Botensilimab, Balstilimab and Regorafenib or Botensilimab and Balstilimab for the Treatment of Advanced or Metastatic Microsatellite Stable Colorectal Cancer

NCT06575725 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: 24074NCI-2024-06706P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well the combination of botensilimab, balstilimab and regorafenib works compared to botensilimab and balstilimab in treating patients with microsatellite stable colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Regorafenib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps to slow or stop the spread of tumor cells. The combination of botensilimab, balstilimab and regorafenib or botensilimab and balstilimab may be a safe and effective treatment for advanced or metastatic microsatellite stable colorectal cancer.

Conditions

Advanced Colon Adenocarcinoma; Advanced Colorectal Adenocarcinoma; Advanced Rectal Adenocarcinoma; Metastatic Colon Adenocarcinoma; Metastatic Colorectal Adenocarcinoma; Metastatic Rectal Adenocarcinoma; Stage III Colon Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8; Stage IV Colon Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Rectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (4)

• Incidence of dose limiting toxicities (Safety lead in)

  Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  During cycle 1 (42 days)

• Treatment related adverse event rates (Safety lead in)

  Assessed by NCI CTCAE version 5.0.

  During cycle 1 (42 days)

• Response rate (Phase II) RECIST

  Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (primary) in microsatellite stable metastatic colorectal cancer patients without metastatic liver lesions receiving botensilimab, balstilimab and regorafenib versus botensilimab and balstilimab, by treatment arm. Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals.

  Up to 5 years after completion of study treatment

• Response rate (Phase II) Immune-Modified RECIST

  Assessed by Immune-Modified RECIST (secondary) in microsatellite stable metastatic colorectal cancer patients without metastatic liver lesions receiving botensilimab, balstilimab and regorafenib versus botensilimab and balstilimab, by treatment arm. Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals.

  Up to 5 years after completion of study treatment

Secondary Outcomes (4)

• Overall survival

  From enrollment to death as a result of any cause or being censored at their last contact, assessed up to 5 years after completion of study treatment

• Progression free survival

  From enrollment to disease progression/relapse or death as a result of any cause, whichever occurs first, assessed up to 5 years after completion of study treatment

• Duration of treatment response

  Up to 5 years after completion of study treatment

• Incidence of adverse events

  Up to 90 days after completion of study treatment

Study Arms (2)

Arm BB (botensilimab, balstilimab)

EXPERIMENTAL

Patients receive botensilimab IV over 60 minutes on day 1 of each cycle and balstilimab IV over 30 minutes on days 1, 15, and 29 of each cycle. Cycles repeat every 42 days for up to 2 cycles of botensilimab and up to 2 years of balstilimab in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the trial. Patients also undergo tumor biopsy during screening and on study.

Biological: Balstilimab; Procedure: Biopsy; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Arm BBR (botensilimab, balstilimab, regorafenib)

EXPERIMENTAL

Patients receive botensilimab IV over 60 minutes on day 1 of each cycle, balstilimab IV over 30 minutes on days 1, 15, and 29 of each cycle, and regorafenib PO QD on days 1-7, 15-21, and 29-35 of each cycle or on days 1-5, 15-19, and 29-33 of each cycle. Cycles repeat every 42 days for up to 2 cycles of botensilimab and up to 2 years of balstilimab and regorafenib in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI and blood sample collection throughout the trial. Patients also undergo tumor biopsy during screening and on study.

Biological: Balstilimab; Procedure: Biopsy; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Regorafenib

Interventions

Balstilimab BIOLOGICAL

Given IV

Also known as: AGEN 2034, AGEN-2034, AGEN2034

Arm BB (botensilimab, balstilimab); Arm BBR (botensilimab, balstilimab, regorafenib)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Arm BB (botensilimab, balstilimab); Arm BBR (botensilimab, balstilimab, regorafenib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm BB (botensilimab, balstilimab); Arm BBR (botensilimab, balstilimab, regorafenib)

Botensilimab BIOLOGICAL

Given IV

Also known as: AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181

Arm BB (botensilimab, balstilimab); Arm BBR (botensilimab, balstilimab, regorafenib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Arm BB (botensilimab, balstilimab); Arm BBR (botensilimab, balstilimab, regorafenib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm BB (botensilimab, balstilimab); Arm BBR (botensilimab, balstilimab, regorafenib)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506 Monohydrate, BAY-73-4506 Monohydrate, Regorafenib Monohydrate, Stivarga

Arm BBR (botensilimab, balstilimab, regorafenib)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant
• In the phase II randomized portion of the study only, until two biopsies are obtained on ten patients receiving BBR and ten patients receiving BB: Agreement to biopsy of the same tumor at baseline and at 4 weeks
• Agreement to biopsy of the same tumor at baseline and at 4 weeks
• This applies only to patients with easily accessible tumors, where the risk of a biopsy is deemed acceptable. If a biopsy is determined to be unsafe patients will be exempt from this requirement
• Agreement to allow the collection of blood for correlatives at baseline, 1 week, 2 weeks, 4 weeks, 8 weeks, and at the time progressive disease
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Histologically or cytologically confirmed advanced or metastatic progressive proficient mismatch repair (pMMR)/MSS adenocarcinoma of the colon or rectum
• No active brain metastases or leptomeningeal metastases, except for patients who underwent definitive surgery or radiation without progression following repeat imaging (at least 4 weeks after the intervention) and were systemic steroids have been discontinued at least 2 weeks prior study treatment
• Known extended RAS and BRAF status, as per local standard of practice. Tumor mutation burden (TMB) and PD-L1 status will be collected when available but are not mandated for enrollment
• Patients must have progressed following exposure to all of the following agents in the advanced/metastatic setting OR in the neoadjuvant/adjuvant setting if disease recurred within 6 months of last treatment. Patients who were intolerant to prior systemic chemotherapy regimens are eligible if there is documented evidence of clinically significant intolerance despite adequate supportive measures
• Fluoropyrimidines (capecitabine or 5-FU)
• Irinotecan
• Oxaliplatin
• Anti-EGFR therapy if RAS and BRAF wild type with left colon primary

You may not qualify if:

• Prior allogeneic organ transplantation
• Prior immunotherapy with PD-1 or PD-L1 or CTLA-4 targeting agents
• Prior regorafenib
• Surgical intervention within 4 weeks prior to study treatment, except for minor procedures such as port placement
• Patients with a condition requiring systemic treatment with corticosteroids (\> 10 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
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of protocol therapy
• Strong CYP3A4 inducers or CYP3A4 inhibitors within 14 days prior to day 1 of protocol therapy
• Patients unwilling to refrain from drinking grapefruit juice and taking St. John's Wort while on study
• Herbal medications other than cannabidiol (CBD) unless reviewed by the principal investigator (PI) and deemed to unlikely interact with study drugs
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 12 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Patients must not have uncontrolled hypertension as defined by systolic blood pressure (SBP) \> 150mmHg or diastolic blood pressure (DBP) \> 90mmHg despite optimal medical management. Patients whose blood pressure can be controlled medically are allowed to be rescreened once blood pressure (BP) is under control
• Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs
• History of acute thrombotic venous events in the last 30 days before enrollment. If within 30 days, the patient should be on anticoagulants and without symptoms
• Obstructive bowel symptoms related to unresected primary or carcinomatosis

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms

Interventions

balstilimab; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; regorafenib

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Marwan G Fakih

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 28, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): January 28, 2027
• Study Completion (Estimated): January 28, 2027
• Last Updated: November 21, 2024

Record last verified: 2024-11