Metastatic colorectal cancer MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Etrumadenant
Product Code: AB928
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Etrumadenant
Current Sponsor code: AB928
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Arcus Biosciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Capable of giving signed informed consent 2.Male and female participants =18 years of age inclusive, at the time of signing the informed consent 3.Ability to comply with the study protocol in the Investigator’s judgment 4.Histologically confirmed metastatic colorectal adenocarcinoma 5.Measurable (at least one target lesion) disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation. Note: Inclusion Criterion 5 is not required for participants entering into the Safety Run-in Cohort. 6.Participants with measurable disease and accessible tumor will undergo a pre-treatment biopsy (unless an archived specimen is available) and on-treatment fresh tumor biopsy. The biopsy must not put participants at undue risk and the procedure must not be more invasive than a core biopsy as documented in the medical record by the Investigator. Fresh biopsy of a tumor lesion not previously irradiated should be obtained. Tumors progressing in a prior site of radiation may be considered after Sponsor consultation. • Participants for biopsy should have at least two measurable lesions at baseline: one for tissue sampling and one for radiographic response assessment. 7.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8.Life expectancy =3 months as determined by the Investigator 9.Adequate hematologic and end-organ function defined by the following laboratory test results at screening: a. Absolute neutrophil count =1.5 x 10^9/L (1500/µL) without granulocyte colony-stimulating factor support b. White blood cell counts =2.5x 10^9/L (2500/µL) c. Lymphocyte count =0.5 x 10^9/L (500/µL) d. Platelet count =100 x 10^9/L (100,000/µL) without transfusion e. Hemoglobin =90 g/L (9.0 g/dL) Participants must not have been transfused within 2 weeks prior to screening to meet minimum platelet and hemoglobin parameters. f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x upper limit of normal (ULN), with the following exception: i. Participants with documented liver metastases: AST and ALT =5 x ULN ii. Participants with documented liver or bone metastases: alkaline phosphatase (ALP) =5 x ULN g. ALP =5 x ULN i. If ALP >5 × ULN, then gamma-glutamyl transpeptidase must be within normal limits h. Total bilirubin =1.5 x ULN, with the following exception: i. Participants with known Gilbert syndrome: serum bilirubin level =3 x ULN i. Albumin =25 g/L (2.5 g/dL) j. Serum creatinine =1.5 x ULN or creatinine clearance =30 mL/min as determined by Cockcroft-Gault equation (Cockcroft and Gault, 1976) 10.Negative human immunodeficiency virus (HIV) test at screening. Eligible participants must not have evidence of chronic HIV infection at screening 11.Negative hepatitis B surface antigen (HBsAg) and core antibody (HBcAb) tests, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV test will be performed only for participants who have a positive total HBcAb test. Eligible participants must not have evidence of chronic viral hepatitis infection at screening 12.Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening. The HCV RNA test will be performed only for participants who have a positive HCV antibody test. El
Exclusion criteria
Exclusion criteria: 1.Prior anticancer treatment for the disease under study, including approved agents, systemic radiotherapy, or investigational therapy, within 4 weeks (or 5 half-lives) whichever is shorter prior to initiation of study treatment. Prior focal radiotherapy must be completed at least 2 weeks prior to the initiation of study treatment 2.QTc =480 msec using Fredericia’s QT correction formula. 3.Prior allogeneic stem cell or solid organ transplantation 4.Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks (or 5 half-lives) whichever is shorter prior to initiation of study treatment 5.Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor-a agents) administered at >10 mg/day prednisone or equivalent within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment, with the following exceptions: a. Participants who received low dose (=10 mg/day prednisone or equivalent), systemic immunosuppressant medications or a one-time pulse dose of systemic immunosuppressant medication (eg, 48 hours of corticosteroids for a contrast allergy) are eligible after Medical Monitor approval. b. Participants who received mineralocorticoids (eg, fludrocortisone), inhaled or intranasal corticosteroids for chronic obstructive pulmonary disease or asthma, or low dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible after Medical Monitor approval. 6.Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the last dose of study treatment 7.Current treatment with anti-viral therapy for HBV 8.Structurally unstable bone lesions suggesting impending fracture 9.Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases a. Participants with a history of treated CNS metastases are eligible, if all of the following criteria are met: i. The participant has no history of intracranial hemorrhage or spinal cord hemorrhage. ii. Metastases are limited to the cerebellum or the supratentorial region. iii. There is no evidence of interim progression between completion of CNS directed therapy and the screening brain scan. iv. The participant has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole brain radiotherapy within 14 days prior to initiation of study treatment. v. The participant has no ongoing requirement for corticosteroids as therapy for CNS disease. Anti-convulsant therapy at a stable dose is permitted. b. Asymptomatic participants with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan 10.History of leptomeningeal disease 11.History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted b. Participants with ground-glass opacities of unknown significance may be eligible following a discussion with th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Cohorts A (2L), B (3L), and C (>3L) - Efficacy: To evaluate the antitumor activity of etruma-based treatment combinations • All Cohorts (including Safety Run-in Cohort) - Safety: To evaluate the safety and tolerability of etruma-based treatment combinations;Secondary Objective: • Cohorts A (2L), B (3L), and C (>3L) - To evaluate clinical activity of etruma-based treatment combinations • All Cohorts (including Safety Run-in Cohort) - To determine the pharmacokinetic (PK) profile for components of etruma-based treatment combinations • All Cohorts (including Safety Run-in Cohort) - To assess immunogenicity of the biologic component(s) of combination therapy where appropriate;Primary end point(s): Efficacy: Cohort A (2nd line [2L]) • Progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator Cohort B (3rd line [3L]) (Co-primary) • PFS according to RECIST v1.1 as assessed by the Investigator • Overall survival (OS) Cohort C (>3 lines [>3L]) • Objective response rate (ORR) according to RECIST v1.1, as assessed by the Investigator Safety: All Cohorts (including Safety Run-in Cohort) • Incidence and severity of adverse events (AEs) and serious adverse events (SAEs);Timepoint(s) of evaluation of this end point: Efficacy: Cohort A (2nd line [2L]): PFS Defined as the time from treatment assignment until first documentation of progressive disease or death, whichever occurs first. Cohort B (3rd line [3L]) (Co-primary): PFS and OS PFS (defined above) and OS, defined as the time from treatment assignment until death due to any cause. Cohort C (>3 lines [>3L]): ORR Defined as the proportion of participants with a best overall response of CR or PR according to RECIST v1.1 Safety: Throughout the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Cohort A (2L) • ORR according to RECIST v1.1, as assessed by the Investigator, duration of response (DoR; defined as the time from first documentation of disease response [complete response (CR) or partial response (PR)] until first documentation of confirmed progressive disease), disease control rate (DCR; defined as CR, PR, or stable disease [SD] for >12 weeks), and OS Cohort B (3L) • ORR, DoR, and DCR (CR, PR, or SD for >12 weeks) according to RECIST v1.1, as assessed by the Investigator. Cohort C (>3L) • DoR and DCR (CR, PR, or SD for >12 weeks) according to RECIST v1.1, as assessed by the Investigator All Cohorts (including Safety Run-in Cohort) • Serum/plasma concentration and PK parameters for components of etruma-based combination therapy All Cohorts (including Safety Run-in Cohort) • Number and percentage of participants who develop antidrug antibodies (ADAs) to the biologic component(s) of combination therapy;Timepoint(s) of evaluation of this end point: Cohort A (2L): ORR Defined as the proportion of participants with a best overall response of CR or PR according to RECIST v1.1. DoR defined as the time from first documentation of disease response (CR or PR) until first documentation of confirmed progressive disease. DCR defined as the proportion of participants with a best overall response of CR, PR, or SD. The duration of time required for a participant with SD to be considered in disease control is >12 weeks. OS Defined as the time from treatment assignment until death due to any cause. • Cohort B (3L): ORR, DoR, and DCR (as defined above) • Cohort C (>3L): DoR and DCR (as defined above) All cohorts Throughout the trial | — |
Countries
France, Germany, Italy, Korea, Republic of, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Inquiry
Arcus Biosciences, Inc.
Outcome results
None listed