Trial Title:
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
NCT ID:
NCT05608044
Condition:
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Open Label
Botensilimab
AGEN1181
Balstilimab
AGEN2034
Colorectal Cancer
Regorafenib
Trifluridine
Tipiracil
Lonsurf
Immunotherapy
Pd-1
CTLA-4
Fc-enhanced
Agenus
MSS
Microsatellite stable
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Botensilimab
Description:
An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.
Arm group label:
Combination Botensilimab Dose 1 plus Balstilimab
Arm group label:
Combination Botensilimab Dose 2 plus Balstilimab
Arm group label:
Monotherapy Botensilimab Dose 1
Arm group label:
Monotherapy Botensilimab Dose 2
Other name:
AGEN1181
Intervention type:
Drug
Intervention name:
Balstilimab
Description:
An anti-programmed death (ligand) 1 [PD-(L)1] monoclonal antibody.
Arm group label:
Combination Botensilimab Dose 1 plus Balstilimab
Arm group label:
Combination Botensilimab Dose 2 plus Balstilimab
Other name:
AGEN2034
Intervention type:
Drug
Intervention name:
Standard of Care
Description:
Regorafenib or trifluridine and tipiracil.
Arm group label:
Standard of Care
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
HonorHealth Research Institute
Address:
City:
Scottsdale
Zip:
85258
Country:
United States
Facility:
Name:
City of Hope National Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Facility:
Name:
Keck School of Medicine of the University of Southern California
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Facility:
Name:
Rocky Mountain Cancer Center - Aurora
Address:
City:
Aurora
Zip:
80012
Country:
United States
Facility:
Name:
University of Colorado
Address:
City:
Denver
Zip:
80220
Country:
United States
Facility:
Name:
Medical Oncology Hematology Consultants
Address:
City:
Newark
Zip:
19713
Country:
United States
Facility:
Name:
Florida Cancer Specialists and Research Institute - Lake Mary
Address:
City:
Lake Mary
Zip:
32746
Country:
United States
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48084
Country:
United States
Facility:
Name:
Atlantic Health System - Morristown Medical Center
Address:
City:
Morristown
Zip:
07960
Country:
United States
Facility:
Name:
Weill Cornell Medical College
Address:
City:
New York
Zip:
10021
Country:
United States
Facility:
Name:
Mount Sinai Hospital - New York
Address:
City:
New York
Zip:
10029
Country:
United States
Facility:
Name:
Memorial Sloan Kettering
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
Cleveland Clinic
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Facility:
Name:
Earle A. Chiles Research Institute - Robert W. Franz Cancer Center - Providence Cancer Institute
Address:
City:
Portland
Zip:
97213
Country:
United States
Facility:
Name:
Oregon Health & Science University (OHSU)
Address:
City:
Portland
Zip:
97239
Country:
United States
Facility:
Name:
Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island)
Address:
City:
East Providence
Zip:
02915
Country:
United States
Facility:
Name:
Tennessee Oncology Nashville (Sarah Cannon)
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
Vanderbilt University School of Medicine
Address:
City:
Nashville
Zip:
37215
Country:
United States
Facility:
Name:
Texas Oncology - Austin Midtown
Address:
City:
Austin
Zip:
78705
Country:
United States
Facility:
Name:
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Address:
City:
Dallas
Zip:
75246
Country:
United States
Facility:
Name:
MDACC
Address:
City:
Houston
Zip:
77030
Country:
United States
Facility:
Name:
Virginia Cancer Specialists/NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Facility:
Name:
Swedish Cancer Institute
Address:
City:
Seattle
Zip:
98104
Country:
United States
Facility:
Name:
Northwest Cancer Center Specialists - Vancouver Cancer Center - Compass Oncology Vancouver
Address:
City:
Vancouver
Zip:
98684
Country:
United States
Facility:
Name:
Antwerp University Hospital (UZA)
Address:
City:
Edegem
Zip:
2650
Country:
Belgium
Facility:
Name:
Universitair Ziekenhuis Leuven
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Facility:
Name:
Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho
Address:
City:
Jaú
Zip:
17210-080
Country:
Brazil
Facility:
Name:
Hospital Sirio Libanes Brasilia
Address:
City:
Brasília
Zip:
70200-730
Country:
Brazil
Facility:
Name:
Oncosite - Centro de Pesquisa Clinica Em Oncologia
Address:
City:
Ijuí
Zip:
98700-000
Country:
Brazil
Facility:
Name:
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa
Address:
City:
Porto Alegre
Zip:
90110-270
Country:
Brazil
Facility:
Name:
Instituto Sul Mineiro de Oncologia - ONCOMINAS
Address:
City:
Pouso Alegre
Zip:
37554-216
Country:
Brazil
Facility:
Name:
Instituto Americas
Address:
City:
Rio de Janeiro
Zip:
22775-001
Country:
Brazil
Facility:
Name:
Hospital A.C. Camargo Cancer Center
Address:
City:
São Paulo
Zip:
01509-010
Country:
Brazil
Facility:
Name:
Centro Paulista de Oncologia
Address:
City:
São Paulo
Zip:
04538-132
Country:
Brazil
Facility:
Name:
Service d'Oncologie Medicale - CHRU Besancon
Address:
City:
Besançon
Zip:
25000
Country:
France
Facility:
Name:
Institut Paoli-Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Facility:
Name:
Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University)
Address:
City:
Paris
Zip:
75012
Country:
France
Facility:
Name:
CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
Address:
City:
Poitiers
Zip:
86000
Country:
France
Facility:
Name:
Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris
Address:
City:
Villejuif
Zip:
94805
Country:
France
Facility:
Name:
High Technology Hospital Medcenter Ltd
Address:
City:
Batumi
Zip:
0144
Country:
Georgia
Facility:
Name:
Innova LLC
Address:
City:
Tbilisi
Zip:
0159
Country:
Georgia
Facility:
Name:
Tbilisi Central Hospital Ltd
Address:
City:
Tbilisi
Zip:
0159
Country:
Georgia
Facility:
Name:
Fondazione IRCCS Instituto Nazionale dei Tumori
Address:
City:
Milano
Zip:
20133
Country:
Italy
Facility:
Name:
ASST Grande Ospedale Metropolitano Niguarda
Address:
City:
Milano
Zip:
20162
Country:
Italy
Facility:
Name:
Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera
Address:
City:
Padova
Zip:
35128
Country:
Italy
Facility:
Name:
Regional State Budgetary Institution of Healthcare"Altai Regional Oncology Dispensary"
Address:
City:
Barnaul
Zip:
656045
Country:
Russian Federation
Facility:
Name:
Limited Liability Company "EVIMED"
Address:
City:
Chelyabinsk
Zip:
454048
Country:
Russian Federation
Facility:
Name:
State Budgetary Institution of Health Care "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar region
Address:
City:
Krasnodar
Zip:
350040
Country:
Russian Federation
Facility:
Name:
Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G. E. Ostroverkhov"
Address:
City:
Kursk
Zip:
305524
Country:
Russian Federation
Facility:
Name:
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"
Address:
City:
Moscow
Zip:
111123
Country:
Russian Federation
Facility:
Name:
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
Address:
City:
Moscow
Zip:
119991
Country:
Russian Federation
Facility:
Name:
Branch office of " Hadassah Medical Ltd"
Address:
City:
Moscow
Zip:
121205
Country:
Russian Federation
Facility:
Name:
Closed Joint Stock Company Medical Center "AVICENNA"
Address:
City:
Novosibirsk
Zip:
630099
Country:
Russian Federation
Facility:
Name:
BHI of the Omsk region "Clinical oncological dispensary"
Address:
City:
Omsk
Zip:
644013
Country:
Russian Federation
Facility:
Name:
"Clinical Hospital "RZD-Medicine" of Saint Petersburg"
Address:
City:
Saint Petersburg
Zip:
195271
Country:
Russian Federation
Facility:
Name:
Federal State Budgetary Institution "National Medical Research Center of Oncology named after N.N.Petrov" of the Ministry of Health of the Russian Federation
Address:
City:
Saint Petersburg
Zip:
197758
Country:
Russian Federation
Facility:
Name:
Napalkov SBHI "Saint-Petersburg clinical scientific and practical center for specialised types of medical care (oncological)
Address:
City:
Saint Petersburg
Zip:
197758
Country:
Russian Federation
Facility:
Name:
Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
Address:
City:
Saint Petersburg
Country:
Russian Federation
Facility:
Name:
Siberian State Medical University
Address:
City:
Tomsk
Zip:
634028
Country:
Russian Federation
Facility:
Name:
Vall d'Hebron Institute of Oncology (VHIO)
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Facility:
Name:
Clínica Universidad de Navarra - Sede Madrid
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Facility:
Name:
Clínica Universidad de Navarra - Sede Pamplona
Address:
City:
Pamplona
Zip:
31008
Country:
Spain
Facility:
Name:
Hospital Universitario Marques de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Start date:
November 30, 2022
Completion date:
July 2025
Lead sponsor:
Agency:
Agenus Inc.
Agency class:
Industry
Source:
Agenus Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05608044
