A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer Without Liver Metastases

Program Status

Active, not recruiting

Phase

Phase 2

Prior Immunotherapy Allowed

No

CRC-directed Trial

Yes

Drugs

Balstilimab, Botensilimab, Regorafenib, TAS-102

Tags

MSS/ MMRp

Comments

Phase 2 trial, only for MSS mCRC. Several locations.
Promising results from phase 1 trial, per GI ASCO 2023 (see below, and Helpful Links).
Experimental agents, two different types of immunotherapy, checkpoint inhibitors: botensilimab and balstilimab (BOT + BAL).
Botensilimab is a next-generation, Fc-enhanced, CTLA-4 inhibitor, and balstilimab is a PD-1 inhibitor.

Five arms, randomized assignation:
1. Experimental: BOT + BAL at dose 1
2. Experimental: BOT + BAL at dose 2 (different dose)
3. Experimental: BOT (Fc-enhanced, CTLA-4 inhibitor) at dose 1
4: Experimental: BOT (Fc-enhanced, CTLA-4 inhibitor) at dose 2
5. Standard of care: regorafenib (Stivarga) or TAS-102 (Lonsurf)

No prior immunotherapy, regorafenib or TAS-102 allowed. Patients with active liver metastases not allowed.

Results from expanded phase 1a/1b study, NCT03860272: The administration of these two immunotherapies resulted in objective response rate (ORR) at 23%, disease control rate at 76%, progression-free survival (PFS) 4.1 months, and the median overall survival has not been reached. (“Response” is a tumor reduction of greater than 30%, with stable disease at +/- 30%). The estimated 12-month overall survival at 63% is better than the current standard of care.

Patients had received a median of four prior lines of therapy, and 59% had RAS mutations. Prior immunotherapy was allowed in this trial.

Most patients (91%) reported immune-related adverse events (irAEs). The most common were diarrhea/colitis (43%) and fatigue (34%). The most common grade 3 irAEs were diarrhea/colitis (20%), fatigue (4%), and pyrexia (raised body temperature) (4%)


Related trials, also in this Trial Finder:
NCT05672316
NCT03860272
NCT05627635

Location Location Status
United States
HonorHealth Research Institute
Scottsdale, Arizona 85258
Active, not recruiting
City of Hope National Medical Center
Duarte, California 91010
Active, not recruiting
Keck School of Medicine of the University of Southern California
Los Angeles, California 90033
Active, not recruiting
Rocky Mountain Cancer Center - Aurora
Aurora, Colorado 80012
Active, not recruiting
University of Colorado
Denver, Colorado 80220
Active, not recruiting
Medical Oncology Hematology Consultants
Newark, Delaware 19713
Active, not recruiting
Florida Cancer Specialists and Research Institute - Lake Mary
Lake Mary, Florida 32746
Active, not recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
Active, not recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
Active, not recruiting
University of Michigan
Ann Arbor, Michigan 48084
Active, not recruiting
Atlantic Health System - Morristown Medical Center
Morristown, New Jersey 07960
Active, not recruiting
Weill Cornell Medical College
New York, New York 10021
Active, not recruiting
Mount Sinai Hospital - New York
New York, New York 10029
Active, not recruiting
Memorial Sloan Kettering
New York, New York 10065
Active, not recruiting
Cleveland Clinic
Cleveland, Ohio 44195
Active, not recruiting
Earle A. Chiles Research Institute - Robert W. Franz Cancer Center - Providence Cancer Institute
Portland, Oregon 97213
Active, not recruiting
Oregon Health & Science University (OHSU)
Portland, Oregon 97239
Active, not recruiting
Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island)
East Providence, Rhode Island 02915
Active, not recruiting
Tennessee Oncology Nashville (Sarah Cannon)
Nashville, Tennessee 37203
Active, not recruiting
Vanderbilt University School of Medicine
Nashville, Tennessee 37215
Active, not recruiting
Texas Oncology - Austin Midtown
Austin, Texas 78705
Active, not recruiting
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas 75246
Active, not recruiting
MDACC
Houston, Texas 77030
Active, not recruiting
Virginia Cancer Specialists/NEXT Virginia
Fairfax, Virginia 22031
Active, not recruiting
Swedish Cancer Institute
Seattle, Washington 98104
Active, not recruiting
Northwest Cancer Center Specialists - Vancouver Cancer Center - Compass Oncology Vancouver
Vancouver, Washington 98684
Active, not recruiting
Belgium
Antwerp University Hospital (UZA)
Edegem 2650
Active, not recruiting
Universitair Ziekenhuis Leuven
Leuven 3000
Active, not recruiting
Brazil
Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho
Jaú, São Paulo 17210-080
Active, not recruiting
Hospital Sirio Libanes Brasilia
Brasília 70200-730
Active, not recruiting
Oncosite - Centro de Pesquisa Clinica Em Oncologia
Ijuí 98700-000
Active, not recruiting
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa
Porto Alegre 90110-270
Active, not recruiting
Instituto Sul Mineiro de Oncologia - ONCOMINAS
Pouso Alegre 37554-216
Active, not recruiting
Instituto Americas
Rio de Janeiro 22775-001
Active, not recruiting
Hospital A.C. Camargo Cancer Center
São Paulo 01509-010
Active, not recruiting
Centro Paulista de Oncologia
São Paulo 04538-132
Active, not recruiting
France
Service d'Oncologie Medicale - CHRU Besancon
Besançon 25000
Active, not recruiting
Institut Paoli-Calmettes
Marseille 13009
Active, not recruiting
Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University)
Paris 75012
Active, not recruiting
CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
Poitiers 86000
Active, not recruiting
Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris
Villejuif 94805
Active, not recruiting
Georgia
High Technology Hospital Medcenter Ltd
Batumi 0144
Active, not recruiting
Innova LLC
Tbilisi 0159
Active, not recruiting
Tbilisi Central Hospital Ltd
Tbilisi 0159
Active, not recruiting
Italy
Fondazione IRCCS Instituto Nazionale dei Tumori
Milano 20133
Active, not recruiting
ASST Grande Ospedale Metropolitano Niguarda
Milano 20162
Active, not recruiting
Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera
Padova 35128
Active, not recruiting
Russian Federation
Regional State Budgetary Institution of Healthcare"Altai Regional Oncology Dispensary"
Barnaul 656045
Active, not recruiting
Limited Liability Company "EVIMED"
Chelyabinsk 454048
Active, not recruiting
State Budgetary Institution of Health Care "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar region
Krasnodar 350040
Active, not recruiting
Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G. E. Ostroverkhov"
Kursk 305524
Active, not recruiting
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
Active, not recruiting
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
Active, not recruiting
Branch office of " Hadassah Medical Ltd"
Moscow 121205
Active, not recruiting
Closed Joint Stock Company Medical Center "AVICENNA"
Novosibirsk 630099
Active, not recruiting
BHI of the Omsk region "Clinical oncological dispensary"
Omsk 644013
Active, not recruiting
"Clinical Hospital "RZD-Medicine" of Saint Petersburg"
Saint Petersburg 195271
Active, not recruiting
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
Active, not recruiting
Napalkov SBHI "Saint-Petersburg clinical scientific and practical center for specialised types of medical care (oncological)
Saint Petersburg 197758
Active, not recruiting
Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
Saint Petersburg
Active, not recruiting
Siberian State Medical University
Tomsk 634028
Active, not recruiting
Spain
Vall d'Hebron Institute of Oncology (VHIO)
Barcelona 8035
Active, not recruiting
Clínica Universidad de Navarra - Sede Madrid
Madrid 28027
Active, not recruiting
Clínica Universidad de Navarra - Sede Pamplona
Pamplona 31008
Active, not recruiting
Hospital Universitario Marques de Valdecilla
Santander 39008
Active, not recruiting

Inclusion Criteria

Inclusion Criteria:

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.

Exclusion Criteria

Exclusion Criteria:

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.
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.

NCT ID

NCT05608044

Date Trial Added

2022-11-08

Updated Date

2024-06-04