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Advanced Colon AdenocarcinomaPhase 2NCT06575725

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

A Phase 2 study testing Balstilimab, Biopsy and Biospecimen Collection in people with Advanced Colon Adenocarcinoma and Advanced Colorectal Adenocarcinoma, run by City of Hope Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Balstilimab, Biopsy and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 Nov 2024to 28 Jan 2027
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Patients must have evidence of progression on or after the last treatment received and within 6 months prior to study enrollment
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy, excluding endocrinopathies stable on medication, stable neuropathy that is grade 2 or less, and alopecia
  • Patients may not have metastatic liver disease defined as: No history of liver metastatic disease OR history of resected or ablated liver metastases without evidence of disease recurrence in the liver for at least 4 months before enrollment
  • Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 x ULN
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL/min (measured or calculated using the Cockroft-Gault formula)
  • Hemoglobin ≥ 9 g/dl
  • Absolute neutrophil count (ANC) ≥ 1,500/µl
  • Platelets ≥ 75,000/mm^3
  • Albumin ≥ 3.0 g/dl
  • Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 120 days after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men) OR have not been free from menses for > 1 year and ≥ 50 years of age (women only) OR amenorrheic for ≥ 2 years without a hysterectomy and bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation (women only) OR status is post-hysterectomy, bilateral oophorectomy, or tubal ligation (women only)

Who cannot join

  • 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
Show all 31Show fewer
  • 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
  • Inability to swallow and absorb oral tablets (such as but not limited to inability to swallow pills, malabsorption issues, ongoing nausea or vomiting)
  • Non-healing wounds
  • Symptomatic active bleeding
  • Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids
  • 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 patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
  • Known previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to cycle 1 day 1 (C1D1)
  • Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required
  • Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are receiving or who have received anti-HBV therapy and have undetectable HBV deoxyribonucleic acid (DNA) for at least 6 months prior to study entry are eligible. Serological testing for HBV at screening is not required
  • Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for HCV at screening is not required
  • Dependence on total parenteral nutrition or intravenous hydration
  • Clinically significant uncontrolled illness
  • Concurrent non-colorectal second malignancy (present during screening) requiring treatment or history of a non-colorectal second primary metastatic malignancy within 2 years prior to the first dose of study treatment. Patients 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. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial after PI approval
  • Females only: Pregnant or breastfeeding
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

About this study

Official title: A Phase 2 Study of Botensilimab, Balstilimab and Regorafenib in Patients With Microsatellite Stable Colorectal Cancer

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.

Read the detailed description

COPRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of botensilimab, balstilimab and regorafenib (BBR) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients without metastatic liver lesions in the safety run-in. (Safety lead-in) II. Compare the overall response rate in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients without metastatic liver lesions receiving botensilimab, balstilimab and regorafenib (BBR) versus botensilimab and balstilimab (BB), by treatment arm. (Phase II)

SECONDARY OBJECTIVES:

  1. Estimate the overall survival in MSS mCRC patients without metastatic liver lesions receiving BBR and BB, by treatment arm.

II. Estimate the progression free survival in MSS mCRC patients without metastatic liver lesions receiving BBR and BB, by treatment arm.

III. Estimate the duration of response (DOR) in MSS mCRC patients without metastatic liver lesions receiving BBR and BB that experience a response to therapy, by treatment arm.

IV. Describe the safety of giving to BBR and BB to patients with MSS mCRC without metastatic liver lesions, by treatment arm.

EXPLORATORY OBJECTIVE:

  1. Through the performance of baseline and on treatment biopsies and serial blood work (cytokines and flow cytometry), explore potential biomarkers of response to BBR and BB therapy given to MSS mCRC patients without metastatic liver lesions, by treatment arm.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM BBR: Patients receive botensilimab intravenously (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 orally (PO) once daily (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 computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection throughout the trial. Patients also undergo tumor biopsy during screening and on study.

ARM BB: 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.

After completion of study treatment, patients are followed up at 30 and 90 days and then every 2-3 months for 5 years.

Being tested
Balstilimab, Biopsy, Biospecimen Collection, Botensilimab, Computed Tomography
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BalstilimabBiological

    Also called AGEN 2034, AGEN-2034, AGEN2034

    Given IV

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • BotensilimabBiological

    Also called AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • RegorafenibDrug

    Also called BAY 73-4506 Monohydrate, BAY-73-4506 Monohydrate, Regorafenib Monohydrate, Stivarga

    Given PO

Study groups in NCT06575725
Study groupRoleWhat they receive
Arm BB (botensilimab, balstilimab)ExperimentalPatients 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.
Receives: Biological: Balstilimab; Procedure: Biopsy; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging
Arm BBR (botensilimab, balstilimab, regorafenib)ExperimentalPatients 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.
Receives: Biological: Balstilimab; Procedure: Biopsy; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose limiting toxicities (Safety lead in)

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

    Measured: During cycle 1 (42 days)

  2. Treatment related adverse event rates (Safety lead in)

    Assessed by NCI CTCAE version 5.0.

    Measured: During cycle 1 (42 days)

  3. 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.

    Measured: Up to 5 years after completion of study treatment

  4. 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.

    Measured: Up to 5 years after completion of study treatment

Secondary outcomes (4)

  1. Overall survival

    Will be estimated by the Kaplan-Meier method and calculated with 95% confidence intervals (CIs).

    Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals.

    Measured: 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

  2. Progression free survival

    Will be estimated by the Kaplan-Meier method and will be calculated with 95% CIs.

    Will be summarized by number, and percentage, along with Clopper-Pearson exact binomial confidence intervals.

    Measured: 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

  3. Duration of treatment response

    Defined as time to progression or death, starting at the time when a response is experienced.

    Measured: Up to 5 years after completion of study treatment

  4. Incidence of adverse events

    Defined as toxicity, graded according to the NCI CTCAE v5.0. Toxicity data will be summarized in frequency tables by category and grade to evaluate the safety profile of the combination therapy.

    Measured: Up to 90 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2024
  2. Study start1 Nov 2024 (estimated)
  3. Primary completion28 Jan 2027 (estimated)
  4. Study completion28 Jan 2027 (estimated)

Why it stopped: Abandoned 9/23/24

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06575725
Sponsor's protocol ID
24074
Other IDs
NCI-2024-06706, 24074, P30CA033572
Status last verified
Nov 2024
First submitted
23 Aug 2024
Last updated
21 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Balstilimab, Biopsy and Biospecimen Collection in people with Advanced Colon Adenocarcinoma and Advanced Colorectal Adenocarcinoma, run by City of Hope Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicities (Safety lead in) (time frame: During cycle 1 (42 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06575725.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2024.

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