A Study Evaluating the Efficacy and Safety of AB928-Based Treatment Combinations in Patients with Metastatic Colorectal Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arcus Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Aug 2021 → 10 Jun 2025

Decision date (initial)

2024-09-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Arcus Biosciences, Inc. · Gilead Sciences, Inc.

External identifiers

EU CT number

2024-511158-36-00

EudraCT number

2020-005386-13

ClinicalTrials.gov

NCT04660812

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Others, Efficacy

1. Cohorts A (2L), B (3L), and C (>3L): Efficacy: To evaluate the antitumor activity of etruma-based treatment combinations
2. All Cohorts (including Safety Run-in Cohort): Safety: To evaluate the safety and tolerability of etruma-based treatment combinations

Secondary objectives 3

1. Cohorts A (2L), B (3L), and C (>3L): To evaluate clinical activity of etruma-based treatment combinations
2. All Cohorts (including Safety Run-in Cohort): To determine the pharmacokinetic (PK) profile for components of etruma-based treatment combinations
3. All Cohorts (including Safety Run-in Cohort): To assess immunogenicity of the biologic component(s) of combination therapy where appropriate

Conditions and MedDRA coding

Metastatic colorectal cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male and female participants ≥18 years of age inclusive, at the time of signing the informed consent
2. Histologically confirmed metastatic colorectal adenocarcinoma
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Life expectancy ≥3 months as determined by the Investigator
6. Adequate hematologic and end-organ function
7. Negative HIV, Hep B and Hep C antibody testing
8. 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.
9. 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
10. 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 23

1. Previous anticancer treatment within 4 weeks prior to initiation of study treatment
2. Prior allogeneic stem cell or solid organ transplantation
3. Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of study treatment
4. Use of any live vaccines against infectious diseases within 28 days of first dose
5. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
6. Current treatment with anti-viral therapy for HBV
7. Structurally unstable bone lesions suggesting impending fracture
8. History or leptomeningeal disease
9. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
10. History of malignancy other than colorectal cancer within 2 years prior to screening, except for malignancies with a negligible risk of metastasis or death, such as non-melanoma skin carcinoma or ductal carcinoma in situ
11. Active tuberculosis
12. Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiating study treatment
13. Severe infection within 4 weeks (28 days) prior to initiation of study treatment
14. 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
15. 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
16. Known allergy or hypersensitivity to any of the study drugs or their excipients
17. Inability to swallow medications
18. Malabsorption condition that would alter the absorption of orally administered medications
19. Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
20. Prior treatment with an agent targeting the adenosine pathway
21. 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
22. 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
23. Exclusion Criteria for Cohorts A and B: 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

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

Secondary endpoints 14

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arcus Biosciences Inc.

Sponsor organisation

Arcus Biosciences Inc.

Address

3928 Point Eden Way

City

Hayward

Postcode

94545-3719

Country

United States

Scientific contact point

Organisation

Arcus Biosciences Inc.

Contact name

Medical Director

Public contact point

Organisation

Arcus Biosciences Inc.

Contact name

Medical Director

Third parties 12

Locations

3 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications