Clinical trial NCT05608044: A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Official title: A Randomized, Open-Label, Phase 2 Study of Botensilimab (AGEN1181) as Monotherapy and in Combination With Balstilimab (AGEN2034) or Investigator's Choice Standard of Care (Regorafenib or Trifluridine and Tipiracil) for the Treatment of Refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Agenus Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-08
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: First dose through up to 2 years
Secondary outcomes:
measure: Duration of Response
timeFrame: First dose through up to 2 years
measure: Progression-free Survival
timeFrame: First dose through up to 3 years
measure: Overall Survival
timeFrame: First dose through up to 3 years
measure: Number of Participants Experiencing Treatment-emergent Adverse Events
timeFrame: First dose through up to 2 years
measure: Serum Botensilimab Concentration
timeFrame: First study dose (pre-dose and 1 hour post-dose) through up to 2 years
measure: Serum Balstilimab Concentration
timeFrame: First study dose (pre-dose and 1 hour post-dose) through up to 2 years
measure: Number of Participants Positive for Botensilimab Anti-drug Antibodies Following Treatment with Botensilimab
timeFrame: First study dose (pre-dose and 1 hour post-dose) through up to 2 years
measure: Number of Participants Positive for Balstilimab Anti-drug Antibodies Following Treatment with Balstilimab
timeFrame: First study dose (pre-dose and 1 hour post-dose) through up to 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of the University of Southern California
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Center - Aurora
state: Colorado
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants
state: Delaware
city: Lake Mary
country: United States
facility: Florida Cancer Specialists and Research Institute - Lake Mary
state: Florida
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Morristown
country: United States
facility: Atlantic Health System - Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital - New York
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Earle A. Chiles Research Institute - Robert W. Franz Cancer Center - Providence Cancer Institute
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: East Providence
country: United States
facility: Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island)
state: Rhode Island
city: Nashville
country: United States
facility: Tennessee Oncology Nashville (Sarah Cannon)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: MDACC
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists/NEXT Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Center Specialists - Vancouver Cancer Center - Compass Oncology Vancouver
state: Washington
city: Edegem
country: Belgium
facility: Antwerp University Hospital (UZA)
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Jaú
country: Brazil
facility: Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho
state: São Paulo
city: Brasília
country: Brazil
facility: Hospital Sirio Libanes Brasilia
city: Ijuí
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa
city: Pouso Alegre
country: Brazil
facility: Instituto Sul Mineiro de Oncologia - ONCOMINAS
city: Rio de Janeiro
country: Brazil
facility: Instituto Americas
city: São Paulo
country: Brazil
facility: Hospital A.C. Camargo Cancer Center
city: São Paulo
country: Brazil
facility: Centro Paulista de Oncologia
city: Besançon
country: France
facility: Service d'Oncologie Medicale - CHRU Besancon
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Paris
country: France
facility: Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University)
city: Poitiers
country: France
facility: CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
city: Villejuif
country: France
facility: Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris
city: Batumi
country: Georgia
facility: High Technology Hospital Medcenter Ltd
city: Tbilisi
country: Georgia
facility: Innova LLC
city: Tbilisi
country: Georgia
facility: Tbilisi Central Hospital Ltd
city: Milano
country: Italy
facility: Fondazione IRCCS Instituto Nazionale dei Tumori
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Padova
country: Italy
facility: Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera
city: Barnaul
country: Russian Federation
facility: Regional State Budgetary Institution of Healthcare"Altai Regional Oncology Dispensary"
city: Chelyabinsk
country: Russian Federation
facility: Limited Liability Company "EVIMED"
city: Krasnodar
country: Russian Federation
facility: State Budgetary Institution of Health Care "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar region
city: Kursk
country: Russian Federation
facility: Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G. E. Ostroverkhov"
city: Moscow
country: Russian Federation
facility: 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"
city: Moscow
country: Russian Federation
facility: 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
city: Moscow
country: Russian Federation
facility: Branch office of " Hadassah Medical Ltd"
city: Novosibirsk
country: Russian Federation
facility: Closed Joint Stock Company Medical Center "AVICENNA"
city: Omsk
country: Russian Federation
facility: BHI of the Omsk region "Clinical oncological dispensary"
city: Saint Petersburg
country: Russian Federation
facility: "Clinical Hospital "RZD-Medicine" of Saint Petersburg"
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "National Medical Research Center of Oncology named after N.N.Petrov" of the Ministry of Health of the Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: Napalkov SBHI "Saint-Petersburg clinical scientific and practical center for specialised types of medical care (oncological)
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO)
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra - Sede Madrid
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra - Sede Pamplona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
Study officials:
affiliation: Agenus Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: