Program Status
Active, not recruitingPhase
Phase 2Prior Immunotherapy Allowed
NoCRC-directed Trial
YesDrugs
Balstilimab, Botensilimab, Regorafenib, TAS-102Tags
MSS/ MMRpComments
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
Helpful Links
https://meetings.asco.org/abstracts-presentations/216505Location | 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.