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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05608044
• Other study ID #: C-800-25
• Secondary ID: 2022-501546-29
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 30, 2022
• Est. completion date: July 2025

Study information

• Verified date: June 2024
• Source: Agenus Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 234
• Est. completion date: July 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Botensilimab
An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody.
• Balstilimab
An anti-programmed death (ligand) 1 [PD-(L)1] monoclonal antibody.
• Standard of Care
Regorafenib or trifluridine and tipiracil.

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital (UZA)	Edegem
Belgium	Universitair Ziekenhuis Leuven	Leuven
Brazil	Hospital Sirio Libanes Brasilia	Brasília
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia	Ijuí
Brazil	Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho	Jaú	São Paulo
Brazil	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
France	Service d'Oncologie Medicale - CHRU Besancon	Besançon
France	Institut Paoli-Calmettes	Marseille
France	Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University)	Paris
France	CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)	Poitiers
France	Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris	Villejuif
Georgia	High Technology Hospital Medcenter Ltd	Batumi
Georgia	Innova LLC	Tbilisi
Georgia	Tbilisi Central Hospital Ltd	Tbilisi
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Fondazione IRCCS Instituto Nazionale dei Tumori	Milano
Italy	Istituto Oncologico Veneto-I.R.C.C.S. - Ospedale Busonera	Padova
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	Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G. E. Ostroverkhov"	Kursk
Russian Federation	Branch office of " Hadassah Medical Ltd"	Moscow
Russian Federation	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	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	Closed Joint Stock Company Medical Center "AVICENNA"	Novosibirsk
Russian Federation	BHI of the Omsk region "Clinical oncological dispensary"	Omsk
Russian Federation	"Clinical Hospital "RZD-Medicine" of Saint Petersburg"	Saint Petersburg
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	Saint-Petersburg Clinical Research Center of Specialized Types of Medical Care (Oncology)	Saint Petersburg
Russian Federation	Siberian State Medical University	Tomsk
Spain	Vall d'Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Clínica Universidad de Navarra - Sede Madrid	Madrid
Spain	Clínica Universidad de Navarra - Sede Pamplona	Pamplona
Spain	Hospital Universitario Marques de Valdecilla	Santander
United States	University of Michigan	Ann Arbor	Michigan
United States	Rocky Mountain Cancer Center - Aurora	Aurora	Colorado
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	University of Colorado	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island)	East Providence	Rhode Island
United States	Virginia Cancer Specialists/NEXT Virginia	Fairfax	Virginia
United States	MDACC	Houston	Texas
United States	Florida Cancer Specialists and Research Institute - Lake Mary	Lake Mary	Florida
United States	Keck School of Medicine of the University of Southern California	Los Angeles	California
United States	Atlantic Health System - Morristown Medical Center	Morristown	New Jersey
United States	Tennessee Oncology Nashville (Sarah Cannon)	Nashville	Tennessee
United States	Vanderbilt University School of Medicine	Nashville	Tennessee
United States	Memorial Sloan Kettering	New York	New York
United States	Mount Sinai Hospital - New York	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Medical Oncology Hematology Consultants	Newark	Delaware
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	HonorHealth Research Institute	Scottsdale	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	Northwest Cancer Center Specialists - Vancouver Cancer Center - Compass Oncology Vancouver	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Agenus Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  France,  Georgia,  Italy,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	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).	First dose through up to 2 years
Secondary	Duration of Response	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.	First dose through up to 2 years
Secondary	Progression-free Survival	Progression-free survival is defined as the time from randomization until disease progression or death, whichever occurs first, as assessed using RECIST 1.1.	First dose through up to 3 years
Secondary	Overall Survival	Overall survival is defined as the time from randomization until death due to any cause.	First dose through up to 3 years
Secondary	Number of Participants Experiencing Treatment-emergent Adverse Events		First dose through up to 2 years
Secondary	Serum Botensilimab Concentration		First study dose (pre-dose and 1 hour post-dose) through up to 2 years
Secondary	Serum Balstilimab Concentration		First study dose (pre-dose and 1 hour post-dose) through up to 2 years
Secondary	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
Secondary	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