Clinical trial NCT04660812: An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer.
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: mCRC
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2020-12-09
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 than 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 anti-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

Primary outcomes:
measure: Cohort A and B - Progression-free Survival (PFS)
timeFrame: From randomization until death from any cause (up to approximately 3-7 years)
measure: Cohort C - Objective Response Rate (ORR)
timeFrame: From randomization until death from any cause (up to approximately 3-7 years)
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Up to approximately 10 Months
Secondary outcomes:
measure: Cohorts A and B - Objective Response Rate (ORR)
timeFrame: From randomization until death from any cause (up to approximately 3-7 years)
measure: Cohorts A, B, and C- Duration of Disease Response (DoR)
timeFrame: From randomization until death from any cause (up to approximately 3-7 years)
measure: Cohorts A, B, and C- Disease Control Rate (DCR)
timeFrame: From randomization until death from any cause (up to approximately 3-7 years)
measure: Cohorts A and B - Overall Survival (OS)
timeFrame: From randomization until death from any cause (up to approximately 3-7 years)
measure: Observed Maximum Concentration (Cmax) of Etrumadenant and its Metabolites
timeFrame: From randomization until death from any cause (up to approximately 10 months)
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours [AUC(0-24)] of Etrumadenant and its Metabolites
timeFrame: Up to 24 hours following Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days)
measure: Trough Concentrations of Etrumadenant and its Metabolites
timeFrame: Multiple timepoints up to approximately 16 months
measure: Cmax End of Infusion (EOI) of AB680
timeFrame: At the end of infusion on Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days)
measure: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours [AUC(0-336)] of AB680
timeFrame: Up to 336 hours following Day 1 Cycle and Cycle 2 (each cycle is 28 days)]
measure: Trough Concentrations of AB680
timeFrame: Multiple timepoints up to approximately 16 months
measure: Cmax EOI of Zimberelimab
timeFrame: Multiple timepoints up to approximately 16 months
measure: AUV(0-336) of Zimberelimab
timeFrame: Cycle 1 Day 1 up to 336 hours
measure: Trough Concentrations of Zimberelimab
timeFrame: Multiple timepoints up to approximately 16 months
measure: Number of Participants With Anti-Drug Antibodies to the Biologic Component(s) of Combination Therapy
timeFrame: Up to approximately 10 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Center Inc
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Winship Cancer Institute at Emory University
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Medical Center (OMC)
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland PA
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers Of Nevada
state: Nevada
city: New York
country: United States
facility: NYU Langone Medical Center - NYU Medical Oncology Associates
state: New York
city: New York
country: United States
facility: New York-Presbyterian Hospital-Columbia University Medical Center
state: New York
city: Greenville
country: United States
facility: Prisma Health-Upstate
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin School of Medicine
state: Wisconsin
city: Bordeaux
country: France
facility: Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Nantes Cedex 1
country: France
facility: Hopital Hotel Dieu
city: Paris Cedex 13
country: France
facility: Groupe Hospitalier Pitie-Salpetriere-Centre De Recherche et de Medecine de l'Obesite
city: Paris
country: France
facility: Hopital Saint Antoine
city: Poitiers
country: France
facility: CHU la Miletrie
city: Strasbourg
country: France
facility: Clinique Sainte Anne
city: Castellana Grotte
country: Italy
facility: IRCCS - Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
city: Milano
country: Italy
facility: Azienda Ospedaliera Niguarda Ca' Granda
city: Milano
country: Italy
facility: Instituto Europeo di Oncologia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas IRCCS
city: Siena
country: Italy
facility: Universita di Siena - Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital (SNUH)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital | Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center | University of Ulsan College of Medicine
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Orense
country: Spain
facility: Complejo Hospitalario de Orense
city: Pamplona
country: Spain
facility: Clinica Universidad Navarra-Sede Madrid
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
Study officials:
affiliation: Arcus Biosciences
name: Medical Director
role: STUDY_DIRECTOR
References: