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

NCT05608044 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: C-800-252022-501546-29
• Study Type: interventional
• Target: 234
• Locations: 8 countries
• Sites: 65

Brief 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.

Conditions

Metastatic Colorectal Cancer

Keywords

Open Label; Botensilimab; AGEN1181; Balstilimab; AGEN2034; Colorectal Cancer; Regorafenib; Trifluridine; Tipiracil; Lonsurf; Immunotherapy; Pd-1; CTLA-4; Fc-enhanced; Agenus; MSS; Microsatellite stable

Outcome Measures

Primary Outcomes (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).

  First dose through up to 2 years

Secondary Outcomes (8)

• Duration of Response

  First dose through up to 2 years

• Progression-free Survival

  First dose through up to 3 years

• Overall Survival

  First dose through up to 3 years

• Number of Participants Experiencing Treatment-emergent Adverse Events

  First dose through up to 2 years

• Serum Botensilimab Concentration

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

Study Arms (5)

Combination Botensilimab Dose 1 plus Balstilimab

EXPERIMENTAL

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

Drug: Botensilimab; Drug: Balstilimab

Combination Botensilimab Dose 2 plus Balstilimab

EXPERIMENTAL

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

Drug: Botensilimab; Drug: Balstilimab

Monotherapy Botensilimab Dose 1

EXPERIMENTAL

Participants will receive botensilimab dose 1 given IV.

Drug: Botensilimab

Monotherapy Botensilimab Dose 2

EXPERIMENTAL

Participants will receive botensilimab dose 2 given IV.

Drug: Botensilimab

Standard of Care

ACTIVE COMPARATOR

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

Drug: Standard of Care

Interventions

Botensilimab DRUG

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

Also known as: AGEN1181

Combination Botensilimab Dose 1 plus Balstilimab; Combination Botensilimab Dose 2 plus Balstilimab; Monotherapy Botensilimab Dose 1; Monotherapy Botensilimab Dose 2

Balstilimab DRUG

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

Also known as: AGEN2034

Combination Botensilimab Dose 1 plus Balstilimab; Combination Botensilimab Dose 2 plus Balstilimab

Standard of Care DRUG

Regorafenib or trifluridine and tipiracil.

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (65)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Keck School of Medicine of the University of Southern California

Los Angeles, California, 90033, United States

Location

Rocky Mountain Cancer Center - Aurora

Aurora, Colorado, 80012, United States

Location

University of Colorado

Denver, Colorado, 80220, United States

Location

Medical Oncology Hematology Consultants

Newark, Delaware, 19713, United States

Location

Florida Cancer Specialists and Research Institute - Lake Mary

Lake Mary, Florida, 32746, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48084, United States

Location

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Mount Sinai Hospital - New York

New York, New York, 10029, United States

Location

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

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

Portland, Oregon, 97213, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

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

East Providence, Rhode Island, 02915, United States

Location

Tennessee Oncology Nashville (Sarah Cannon)

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37215, United States

Location

Texas Oncology - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MDACC

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists/NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

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

Vancouver, Washington, 98684, United States

Location

Antwerp University Hospital (UZA)

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho

Jaú, São Paulo, 17210-080, Brazil

Location

Hospital Sirio Libanes Brasilia

Brasília, 70200-730, Brazil

Location

Oncosite - Centro de Pesquisa Clinica Em Oncologia

Ijuí, 98700-000, Brazil

Location

Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa

Porto Alegre, 90110-270, Brazil

Location

Instituto Sul Mineiro de Oncologia - ONCOMINAS

Pouso Alegre, 37554-216, Brazil

Location

Instituto Americas

Rio de Janeiro, 22775-001, Brazil

Location

Hospital A.C. Camargo Cancer Center

São Paulo, 01509-010, Brazil

Location

Centro Paulista de Oncologia

São Paulo, 04538-132, Brazil

Location

Service d'Oncologie Medicale - CHRU Besancon

Besançon, 25000, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

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

Paris, 75012, France

Location

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

Poitiers, 86000, France

Location

Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris

Villejuif, 94805, France

Location

High Technology Hospital Medcenter Ltd

Batumi, 0144, Georgia

Location

Innova LLC

Tbilisi, 0159, Georgia

Location

Tbilisi Central Hospital Ltd

Tbilisi, 0159, Georgia

Location

Fondazione IRCCS Instituto Nazionale dei Tumori

Milan, 20133, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

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

Padua, 35128, Italy

Location

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

Barnaul, 656045, Russia

Location

Limited Liability Company "EVIMED"

Chelyabinsk, 454048, Russia

Location

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

Krasnodar, 350040, Russia

Location

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

Kursk, 305524, Russia

Location

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

Location

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

Location

Branch office of " Hadassah Medical Ltd"

Moscow, 121205, Russia

Location

Closed Joint Stock Company Medical Center "AVICENNA"

Novosibirsk, 630099, Russia

Location

BHI of the Omsk region "Clinical oncological dispensary"

Omsk, 644013, Russia

Location

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

Saint Petersburg, 195271, Russia

Location

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

Location

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

Saint Petersburg, 197758, Russia

Location

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

Saint Petersburg, Russia

Location

Siberian State Medical University

Tomsk, 634028, Russia

Location

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 8035, Spain

Location

Clínica Universidad de Navarra - Sede Madrid

Madrid, 28027, Spain

Location

Clínica Universidad de Navarra - Sede Pamplona

Pamplona, 31008, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

balstilimab; Standard of Care

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 8, 2022
• Study Start: November 30, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 4, 2025

Record last verified: 2025-09

Locations

BR (8); RU (14); FR (5); ES (4); BE (2); GE (3); US (26); IT (3)