Botensilimab and Balstilimab Optimization in Colorectal Cancer

NCT06268015 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Pro00115311
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Disease control rate based on iRECIST at second restaging scan

  Disease control rate is defined as the proportion of subjects who have a complete response, partial response, or stable disease at the time of a second restaging scan. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease is defined as a decrease of less than 30% or an increase of less than 20%. Increases of 20% or greater must be confirmed 4-8 weeks later, and confirmation scans must also show an increase of at least 5 mm in the sum of lesion sizes or an increase in the number of lesions. Otherwise, the increase will be counted as stable disease.

  24 weeks after screening

• Proportion of subjects with a best overall response of complete response or partial response according to iRECIST

  The number of subjects who went on treatment and had a complete response or partial response sometime during the study (prior to progression) divided by the number of subjects who went on treatment.

  up to 2 years

Secondary Outcomes (4)

• Disease control rate based on RECIST v1.1 at second restaging scan

  24 weeks after screening

• Proportion of subjects with a best overall response of complete response or partial response according to RECIST v1.1

  up to 2 years

• Months of overall survival

  up to 2 years

• Months of progression-free survival

  up to 2 years

Study Arms (1)

Treatment

EXPERIMENTAL

botensilimab + balstilimab until disease progression, then botensilimab + balstilimab + mFOLFOX6 (leucovorin, fluorouracil, oxaliplatin) + {bevacizumab or panitumumab}

Drug: Botensilimab; Drug: Balstilimab; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Drug: Bevacizumab; Drug: Panitumumab

Interventions

Bevacizumab DRUG

5 mg/kg IV every 2 weeks

Treatment

Panitumumab DRUG

6 mg/kg IV every 2 weeks

Treatment

Botensilimab DRUG

75 mg IV every 6 weeks for up to 4 doses

Treatment

Balstilimab DRUG

240 mg IV every 2 weeks

Treatment

Oxaliplatin DRUG

85 mg/m2 IV every 2 weeks

Treatment

Leucovorin DRUG

400 mg/m2 IV every 2 weeks

Treatment

Fluorouracil DRUG

400 mg/m2 IV bolus + 2,400 mg/m2 IV (over 46 hours) every 2 weeks

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants of any gender who are at least 18 years of age on the day of signing informed consent.
• Histologically confirmed metastatic and/or unresectable colorectal cancer without liver metastasis or known or suspected bone or brain metastases.
• 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.
• 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.
• ECOG performance status of 0 or 1.
• No prior systemic therapy for colon cancer.
• a. Subjects who received systemic therapy in the neoadjuvant or adjuvant setting completed at least 6 months prior to enrollment are eligible.
• Measurable disease per RECIST v1.1.
• People of child-bearing potential must not be pregnant or breast feeding and meet at least one of the following conditions:
• Not a person of childbearing potential (POCBP)
• 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.
• All participants must practice effective contraceptive methods (refer to section 6.7.1) during the treatment period, unless documentation of infertility exists.
• Expected to survive \>3 months per investigator assessment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Adequate organ function as defined below. Specimens must have been collected within 7 days prior to the start of study treatment:

You may not qualify if:

• Prior therapy with an immune checkpoint inhibitor.
• A POCBP who is pregnant or breastfeeding or has a positive pregnancy test within 72 hours prior to receiving study treatment
• Not willing to use an effective method of birth control as defined in section 6.7.1
• Known liver, bone, or CNS metastases and/or carcinomatous meningitis.
• 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.
• 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.
• Any history of chronic or autoimmune pancreatitis.
• Known history of or any evidence of active, non-infectious pneumonitis.
• Current use of medications specified by the protocol as prohibited for administration in combination with study drug.
• 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.
• Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Corticosteroids administered as pre-medication for IV contrast allergy are also allowed.
• Received a live vaccine within 30 days prior to the start of study drug.
• 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
• COVID-19 vaccines will be allowed. However, COVID vaccines are not allowed within 7 days of starting study drug treatment

Sponsors & Collaborators

• Nicholas DeVito, MD: lead
• Gateway for Cancer Research: collaborator
• Agenus Inc.: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

balstilimab; Oxaliplatin; Leucovorin; Fluorouracil; Bevacizumab; Panitumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 20, 2024
• Study Start: November 18, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)