (each cycle is 28 days)]]
Trough Concentrations of AB680 [Multiple timepoints up to approximately 16 months]
Cmax EOI of Zimberelimab [Multiple timepoints up to approximately 16 months]
AUV(0-336) of Zimberelimab [Cycle 1 Day 1 up to 336 hours]
Trough Concentrations of Zimberelimab [Multiple timepoints up to approximately 16 months]
Number of Participants With Anti-Drug Antibodies to the Biologic Component(s) of Combination Therapy [Up to approximately 10 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female participants ≥ 18 years of age
Histologically confirmed metastatic colorectal adenocarcinoma
Must have at least 1 measurable lesion per RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy at least 3 months
Adequate hematologic and end-organ function
Negative HIV, Hep B and Hep C antibody testing
Agreement to remain abstinent or use contraceptive measures with female partners of reproductive potential, and agreement to refrain from donating sperm, for 30 days after the last dose of etrumadenant, 90 days after the last dose of zim, 180 days after mFOLFOX-6 and 180 days after bev, whichever is longer.
Inclusion Criteria for Cohort A:
Disease progression following not more than one prior line of treatment for mCRC that consisted of oxaliplatin or irinotecan containing chemotherapy in combination with a biologic agent
Inclusion Criteria for Cohort B:
Disease progression during or following not more that two separate lines of treatment for mCRC that consisted of oxaliplatin, and irinotecan containing chemotherapy in combination with a biologic agent

Exclusion Criteria:

Previous anticancer treatment within 4 weeks prior to initiation of study treatment
Prior allogeneic stem cell or solid organ transplant
Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of study treatment
Use of any live vaccines against infectious diseases within 28 days of first dose.
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
Current treatment with anti-viral therapy for HBV
Structurally unstable bone lesions suggesting impending fracture
History or leptomeningeal disease
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
History of malignancy other than colorectal cancer within 2 years prior to screening, except for malignancies such as non-melanoma skin carcinoma or ductal carcinoma in situ
Active tuberculosis
Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiating study treatment
Severe infection within 4 weeks (28 days) prior to initiation of study treatment
Significant cardiovascular disease, unstable or new onset of angina within 3 months prior to initiation of treatment, or myocardial infarction within 6 months prior to study treatment or unstable arrhythmia
Major surgical procedures, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for major surgical procedure during the study
Known allergy or hypersensitivity to any of the study drugs or their excipients
Inability to swallow medications
Malabsorption condition that would alter the absorption of orally administered medications
Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
Prior treatment with an agent targeting the adenosine pathway
Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain Barré syndrome, or multiple sclerosis
Exclusion Criteria for Cohorts A and B:
Prior treatment with immune checkpoint blockade therapies including anit-cytotoxic T lymphocyte-associated protein-4, anti PD-1, and anti-PD-L1 therapeutic antibodies
Mutation in the BRAF oncogene. Patients with unknown BRAF status will be required to undergo testing at a local laboratory and provide results at screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35233
3	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
4	Arizona Clinical Research Center, Inc	Tucson	Arizona	United States	85715
5	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
6	UCLA Hematology Oncology	Santa Monica	California	United States	90404
7	Yale Cancer Center	New Haven	Connecticut	United States	06510
8	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016-2633
9	Winship Cancer Institute at Emory University	Atlanta	Georgia	United States	30322
10	Ochsner Medical Center (OMC)	New Orleans	Louisiana	United States	70121
11	American Oncology Partners of Maryland,PA	Bethesda	Maryland	United States	20817
12	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
13	Comprehensive Cancer Centers Of Nevada	Las Vegas	Nevada	United States	89169
14	NYU Langone Medical Center - NYU Medical Oncology Associates	New York	New York	United States	10016
15	New York-Presbyterian Hospital-Columbia University Medical Center	New York	New York	United States	10032
16	University of Pennsylvania - Perelman Center for Advanced Medicine - Penn Radiation Oncology	Philadelphia	Pennsylvania	United States	19104
17	Prisma Health-Upstate	Greenville	South Carolina	United States	29605
18	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
19	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
20	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
21	University of Wisconsin School of Medicine	Madison	Wisconsin	United States	53792
22	Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux		France	33076
23	Centre Georges Francois Leclerc	Dijon		France	21000
24	Hopital Hotel Dieu	Nantes Cedex 1		France	44093
25	Groupe Hospitalier Pitie-Salpetriere-Centre De Recherche et de Medecine de l'Obesite	Paris Cedex 13		France	75651
26	Hopital Saint Antoine	Paris		France	75012
27	CHU la Miletrie	Poitiers		France	86000
28	Clinique Sainte Anne	Strasbourg		France	67085
29	Uniklinik RWTH Aachen Medizinische Klinik III	Aachen		Germany	52074
30	Charite - Universitatsmedizin Berlin - Campus Benjamin Franklin	Berlin		Germany	12203
31	Universitatsklinikum Carl Gustav Carus	Dresden		Germany	01307
32	Universitatsklinikum Essen	Essen		Germany	45147
33	Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)	Frankfurt		Germany	60488
34	Asklepios Klinik Altona	Hamburg		Germany	22763
35	Universitaeres Krebszentrum Leipzig (UCCL)-Universitatsklinikum Leipzig AoR	Leipzig		Germany	4103
36	Universitatsmedizin Mannheim GmbH	Mannheim		Germany	68167
37	Klinikum Grosshadern-Klinikum Der Ludwig-Maximilian Universitaet Muenchen	Muenchen		Germany	81377
38	Staedtisches Klinikum Muenchen Bogenhausen	Muenchen		Germany	81925
39	Ircc Istituto Per La Ricerca E La Cura Del Cancro Di Candiolo Oncologia Medica	Candiolo		Italy	10060
40	IRCCS - Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis	Castellana Grotte		Italy	70013
41	Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica	Firenze		Italy	50134
42	Instituto Europeo di Oncologia	Milano		Italy	20141
43	Azienda Ospedaliera Niguarda Ca' Granda	Milano		Italy	20162
44	Istituto Clinico Humanitas IRCCS	Rozzano		Italy	20089
45	Universita di Siena - Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte	Siena		Italy	53100
46	Chonnam National University Hwasun Hospital	Hwasun		Korea, Republic of	58128
47	Seoul National University Bundang Hospital	Seoul		Korea, Republic of	13620
48	Seoul National University Hospital (SNUH)	Seoul		Korea, Republic of	3080
49	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	3722
50	Asan Medical Center, University of Ulsan College of Medicine	Seoul		Korea, Republic of	5538
51	Samsung Medical Center	Seoul		Korea, Republic of	6351
52	Korea University Anam Hospital	Seoul		Korea, Republic of	8241
53	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
54	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
55	Hospital Universitario La Paz	Madrid		Spain	28046
56	Complejo Hospitalario de Orense	Orense		Spain	32005
57	Clinica Universidad Navarra-Sede Madrid	Pamplona		Spain	31008
58	Corporacio Sanitaria Parc Tauli	Sabadell		Spain	08208
59	Hospital Universitario Marques De Valdecilla	Santander		Spain	39008
60	Royal Marsden Hospital (RMH) - Royal Marsden NHS Foundation Trust	London	England	United Kingdom	SW3 6JJ
61	The Christie NHS Foundation Trust	Manchester	England	United Kingdom	M20 4BX
62	Belfast City Hospital	Belfast	Northern Ireland	United Kingdom	BT9 7AB
63	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
64	Beatson West of Scotland Cancer Centre	Glasgow	Scotland	United Kingdom	G12 0YN

Sponsors and Collaborators

Arcus Biosciences, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Arcus Biosciences, Inc.

ClinicalTrials.gov Identifier:

NCT04660812

Other Study ID Numbers:

ARC-9

First Posted:

Dec 9, 2020

Last Update Posted:

Jun 22, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Arcus Biosciences, Inc.

mCRC

Additional relevant MeSH terms:

Colorectal Neoplasms

Bevacizumab

Study Results

No Results Posted as of Jun 22, 2022