ACTIVE_NOT_RECRUITING

Botensilimab and Balstilimab Optimization in Colorectal Cancer

Conditions

Colorectal Cancer metastatic unresectable microsatellite stable MSS untreated first-line 1st line

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a single-arm, interventional, pilot clinical trial. Fifteen evaluable patients will have tumor-informed ctDNA testing at baseline and start botensilimab and balstilimab treatment. They will receive botensilimab and balstilimab in 6-week cycles until progression, after which mFOLFOX6 and bevacizumab or panitumumab will be added to the regimen. Subjects will have safety testing at baseline and every two weeks while on study drug. Study treatment with botensilimab and balstilimab, mFOLFOX6, and bevacizumab or panitumumab will be continued until radiographic or clinical progression, toxicity, or patient withdrawal. Subjects will have one safety follow up visit 30 days after the last treatment and will be followed for survival every 12 weeks for up to 2 years.

Official Title

Botensilimab and Balstilimab Optimization in Colorectal Cancer (BBOpCo)

Quick Facts

Study Start:2024-11-18

Study Completion:2028-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06268015

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants of any gender who are at least 18 years of age on the day of signing informed consent. 2. Histologically confirmed metastatic and/or unresectable colorectal cancer without liver metastasis or known or suspected bone or brain metastases. 3. Microsatellite stable disease, as documented in the participant's medical record at the time of consent by the absence of MSI-H or dMMR result in an FDA-approved assay or an IVD offered as an LDT that includes microsatellite stability biomarker. 4. Subject must be willing to provide fresh biopsy of tumor lesion. \Note: Those who do not have a tumor lesion that is safe and amenable to biopsy may still be enrolled. 5. ECOG performance status of 0 or 1. 6. No prior systemic therapy for colon cancer. 7. Measurable disease per RECIST v1.1. 8. People of child-bearing potential must not be pregnant or breast feeding and meet at least one of the following conditions: 1. Not a person of childbearing potential (POCBP) 2. A POCBP must agree to use a reliable method of contraception (refer to Section 6.7.1) during the treatment period and for at least 180 days after the last dose of study treatment. 9. All participants must practice effective contraceptive methods (refer to section 6.7.1) during the treatment period, unless documentation of infertility exists. 10. Expected to survive \>3 months per investigator assessment. 11. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial 12. Adequate organ function as defined below. Specimens must have been collected within 7 days prior to the start of study treatment: Absolute neutrophil count (ANC) ≥1,500/µL * Platelets ≥100,000/µL * Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within the last 2 weeks) * Measured or calculated creatinine clearance (GFR can be used in place of CrCl) ≥45 mL/min (Creatinine clearance (CrCl) should be calculated per institutional standard) * Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \> 1.5 x ULN * AST (SGOT) and ALT (SGPT) ≤2.5 x ULN * International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants	1. Prior therapy with an immune checkpoint inhibitor. 2. A POCBP who is pregnant or breastfeeding or has a positive pregnancy test within 72 hours prior to receiving study treatment 3. Not willing to use an effective method of birth control as defined in section 6.7.1 4. Known liver, bone, or CNS metastases and/or carcinomatous meningitis. 5. Diagnosis of other carcinomas within the last 2 years, except cured non-melanoma skin cancer, treated thyroid cancer, curatively treated in-situ cervical cancer, or localized prostate cancer treated curatively with no evidence of biochemical or imaging recurrence. 6. Documented history of clinically significant autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, type 1 diabetes mellitus, psoriasis not requiring systemic treatment, well-controlled hypothyroidism, or conditions not expected to recur in the absence of and external trigger are permitted to enroll. 7. Any history of chronic or autoimmune pancreatitis. 8. Known history of or any evidence of active, non-infectious pneumonitis. 9. Current use of medications specified by the protocol as prohibited for administration in combination with study drug. 1. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the start of study drug are not eligible. 2. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 3. Corticosteroids administered as pre-medication for IV contrast allergy are also allowed. 10. Received a live vaccine within 30 days prior to the start of study drug. 1. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (e.g. Flu-Mist) are live-attenuated vaccines, and are not allowed within 28 days of study treatment 2. COVID-19 vaccines will be allowed. However, COVID vaccines are not allowed within 7 days of starting study drug treatment 11. Recent or current active infectious disease requiring systemic antivirals, antibiotics or antifungals, or treatment within 2 weeks prior to the start of study drug. 12. Concurrent severe and/or uncontrolled medical conditions, which may compromise participation in the study, including impaired heart function or clinically significant heart disease. 13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the start of study drug (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study. 14. Serious, non-healing wound, ulcer, or bone fracture. 15. Patients with a history of organ or allogenic hematopoietic stem cell transplantation. 16. Partial or complete bowel obstruction within the last 3 months, signs/ symptoms of bowel obstruction, or known radiologic evidence of impeding obstruction. 17. Refractory ascites defined as requiring 2 or more therapeutic paracenteses within the last 4 weeks or ≥4 times within the last 90 days or ≥1 time within the last 2 weeks prior to study entry or requiring diuretics within 2 weeks of study entry. 18. Tumor location or size that may result in life-threatening complications. For example, lesions that may put patient at risk for intestinal perforation or obstruction. 19. Known or suspected allergy or hypersensitivity to any investigational or standard of care therapy agents, or any of the inactive ingredients in any of the components of the study drug regimen. 20. Peripheral neuropathy from prior neoadjuvant or adjuvant oxaliplatin must have resolved to G2 or lower.

Inclusion Criteria

Exclusion Criteria

1. Participants of any gender who are at least 18 years of age on the day of signing informed consent.
2. Histologically confirmed metastatic and/or unresectable colorectal cancer without liver metastasis or known or suspected bone or brain metastases.
3. Microsatellite stable disease, as documented in the participant's medical record at the time of consent by the absence of MSI-H or dMMR result in an FDA-approved assay or an IVD offered as an LDT that includes microsatellite stability biomarker.
4. Subject must be willing to provide fresh biopsy of tumor lesion. \*Note: Those who do not have a tumor lesion that is safe and amenable to biopsy may still be enrolled.
5. ECOG performance status of 0 or 1.
6. No prior systemic therapy for colon cancer.
7. Measurable disease per RECIST v1.1.
8. People of child-bearing potential must not be pregnant or breast feeding and meet at least one of the following conditions:
1. Not a person of childbearing potential (POCBP)
2. A POCBP must agree to use a reliable method of contraception (refer to Section 6.7.1) during the treatment period and for at least 180 days after the last dose of study treatment.
9. All participants must practice effective contraceptive methods (refer to section 6.7.1) during the treatment period, unless documentation of infertility exists.
10. Expected to survive \>3 months per investigator assessment.
11. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
12. Adequate organ function as defined below. Specimens must have been collected within 7 days prior to the start of study treatment:
* Absolute neutrophil count (ANC) ≥1,500/µL
* Platelets ≥100,000/µL
* Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within the last 2 weeks)
* Measured or calculated creatinine clearance (GFR can be used in place of CrCl) ≥45 mL/min (Creatinine clearance (CrCl) should be calculated per institutional standard)
* Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \> 1.5 x ULN
* AST (SGOT) and ALT (SGPT) ≤2.5 x ULN
* International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants

1. Prior therapy with an immune checkpoint inhibitor.
2. A POCBP who is pregnant or breastfeeding or has a positive pregnancy test within 72 hours prior to receiving study treatment
3. Not willing to use an effective method of birth control as defined in section 6.7.1
4. Known liver, bone, or CNS metastases and/or carcinomatous meningitis.
5. Diagnosis of other carcinomas within the last 2 years, except cured non-melanoma skin cancer, treated thyroid cancer, curatively treated in-situ cervical cancer, or localized prostate cancer treated curatively with no evidence of biochemical or imaging recurrence.
6. Documented history of clinically significant autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, type 1 diabetes mellitus, psoriasis not requiring systemic treatment, well-controlled hypothyroidism, or conditions not expected to recur in the absence of and external trigger are permitted to enroll.
7. Any history of chronic or autoimmune pancreatitis.
8. Known history of or any evidence of active, non-infectious pneumonitis.
9. Current use of medications specified by the protocol as prohibited for administration in combination with study drug.
1. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the start of study drug are not eligible.
2. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
3. Corticosteroids administered as pre-medication for IV contrast allergy are also allowed.
10. Received a live vaccine within 30 days prior to the start of study drug.
1. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (e.g. Flu-Mist) are live-attenuated vaccines, and are not allowed within 28 days of study treatment
2. COVID-19 vaccines will be allowed. However, COVID vaccines are not allowed within 7 days of starting study drug treatment
11. Recent or current active infectious disease requiring systemic antivirals, antibiotics or antifungals, or treatment within 2 weeks prior to the start of study drug.
12. Concurrent severe and/or uncontrolled medical conditions, which may compromise participation in the study, including impaired heart function or clinically significant heart disease.
13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the start of study drug (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study.
14. Serious, non-healing wound, ulcer, or bone fracture.
15. Patients with a history of organ or allogenic hematopoietic stem cell transplantation.
16. Partial or complete bowel obstruction within the last 3 months, signs/ symptoms of bowel obstruction, or known radiologic evidence of impeding obstruction.
17. Refractory ascites defined as requiring 2 or more therapeutic paracenteses within the last 4 weeks or ≥4 times within the last 90 days or ≥1 time within the last 2 weeks prior to study entry or requiring diuretics within 2 weeks of study entry.
18. Tumor location or size that may result in life-threatening complications. For example, lesions that may put patient at risk for intestinal perforation or obstruction.
19. Known or suspected allergy or hypersensitivity to any investigational or standard of care therapy agents, or any of the inactive ingredients in any of the components of the study drug regimen.
20. Peripheral neuropathy from prior neoadjuvant or adjuvant oxaliplatin must have resolved to G2 or lower.

Contacts and Locations

Study Locations (Sites)

Duke University

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: Nicholas DeVito, MD

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-11-18

Study Completion Date2028-07

Study Record Updates

Study Start Date2024-11-18

Study Completion Date2028-07

Terms related to this study

Keywords Provided by Researchers

metastatic
unresectable
microsatellite stable
MSS
untreated
first-line
1st line

Additional Relevant MeSH Terms

Colorectal Cancer