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

Phase 2

Active, not recruiting

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Botensilimab; Drug: Standard of Care; Drug: Balstilimab

• Registration Number: NCT05608044
• Lead Sponsor: Agenus Inc.

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2022-11-01
• Study First Submitted QC: 2022-11-01
• Study First Posted: 2022-11-08
• Study Start: 2022-11-30
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-03
• Last Update Posted: 2024-06-04
• Primary Completion: 2025-02
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 234

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.

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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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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination Botensilimab Dose 2 plus Balstilimab	Botensilimab	Participants will receive botensilimab at dose 2 given IV and balstilimab given IV.
Monotherapy Botensilimab Dose 1	Botensilimab	Participants will receive botensilimab dose 1 given IV.
Monotherapy Botensilimab Dose 2	Botensilimab	Participants will receive botensilimab dose 2 given IV.
Standard of Care	Standard of Care	Participants will receive select standard of care as determined by the investigator.
Combination Botensilimab Dose 1 plus Balstilimab	Botensilimab	Participants will receive botensilimab at dose 1 given IV and balstilimab given IV.
Combination Botensilimab Dose 1 plus Balstilimab	Balstilimab	Participants will receive botensilimab at dose 1 given IV and balstilimab given IV.
Combination Botensilimab Dose 2 plus Balstilimab	Balstilimab	Participants will receive botensilimab at dose 2 given IV and balstilimab given IV.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	First dose through up to 2 years	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).

Secondary Outcome Measures

Name	Time	Method
Duration of Response	First dose through up to 2 years	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.
Progression-free Survival	First dose through up to 3 years	Progression-free survival is defined as the time from randomization until disease progression or death, whichever occurs first, as assessed using RECIST 1.1.
Overall Survival	First dose through up to 3 years	Overall survival is defined as the time from randomization until death due to any cause.
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
Serum Balstilimab Concentration	First study dose (pre-dose and 1 hour post-dose) through up to 2 years
Number of Participants Positive for Botensilimab Anti-drug Antibodies Following Treatment with Botensilimab	First study dose (pre-dose and 1 hour post-dose) through up to 2 years
Number of Participants Positive for Balstilimab Anti-drug Antibodies Following Treatment with Balstilimab	First study dose (pre-dose and 1 hour post-dose) through up to 2 years

Trial Locations

Locations (65)

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Memorial Sloan Kettering; 🇺🇸 New York, New York, United States

Branch office of " Hadassah Medical Ltd"; 🇷🇺 Moscow, Russian Federation

Antwerp University Hospital (UZA); 🇧🇪 Edegem, Belgium

"Clinical Hospital "RZD-Medicine" of Saint Petersburg"; 🇷🇺 Saint Petersburg, Russian Federation

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, Russian Federation

Universitair Ziekenhuis Leuven; 🇧🇪 Leuven, Belgium

Vall d'Hebron Institute of Oncology (VHIO); 🇪🇸 Barcelona, Spain

Siberian State Medical University; 🇷🇺 Tomsk, Russian Federation

Clínica Universidad de Navarra - Sede Pamplona; 🇪🇸 Pamplona, Spain

Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology); 🇷🇺 Saint Petersburg, Russian Federation

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Spain

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Keck School of Medicine of the University of Southern California; 🇺🇸 Los Angeles, California, United States

University of Colorado; 🇺🇸 Denver, Colorado, United States

Tennessee Oncology Nashville (Sarah Cannon); 🇺🇸 Nashville, Tennessee, United States

Earle A. Chiles Research Institute - Robert W. Franz Cancer Center - Providence Cancer Institute; 🇺🇸 Portland, Oregon, United States

Oregon Health & Science University (OHSU); 🇺🇸 Portland, Oregon, United States

Vanderbilt University School of Medicine; 🇺🇸 Nashville, Tennessee, United States

Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University); 🇫🇷 Paris, France

Clínica Universidad de Navarra - Sede Madrid; 🇪🇸 Madrid, Spain

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, Russian Federation

Closed Joint Stock Company Medical Center "AVICENNA"; 🇷🇺 Novosibirsk, Russian Federation

BHI of the Omsk region "Clinical oncological dispensary"; 🇷🇺 Omsk, Russian Federation

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, Russian Federation

Napalkov SBHI "Saint-Petersburg clinical scientific and practical center for specialised types of medical care (oncological); 🇷🇺 Saint Petersburg, Russian Federation

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Florida Cancer Specialists and Research Institute - Lake Mary; 🇺🇸 Lake Mary, Florida, United States

Medical Oncology Hematology Consultants; 🇺🇸 Newark, Delaware, United States

Atlantic Health System - Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

Mount Sinai Hospital - New York; 🇺🇸 New York, New York, United States

Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island); 🇺🇸 East Providence, Rhode Island, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

Virginia Cancer Specialists/NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States

MDACC; 🇺🇸 Houston, Texas, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

Hospital Sirio Libanes Brasilia; 🇧🇷 Brasília, Brazil

Oncosite - Centro de Pesquisa Clinica Em Oncologia; 🇧🇷 Ijuí, Brazil

Tbilisi Central Hospital Ltd; 🇬🇪 Tbilisi, Georgia

Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa; 🇧🇷 Porto Alegre, Brazil

Instituto Sul Mineiro de Oncologia - ONCOMINAS; 🇧🇷 Pouso Alegre, Brazil

Instituto Americas; 🇧🇷 Rio de Janeiro, Brazil

Centro Paulista de Oncologia; 🇧🇷 São Paulo, Brazil

Hospital A.C. Camargo Cancer Center; 🇧🇷 São Paulo, Brazil

Service d'Oncologie Medicale - CHRU Besancon; 🇫🇷 Besançon, France

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

High Technology Hospital Medcenter Ltd; 🇬🇪 Batumi, Georgia

Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris; 🇫🇷 Villejuif, France

Innova LLC; 🇬🇪 Tbilisi, Georgia

CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC); 🇫🇷 Poitiers, France

Fondazione IRCCS Instituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Italy

Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera; 🇮🇹 Padova, Italy

Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G. E. Ostroverkhov"; 🇷🇺 Kursk, Russian Federation

Regional State Budgetary Institution of Healthcare"Altai Regional Oncology Dispensary"; 🇷🇺 Barnaul, Russian Federation

Limited Liability Company "EVIMED"; 🇷🇺 Chelyabinsk, Russian Federation

State Budgetary Institution of Health Care "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar region; 🇷🇺 Krasnodar, Russian Federation

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Texas Oncology - Austin Midtown; 🇺🇸 Austin, Texas, United States

Northwest Cancer Center Specialists - Vancouver Cancer Center - Compass Oncology Vancouver; 🇺🇸 Vancouver, Washington, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

Rocky Mountain Cancer Center - Aurora; 🇺🇸 Aurora, Colorado, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho; 🇧🇷 Jaú, São Paulo, Brazil