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

Sponsor

Agenus Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05608044

Collaborator

(none)

230

Enrollment

Locations

Arms

Anticipated Duration (Months)

5.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: Botensilimab Drug: Balstilimab Drug: Standard of Care	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

230 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 30, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination Botensilimab Dose 1 plus Balstilimab Participants will receive botensilimab at dose 1 given IV and balstilimab given IV.	Drug: Botensilimab An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody. Other Names: AGEN1181 Drug: Balstilimab An anti-programmed death (ligand) 1 [PD-(L)1] monoclonal antibody. Other Names: AGEN2034
Experimental: Combination Botensilimab Dose 2 plus Balstilimab Participants will receive botensilimab at dose 2 given IV and balstilimab given IV.	Drug: Botensilimab An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody. Other Names: AGEN1181 Drug: Balstilimab An anti-programmed death (ligand) 1 [PD-(L)1] monoclonal antibody. Other Names: AGEN2034
Experimental: Monotherapy Botensilimab Dose 1 Participants will receive botensilimab dose 1 given IV.	Drug: Botensilimab An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody. Other Names: AGEN1181
Experimental: Monotherapy Botensilimab Dose 2 Participants will receive botensilimab dose 2 given IV.	Drug: Botensilimab An anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody. Other Names: AGEN1181
Active Comparator: Standard of Care Participants will receive select standard of care as determined by the investigator.	Drug: Standard of Care Regorafenib or trifluridine and tipiracil.

Outcome Measures

Primary Outcome Measures

Objective Response Rate [First dose through up to 2 years]
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).

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Standard chemotherapy including all of the following agents (if eligible and with no contraindication): fluoropyrimidine, irinotecan, oxaliplatin, and an anti-epidermal growth factor receptor antibody (cetuximab or panitumumab) 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 (within 72 hours of first dose of study treatment) 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 trial, starting with the Screening visit through 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Exclusion Criteria:

Tumor is MSI-H/dMMR per a standard local testing method.
Received PD-(L)1 and 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: With certain exceptions, participants with definitively treated liver metastases (this includes surgical resection 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.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster < 7 days before C1D1.
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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute	Scottsdale	Arizona	United States	85258
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	Keck School of Medicine of the University of Southern California	Los Angeles	California	United States	90033
4	Rocky Mountain Cancer Center - Aurora	Aurora	Colorado	United States	80012
5	University of Colorado	Denver	Colorado	United States	80220
6	Medical Oncology Hematology Consultants	Newark	Delaware	United States	19713
7	Florida Cancer Specialists and Research Institute - Lake Mary	Lake Mary	Florida	United States	32746
8	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
11	University of Michigan	Ann Arbor	Michigan	United States	48084
12	Atlantic Health System - Morristown Medical Center	Morristown	New Jersey	United States	07960
13	Weill Cornell Medical College	New York	New York	United States	10021
14	Mount Sinai Hospital - New York	New York	New York	United States	10029
15	Memorial Sloan Kettering	New York	New York	United States	10065
16	Cleveland Clinic	Cleveland	Ohio	United States	44195
17	Earle A. Chiles Research Institute - Robert W. Franz Cancer Center - Providence Cancer Institute	Portland	Oregon	United States	97213
18	Oregon Health & Science University (OHSU)	Portland	Oregon	United States	97239
19	Lifespan Clinical Research Center/Cancer Institute (Providence Rhode Island)	East Providence	Rhode Island	United States	02915
20	Tennessee Oncology Nashville (Sarah Cannon)	Nashville	Tennessee	United States	37203
21	Vanderbilt University School of Medicine	Nashville	Tennessee	United States	37215
22	Texas Oncology - Austin Midtown	Austin	Texas	United States	78705
23	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
24	MDACC	Houston	Texas	United States	77030
25	Virginia Cancer Specialists/ NEXT Virginia	Fairfax	Virginia	United States	22031
26	Swedish Cancer Institute	Seattle	Washington	United States	98104
27	Antwerp University Hospital (UZA)	Edegem		Belgium	2650
28	Universitair Ziekenhuis Leuven	Leuven		Belgium	3000
29	Service d'Oncologie Medicale - CHRU Besancon	Besançon		France	25000
30	Centre Georges Francois Leclerc	Dijon		France	21079
31	Hôpital Saint Antoine/AP-HP Hopital Saint Antoine (Pierre and Marie Curie University)	Paris		France	75012
32	CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)	Poitiers		France	86000
33	Unversite Paris-Saclay Gustave Roussy Cancer Center Campus Paris	Villejuif		France	94805
34	IRCCS Azienda Ospedaliera Universitaria San Martino IST	Genova		Italy	16132
35	Fondazione IRCCS Instituto Nazionale dei Tumori	Milano		Italy	20133
36	ASST Grande Ospedale Metropolitano Niguarda	Milano		Italy	20162
37	Istituto Oncologico Veneto	Padova		Italy	35128
38	Azienda Ospedaliero Universitaria Pisana - Stabilimento di Santa Chiara	Pisa		Italy	56126
39	Vall d'Hebron Institute of Oncology (VHIO)	Barcelona		Spain	8035
40	Clínica Universidad de Navarra - Sede Madrid	Madrid		Spain	28027
41	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
42	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008