New drug combo aims to shrink Hard-to-Treat colorectal tumors

NCT ID NCT05608044

Disease control Sponsor: Agenus Inc. Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jun 26, 2026 · Updated 1 time

Summary

This phase 2 trial tests two experimental immunotherapy drugs, botensilimab and balstilimab, alone or together, against standard chemotherapy in 234 people with metastatic colorectal cancer that has not responded to prior treatments. The goal is to see if these drugs can shrink tumors or slow disease progression. Participants are randomly assigned to receive the new drugs or standard care.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Botensilimab and balstilimab (immunotherapy drugs)
What this could lead to: If successful, this could offer a new treatment option for people with advanced colorectal cancer that has stopped responding to standard therapies.
What could go wrong: This is an early-phase trial with a small number of participants, so results may not apply to everyone. Immunotherapies can cause serious side effects like inflammation in healthy organs.

Why investors are watching

Agenus is a very small company, and this Phase 2 trial tests its drug botensilimab, alone or with balstilimab, against standard care in patients with advanced colorectal cancer that no longer responds to other treatments. For a micro-cap, a successful readout in a hard-to-treat cancer could be the main driver of the company's value, while a failure would leave it with few other options.

If it works: If the drugs show better disease control than standard care, Agenus could gain credibility and a path toward larger trials or a partnership. A positive result might also validate its approach in a cancer type where many patients need new options.

If it fails: Trials in refractory metastatic cancer often fail, and this one has no guarantee of success. A negative or unclear result could hurt the company's prospects, and delays in enrollment or data could also weigh on it.

AI-written from the trial record. Speculative, and not investment advice.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

234 people

The number who actually took part.

Started

Nov 2022

Expected to finish

Sep 2029

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.

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Conditions

The condition(s) this trial relates to.

autosomal dominant Parkinson disease 4 colorectal adenocarcinoma colorectal cancer colorectal neoplasm type 1 diabetes mellitus 12

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Metastatic colorectal cancer

Contacts and locations

Locations

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

Saint Petersburg, 195271, Russia
ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy
Antwerp University Hospital (UZA)

Edegem, 2650, Belgium
Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, 07960, United States
BHI of the Omsk region "Clinical oncological dispensary"

Omsk, 644013, Russia
Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States
Branch office of " Hadassah Medical Ltd"

Moscow, 121205, Russia
CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)

Poitiers, 86000, France
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

Porto Alegre, 90110-270, Brazil
Centro Paulista de Oncologia

São Paulo, 04538-132, Brazil
Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

Jaú, São Paulo, 17210-080, Brazil
City of Hope National Medical Center

Duarte, California, 91010, United States
Cleveland Clinic

Cleveland, Ohio, 44195, United States
Closed Joint Stock Company Medical Center "AVICENNA"

Novosibirsk, 630099, Russia
Clínica Universidad de Navarra - Sede Madrid

Madrid, 28027, Spain
Clínica Universidad de Navarra - Sede Pamplona

Pamplona, 31008, Spain
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Earle A. Chiles Research Institute - Robert W. Franz Cancer Center - Providence Cancer Institute

Portland, Oregon, 97213, United States
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, Russia
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, Russia
Florida Cancer Specialists and Research Institute - Lake Mary

Lake Mary, Florida, 32746, United States
Fondazione IRCCS Instituto Nazionale dei Tumori

Milan, 20133, Italy
High Technology Hospital Medcenter Ltd

Batumi, 0144, Georgia
HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States
Hospital A.C. Camargo Cancer Center

São Paulo, 01509-010, Brazil
Hospital Sirio Libanes Brasilia

Brasília, 70200-730, Brazil
Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain
Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University)

Paris, 75012, France
Innova LLC

Tbilisi, 0159, Georgia
Institut Paoli-Calmettes

Marseille, 13009, France
Instituto Americas

Rio de Janeiro, 22775-001, Brazil
Instituto Sul Mineiro de Oncologia - ONCOMINAS

Pouso Alegre, 37554-216, Brazil
Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera

Padova, 35128, Italy
Keck School of Medicine of the University of Southern California

Los Angeles, California, 90033, United States
Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island)

East Providence, Rhode Island, 02915, United States
Limited Liability Company "EVIMED"

Chelyabinsk, 454048, Russia
MDACC

Houston, Texas, 77030, United States
Medical Oncology Hematology Consultants

Newark, Delaware, 19713, United States
Memorial Sloan Kettering

New York, New York, 10065, United States
Mount Sinai Hospital - New York

New York, New York, 10029, United States
Napalkov SBHI "Saint-Petersburg clinical scientific and practical center for specialised types of medical care (oncological)

Saint Petersburg, 197758, Russia
Northwest Cancer Center Specialists - Vancouver Cancer Center - Compass Oncology Vancouver

Vancouver, Washington, 98684, United States
Oncosite - Centro de Pesquisa Clinica Em Oncologia

Ijuí, 98700-000, Brazil
Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States
Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G. E. Ostroverkhov"

Kursk, 305524, Russia
Regional State Budgetary Institution of Healthcare"Altai Regional Oncology Dispensary"

Barnaul, 656045, Russia
Rocky Mountain Cancer Center - Aurora

Aurora, Colorado, 80012, United States
Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)

Saint Petersburg, Russia
Service d'Oncologie Medicale - CHRU Besancon

Besançon, 25000, France
Siberian State Medical University

Tomsk, 634028, Russia
State Budgetary Institution of Health Care "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar region

Krasnodar, 350040, Russia
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, Russia
Swedish Cancer Institute

Seattle, Washington, 98104, United States
Tbilisi Central Hospital Ltd

Tbilisi, 0159, Georgia
Tennessee Oncology Nashville (Sarah Cannon)

Nashville, Tennessee, 37203, United States
Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States
Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium
University of Colorado

Denver, Colorado, 80220, United States
University of Michigan

Ann Arbor, Michigan, 48084, United States
Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris

Villejuif, 94805, France
Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 8035, Spain
Vanderbilt University School of Medicine

Nashville, Tennessee, 37215, United States
Virginia Cancer Specialists/NEXT Virginia

Fairfax, Virginia, 22031, United States
Weill Cornell Medicine

New York, New York, 10021, United States

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