AzTrials
AzTrials

Metastatic Colorectal CancerPhase 2NCT05608044

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

A Phase 2 study testing Botensilimab and Balstilimab in people with Metastatic Colorectal Cancer, run by Agenus Inc. at 65 sites in 8 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Botensilimab and Balstilimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
234 participants
Where
65 sitesin 8 countries
Study dates
30 Nov 2022to Sep 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed diagnosis of unresectable and metastatic CRC adenocarcinoma.
  • The tumor must have been assessed for microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR) status per a standard local testing method.
  • Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
  • 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:
  • 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.
  • 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.
Show all 14Show fewer
  • 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.
  • Measurable disease on baseline imaging per RECIST 1.1.
  • Life expectancy ≥ 12 weeks.
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Adequate organ function.
  • Women of childbearing potential must have a negative serum pregnancy test at screening and prior to study drug administration.
  • 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.
  • No growth factor support, transfusions, or albumin administration within 14 days of randomization of study treatment.

Who cannot join

  • Tumor is MSI-H/dMMR per a standard local testing method.
  • Received programmed cell death protein 1, PD-(L)1, or CTLA-4 therapies including any immune checkpoint inhibitor or experimental immunologic agents.
  • Received regorafenib or trifluridine/tipiracil as prior therapy(ies).
  • Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction.
  • Refractory ascites.
  • 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.
Show all 30Show fewer
  • Clinically significant (that is, active) cardiovascular disease.
  • Active brain metastases or leptomeningeal metastases with certain exceptions.
  • 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.
  • Treatment with one of the following classes of drugs within the delineated time window prior to Cycle 1 Day 1 (C1D1):
  • Cytotoxic, targeted therapy or other investigational therapy within 3 weeks.
  • Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter.
  • Small molecule/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half-lives of investigational drug.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Any evidence of current interstitial lung disease (ILD) or pneumonitis, or prior history of ILD or non-infectious pneumonitis requiring glucocorticoids.
  • History of allogeneic organ transplant, stem cell transplant, or bone marrow transplant.
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • 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.
  • 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).
  • 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.
  • Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.
  • Uncontrolled infection with human immunodeficiency virus.
  • Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection.
  • Known active hepatitis C virus as determined by positive serology and confirmed by polymerase chain reaction.
  • Has urine protein ≥ 1 gram/24 hour.
  • 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).
  • Participants who require treatment with strong cytochrome P450 3A4 inducers or inhibitors.
  • Has presence of gastrointestinal condition, for example, malabsorption, that might affect the absorption of study drug(s).
  • Non-healing wound(s).
  • Symptomatic active bleeding.

Trial locations and contacts

65 sites in 8 countries.

65 sites in 8 countries

United States26 sites

  • University of Michigan

    Ann Arbor, Michigan, 48084

  • Rocky Mountain Cancer Center - Aurora

    Aurora, Colorado, 80012

  • Texas Oncology - Austin Midtown

    Austin, Texas, 78705

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Texas Oncology - Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • University of Colorado

    Denver, Colorado, 80220

  • City of Hope National Medical Center

    Duarte, California, 91010

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

    East Providence, Rhode Island, 02915

  • Virginia Cancer Specialists/NEXT Virginia

    Fairfax, Virginia, 22031

  • MDACC

    Houston, Texas, 77030

  • Florida Cancer Specialists and Research Institute - Lake Mary

    Lake Mary, Florida, 32746

  • Keck School of Medicine of the University of Southern California

    Los Angeles, California, 90033

  • Atlantic Health System - Morristown Medical Center

    Morristown, New Jersey, 07960

  • Tennessee Oncology Nashville (Sarah Cannon)

    Nashville, Tennessee, 37203

  • Vanderbilt University School of Medicine

    Nashville, Tennessee, 37215

  • Weill Cornell Medicine

    New York, New York, 10021

  • Mount Sinai Hospital - New York

    New York, New York, 10029

  • Memorial Sloan Kettering

    New York, New York, 10065

  • Medical Oncology Hematology Consultants

    Newark, Delaware, 19713

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

    Portland, Oregon, 97213

  • Oregon Health & Science University (OHSU)

    Portland, Oregon, 97239

  • HonorHealth Research Institute

    Scottsdale, Arizona, 85258

  • Swedish Cancer Institute

    Seattle, Washington, 98104

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

    Vancouver, Washington, 98684

Other trials in United States

Russia14 sites

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

    Barnaul, 656045

  • Limited Liability Company "EVIMED"

    Chelyabinsk, 454048

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

    Krasnodar, 350040

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

    Kursk, 305524

  • 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, 111123

  • 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, 119991

  • Branch office of " Hadassah Medical Ltd"

    Moscow, 121205

  • Closed Joint Stock Company Medical Center "AVICENNA"

    Novosibirsk, 630099

  • BHI of the Omsk region "Clinical oncological dispensary"

    Omsk, 644013

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

    Saint Petersburg, 195271

  • 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, 197758

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

    Saint Petersburg, 197758

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

    Saint Petersburg

  • Siberian State Medical University

    Tomsk, 634028

Other trials in Russia

Brazil8 sites

  • Hospital Sirio Libanes Brasilia

    Brasília, 70200-730

  • Oncosite - Centro de Pesquisa Clinica Em Oncologia

    Ijuí, 98700-000

  • Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

    Jaú, São Paulo, 17210-080

  • Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

    Porto Alegre, 90110-270

  • Instituto Sul Mineiro de Oncologia - ONCOMINAS

    Pouso Alegre, 37554-216

  • Instituto Americas

    Rio de Janeiro, 22775-001

  • Hospital A.C. Camargo Cancer Center

    São Paulo, 01509-010

  • Centro Paulista de Oncologia

    São Paulo, 04538-132

Other trials in Brazil

France5 sites

  • Service d'Oncologie Medicale - CHRU Besancon

    Besançon, 25000

  • Institut Paoli-Calmettes

    Marseille, 13009

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

    Paris, 75012

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

    Poitiers, 86000

  • Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris

    Villejuif, 94805

Other trials in France

Spain4 sites

  • Vall d'Hebron Institute of Oncology (VHIO)

    Barcelona, 8035

  • Clínica Universidad de Navarra - Sede Madrid

    Madrid, 28027

  • Clínica Universidad de Navarra - Sede Pamplona

    Pamplona, 31008

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

Other trials in Spain

Georgia3 sites

  • High Technology Hospital Medcenter Ltd

    Batumi, 0144

  • Innova LLC

    Tbilisi, 0159

  • Tbilisi Central Hospital Ltd

    Tbilisi, 0159

Other trials in Georgia

Italy3 sites

  • Fondazione IRCCS Instituto Nazionale dei Tumori

    Milan, 20133

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, 20162

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

    Padova, 35128

Other trials in Italy

Belgium2 sites

  • Antwerp University Hospital (UZA)

    Edegem, 2650

  • Universitair Ziekenhuis Leuven

    Leuven, 3000

Other trials in Belgium

About this study

Official title: A Randomized, Open-Label, Phase 2 Study of Botensilimab (AGEN1181) as Monotherapy and in Combination With Balstilimab (AGEN2034) or Investigator's Choice Standard of Care (Regorafenib or Trifluridine and Tipiracil) for the Treatment of Refractory Metastatic Colorectal Cancer

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.

Read the detailed description

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.

Being tested
Botensilimab, Balstilimab, Standard of Care
Keywords
Open Label, Botensilimab, AGEN1181, Balstilimab, AGEN2034, Colorectal Cancer, Regorafenib, Trifluridine, Tipiracil, Lonsurf, Immunotherapy, Pd-1, CTLA-4, Fc-enhanced, Agenus, MSS, Microsatellite stable
Medical subject headings
Colorectal Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BotensilimabDrug

    Also called AGEN1181

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

  • BalstilimabDrug

    Also called AGEN2034

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

  • Standard of CareDrug

    Regorafenib or trifluridine and tipiracil.

Study groups in NCT05608044
Study groupRoleWhat they receive
Combination Botensilimab Dose 1 plus BalstilimabExperimentalParticipants will receive botensilimab at dose 1 given IV and balstilimab given IV.
Receives: Drug: Botensilimab; Drug: Balstilimab
Combination Botensilimab Dose 2 plus BalstilimabExperimentalParticipants will receive botensilimab at dose 2 given IV and balstilimab given IV.
Receives: Drug: Botensilimab; Drug: Balstilimab
Monotherapy Botensilimab Dose 1ExperimentalParticipants will receive botensilimab dose 1 given IV.
Receives: Drug: Botensilimab
Monotherapy Botensilimab Dose 2ExperimentalParticipants will receive botensilimab dose 2 given IV.
Receives: Drug: Botensilimab
Standard of CareActive comparatorParticipants will receive select standard of care as determined by the investigator.
Receives: Drug: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    Objective response rate is defined as the proportion of participants with complete response or partial response, as assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

    Measured: First dose through up to 2 years

Secondary outcomes (8)

  1. Duration of Response

    Duration of response is defined as the time from initial objective radiographic response until disease progression or death, whichever occurs first, as assessed using RECIST 1.1.

    Measured: First dose through up to 2 years

  2. Progression-free Survival

    Progression-free survival is defined as the time from randomization until disease progression or death, whichever occurs first, as assessed using RECIST 1.1.

    Measured: First dose through up to 3 years

  3. Overall Survival

    Overall survival is defined as the time from randomization until death due to any cause.

    Measured: First dose through up to 3 years

  4. Number of Participants Experiencing Treatment-emergent Adverse Events

    Measured: First dose through up to 2 years

  5. Serum Botensilimab Concentration

    Measured: First study dose (pre-dose and 1 hour post-dose) through up to 2 years

  6. Serum Balstilimab Concentration

    Measured: First study dose (pre-dose and 1 hour post-dose) through up to 2 years

  7. Number of Participants Positive for Botensilimab Anti-drug Antibodies Following Treatment with Botensilimab

    Measured: First study dose (pre-dose and 1 hour post-dose) through up to 2 years

  8. Number of Participants Positive for Balstilimab Anti-drug Antibodies Following Treatment with Balstilimab

    Measured: First study dose (pre-dose and 1 hour post-dose) through up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2022
  2. Study start30 Nov 2022
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
234 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05608044
Sponsor's protocol ID
C-800-25
Other IDs
2022-501546-29
Status last verified
Nov 2026
First submitted
1 Nov 2022
Last updated
5 Nov 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Botensilimab and Balstilimab in people with Metastatic Colorectal Cancer, run by Agenus Inc. at 65 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, Russia, Brazil, France, Spain and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (time frame: First dose through up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05608044.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in