A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer

NCT ID: NCT05608044

Last Updated: 2025-09-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

234 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-30

Study Completion Date

2029-09-30

Brief Summary

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This is an open-label, Phase 2, multicenter study to evaluate the efficacy, safety, tolerability, and pharmacokinetic profiles of botensilimab as monotherapy and in combination with balstilimab or standard-of-care treatments in participants with refractory metastatic colorectal cancer.

Detailed Description

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This study will enroll adult participants with a confirmed diagnosis of unresectable metastatic colorectal adenocarcinoma (CRC) who have had prior chemotherapy for metastatic or recurrent CRC.

This study will consist of 5 cohorts. In the first and second cohorts, participants will receive 1 of 2 different doses of botensilimab intravenously (IV) and balstilimab IV. In the third and fourth cohorts, participants will receive 1 of 2 different doses of botensilimab. In the fifth cohort, participants will receive standard of care consisting of the investigator's choice of regorafenib or trifluridine and tipiracil.

Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Combination Botensilimab Dose 1 plus Balstilimab

Participants will receive botensilimab at dose 1 given IV and balstilimab given IV.

Group Type EXPERIMENTAL

Botensilimab

Intervention Type DRUG

An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.

Balstilimab

Intervention Type DRUG

An anti-programmed death (ligand) 1 \[PD-(L)1\] monoclonal antibody.

Combination Botensilimab Dose 2 plus Balstilimab

Participants will receive botensilimab at dose 2 given IV and balstilimab given IV.

Group Type EXPERIMENTAL

Botensilimab

Intervention Type DRUG

An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.

Balstilimab

Intervention Type DRUG

An anti-programmed death (ligand) 1 \[PD-(L)1\] monoclonal antibody.

Monotherapy Botensilimab Dose 1

Participants will receive botensilimab dose 1 given IV.

Group Type EXPERIMENTAL

Botensilimab

Intervention Type DRUG

An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.

Monotherapy Botensilimab Dose 2

Participants will receive botensilimab dose 2 given IV.

Group Type EXPERIMENTAL

Botensilimab

Intervention Type DRUG

An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.

Standard of Care

Participants will receive select standard of care as determined by the investigator.

Group Type ACTIVE_COMPARATOR

Standard of Care

Intervention Type DRUG

Regorafenib or trifluridine and tipiracil.

Interventions

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Botensilimab

An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.

Intervention Type DRUG

Balstilimab

An anti-programmed death (ligand) 1 \[PD-(L)1\] monoclonal antibody.

Intervention Type DRUG

Standard of Care

Regorafenib or trifluridine and tipiracil.

Intervention Type DRUG

Other Intervention Names

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AGEN1181 AGEN2034

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed diagnosis of unresectable and metastatic CRC adenocarcinoma.
2. The tumor must have been assessed for microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR) status per a standard local testing method.
3. Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
4. Must have received at least 1 prior chemotherapy regimen for metastatic or recurrent CRC as follows where approved and locally available in the country of randomization:

1. Standard chemotherapy/therapy including all of the following agents (if eligible and no contraindication): a fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab or biosimilars, an anti-epidermal growth factor receptor antibody (cetuximab or panitumumab), and v-raf murine sarcoma viral oncogene homolog B1 inhibitor/BRAF (encorafenib), if applicable.
2. Participants must have progressed while receiving or within 3 months of the last administration of their last line of standard therapy or be unable to tolerate any of these standard treatments.
3. Participants who received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy can count this as a line of therapy.
5. Measurable disease on baseline imaging per RECIST 1.1.
6. Life expectancy ≥ 12 weeks.
7. Eastern Cooperative Oncology Group performance status of 0 or 1.
8. Adequate organ function.
9. Women of childbearing potential must have a negative serum pregnancy test at screening and prior to study drug administration.
10. Male participants with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study, starting with the Screening visit through 2-6 months, depending upon assigned study treatment. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
11. No growth factor support, transfusions, or albumin administration within 14 days of randomization of study treatment.

Exclusion Criteria

1. Tumor is MSI-H/dMMR per a standard local testing method.
2. Received programmed cell death protein 1, PD-(L)1, or CTLA-4 therapies including any immune checkpoint inhibitor or experimental immunologic agents.
3. Received regorafenib or trifluridine/tipiracil as prior therapy(ies).
4. Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction.
5. Refractory ascites.
6. Liver metastases by computed tomography or magnetic resonance imaging. Note: Participants with definitively treated liver metastases (this includes surgical resection, including microwave or radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemotherapy alone) may be eligible if they were treated at least 6 months prior to enrollment with no evidence of metastatic disease in the liver on subsequent imaging.
7. Clinically significant (that is, active) cardiovascular disease.
8. Active brain metastases or leptomeningeal metastases with certain exceptions.
9. Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment. Participants with history of prior early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for active surveillance, or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.
10. Treatment with one of the following classes of drugs within the delineated time window prior to Cycle 1 Day 1 (C1D1):

1. Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
2. Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
3. Small molecule/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half-lives of investigational drug.
11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
12. Any evidence of current interstitial lung disease (ILD) or pneumonitis, or prior history of ILD or non-infectious pneumonitis requiring glucocorticoids.
13. History of allogeneic organ transplant, stem cell transplant, or bone marrow transplant.
14. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
15. Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 milligrams \[mg\] daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses (≤ 10 mg daily prednisone equivalent) are permitted in the absence of active autoimmune disease.
16. Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years of the start of study treatment (that is, with use of disease-modifying agents or immunosuppressive drugs).
17. History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
18. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
19. Uncontrolled infection with human immunodeficiency virus.
20. Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection.
21. Known active hepatitis C virus as determined by positive serology and confirmed by polymerase chain reaction.
22. Has urine protein ≥ 1 gram/24 hour.
23. Uncontrolled hypertension: systolic pressure ≥ 150 millimeters of mercury (mmHg) or diastolic pressure ≥ 90 mmHg on repeated measurements that cannot be managed by standard antihypertension medications ≤ 28 days before the first dose of study drug(s).
24. Participants who require treatment with strong cytochrome P450 3A4 inducers or inhibitors.
25. Has presence of gastrointestinal condition, for example, malabsorption, that might affect the absorption of study drug(s).
26. Non-healing wound(s).
27. Symptomatic active bleeding.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Agenus Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Agenus Inc.

Locations

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HonorHealth Research Institute

Scottsdale, Arizona, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

Keck School of Medicine of the University of Southern California

Los Angeles, California, United States

Site Status

Rocky Mountain Cancer Center - Aurora

Aurora, Colorado, United States

Site Status

University of Colorado

Denver, Colorado, United States

Site Status

Medical Oncology Hematology Consultants

Newark, Delaware, United States

Site Status

Florida Cancer Specialists and Research Institute - Lake Mary

Lake Mary, Florida, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

Mount Sinai Hospital - New York

New York, New York, United States

Site Status

Memorial Sloan Kettering

New York, New York, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Earle A. Chiles Research Institute - Robert W. Franz Cancer Center - Providence Cancer Institute

Portland, Oregon, United States

Site Status

Oregon Health & Science University (OHSU)

Portland, Oregon, United States

Site Status

Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island)

East Providence, Rhode Island, United States

Site Status

Tennessee Oncology Nashville (Sarah Cannon)

Nashville, Tennessee, United States

Site Status

Vanderbilt University School of Medicine

Nashville, Tennessee, United States

Site Status

Texas Oncology - Austin Midtown

Austin, Texas, United States

Site Status

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

MDACC

Houston, Texas, United States

Site Status

Virginia Cancer Specialists/NEXT Virginia

Fairfax, Virginia, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Northwest Cancer Center Specialists - Vancouver Cancer Center - Compass Oncology Vancouver

Vancouver, Washington, United States

Site Status

Antwerp University Hospital (UZA)

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Site Status

Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

Jaú, São Paulo, Brazil

Site Status

Hospital Sirio Libanes Brasilia

Brasília, , Brazil

Site Status

Oncosite - Centro de Pesquisa Clinica Em Oncologia

Ijuí, , Brazil

Site Status

High Technology Hospital Medcenter Ltd

Batumi, , Georgia

Site Status

Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

Porto Alegre, , Brazil

Site Status

Instituto Sul Mineiro de Oncologia - ONCOMINAS

Pouso Alegre, , Brazil

Site Status

Instituto Americas

Rio de Janeiro, , Brazil

Site Status

Hospital A.C. Camargo Cancer Center

São Paulo, , Brazil

Site Status

Centro Paulista de Oncologia

São Paulo, , Brazil

Site Status

Service d'Oncologie Medicale - CHRU Besancon

Besançon, , France

Site Status

Institut Paoli-Calmettes

Marseille, , France

Site Status

Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University)

Paris, , France

Site Status

CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)

Poitiers, , France

Site Status

Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris

Villejuif, , France

Site Status

Innova LLC

Tbilisi, , Georgia

Site Status

Tbilisi Central Hospital Ltd

Tbilisi, , Georgia

Site Status

Fondazione IRCCS Instituto Nazionale dei Tumori

Milan, , Italy

Site Status

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera

Padua, , Italy

Site Status

Regional State Budgetary Institution of Healthcare"Altai Regional Oncology Dispensary"

Barnaul, , Russia

Site Status

Limited Liability Company "EVIMED"

Chelyabinsk, , Russia

Site Status

Napalkov SBHI "Saint-Petersburg clinical scientific and practical center for specialised types of medical care (oncological)

Saint Petersburg, , Russia

Site Status

State Budgetary Institution of Health Care "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar region

Krasnodar, , Russia

Site Status

Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G. E. Ostroverkhov"

Kursk, , Russia

Site Status

Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)

Saint Petersburg, , Russia

Site Status

Siberian State Medical University

Tomsk, , Russia

Site Status

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Site Status

State Budgetary Institution of Healthcare of the City of Moscow "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of the Department of Health of the City of Moscow"

Moscow, , Russia

Site Status

Clínica Universidad de Navarra - Sede Madrid

Madrid, , Spain

Site Status

Clínica Universidad de Navarra - Sede Pamplona

Pamplona, , Spain

Site Status

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status

Federal State Autonomous Educational Institution of Higher Education I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Moscow, , Russia

Site Status

Branch office of " Hadassah Medical Ltd"

Moscow, , Russia

Site Status

Closed Joint Stock Company Medical Center "AVICENNA"

Novosibirsk, , Russia

Site Status

BHI of the Omsk region "Clinical oncological dispensary"

Omsk, , Russia

Site Status

"Clinical Hospital "RZD-Medicine" of Saint Petersburg"

Saint Petersburg, , Russia

Site Status

Federal State Budgetary Institution "National Medical Research Center of Oncology named after N.N.Petrov" of the Ministry of Health of the Russian Federation

Saint Petersburg, , Russia

Site Status

Countries

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United States Belgium Brazil France Georgia Italy Russia Spain

Other Identifiers

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2022-501546-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C-800-25

Identifier Type: -

Identifier Source: org_study_id

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