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Rectal AdenocarcinomaPhase 2NCT06780787

FOLFOX, Botensilimab, and Balstilimab for the Treatment of Localized Rectal Cancer Before Surgery

A Phase 2 study testing Balstilimab, Biospecimen Collection and Botensilimab in people with Rectal Adenocarcinoma and Stage IIA Rectal Cancer AJCC v8, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II trial tests how well fluorouracil, oxaliplatin and leucovorin calcium (folinic acid) (FOLFOX) with botensilimab and balstilimab given before surgery (neoadjuvant) works in treating patients with rectal adenocarcinoma that has not spread to other parts of the body (localized). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Balstilimab, Biospecimen Collection and Botensilimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
20 May 2025to 5 Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 and/or legally authorized representative
  • Assent, when appropriate, will be obtained per institutional guidelines
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Age: ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) ≤ 1
Show all 23Show fewer
  • Histologically confirmed adenocarcinoma of the rectum
  • Rectal involvement defined as involvement of the rectum within 12 cm proximal from anal verge
  • Radial margin of at least 3mm from the mesorectal fascia, with no threatened circumferential tumor margin based on MRI. No more than 4 lymph nodes (LN) with short axis > 1 cm
  • T3N0, or TxN1 or TxN2 clinical stage based on MRI staging
  • No evidence of distant metastatic disease based on imaging studies including CT chest and CT or MRI of abdomen and pelvis
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • Without bone marrow involvement: Platelets ≥ 100,000/mm^3
  • Hemoglobin ≥ 9g/dL
  • NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)
  • Aspartate aminotransferase (AST) ≤ 3.0 x ULN
  • Alanine aminotransferase (ALT) ≤ 3.0 x ULN
  • Creatinine < 1.5 x ULN or clearance of ≥ 40 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  • 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 9 months for women, and at least 6 months for men, after the last dose of oxaliplatin therapy. If patients discontinue oxaliplatin more than 9 months (females) or 6 months (males) before discontinuation of balstilimab and/or botensilimab, females and males of childbearing potential must use an effective method of birth control or abstain from sexual activity for the course of the study through at least 120 days after the last dose of balstilimab and/or botensilimab
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Who cannot join

  • Any treatment for rectal cancer prior to enrollment that includes (but not limited to) chemotherapy, radiation, and/or biological therapy
  • Any prior immunotherapy
  • Patients with a condition requiring systemic treatment with either 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
  • Prior allogeneic organ transplantation
  • Surgical intervention within 4 weeks prior to study treatment, except for minor procedures such as port placement or biopsies
  • Concurrent malignancy other than the diagnosis of rectal cancer, with the exception of curatively resected non-melanoma skin cancer, cervical cancer in situ, prostate cancer Gleason 6 or below that is localized to the prostate, or any other curatively resected cancer from which the patient remains in remission for at least 2 years without treatment
Show all 26Show fewer
  • Unstable cardiac disease as defined by one of the following:
  • Cardiac events such as myocardial infarction (MI) within the past 6 months
  • NYHA (New York Heart Association) heart failure class III-IV
  • Uncontrolled atrial fibrillation
  • Clinically significant uncontrolled illness
  • Females only: Pregnant or breastfeeding
  • Prior allergic reaction or hypersensitivity to any of the study drug components
  • 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 (excluding hypothyroidism, vitiligo, and psoriasis that is controlled with topical management)
  • 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
  • Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • History or current evidence of any condition, co-morbidity, therapy, any active infections (requiring antibiotics), 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
  • Grade 2 or above neuropathy at the time of enrollment
  • Dependence on total parenteral nutrition or intravenous hydration
  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Marwan Fakih, 626-256-4673 ext. 8308, mfakih@coh.org

    Marwan Fakih

    Recruiting

Other trials in United States

About this study

Official title: Phase II Clinical Trial of FOLFOX, Botensilimab, Plus Balstilimab in Patients With Localized Rectal Cancer

This phase II trial tests how well fluorouracil, oxaliplatin and leucovorin calcium (folinic acid) (FOLFOX) with botensilimab and balstilimab given before surgery (neoadjuvant) works in treating patients with rectal adenocarcinoma that has not spread to other parts of the body (localized). Currently, neoadjuvant therapy for rectal cancer includes chemotherapy and chemoradiation. Despite these aggressive treatments, only about half of patients achieve a complete clinical response. In fact, over half of rectal cancer patients go on to have surgery and often suffer post-surgery complications involving urine and bowel problems. Thus, there has been an increased focus on non-surgical treatments. Chemotherapy drugs, such as fluorouracil, oxaliplatin and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant FOLFOX with botensilimab and balstilimab may improve the rate of complete response and decrease the need for surgery and radiation therapy in patients with localized rectal adenocarcinoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the complete clinical response rate for patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

SECONDARY OBJECTIVES:

  1. To evaluate the safety of FOLFOX-BB in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

II. To estimate 3 year disease free survival rates in patients treated with FOLFOX-BB.

III. To estimate 3 year pelvic recurrence rates in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

IV. To estimate the duration of response in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

  1. To evaluate 5 year survival rates in patients in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).

EXPLORATORY OBJECTIVES:

  1. To examine changes in tumor microenvironment in response to FOLFOX-BB. II. To assess serial blood biomarkers to identify potential correlations with treatment response and outcomes.

OUTLINE:

Patients receive leucovorin calcium intravenously (IV) over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV over 46 hours on day 1 of each cycle. Patients also receive botensilimab IV over 60 minutes on day 1 of cycles 1 and 4 and balstilimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete clinical response may continue to receive balstilimab alone for an additional 12 cycles. Patients without complete clinical response may receive radiation therapy once daily (QD) on weekdays and capecitabine orally (PO) twice daily (BID) concurrently on days of radiation therapy per standard of care. Additionally, patients undergo blood sample collection, biopsy with endoscopy examination (exam), sigmoidoscopy, digital rectal exam, computed tomography (CT) and magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patient are followed at 30 and 90 days, then every 3 months within 1 year of start of treatment, followed by every 6 months for up to 2 years.

Being tested
Balstilimab, Biospecimen Collection, Botensilimab, Capecitabine, Computed Tomography
Medical subject headings
Rectal 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

  • 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

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • Computed TomographyProcedure or surgery

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

    Undergo CT

  • Digital Rectal ExaminationProcedure or surgery

    Also called DRE

    Undergo digital rectal exam

  • Endoscopic BiopsyProcedure or surgery

    Also called Endoscopy and Biopsy

    Undergo biopsy with endoscopic exam

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

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

    Undergo MRI

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate

    Undergo radiation therapy

  • SigmoidoscopyProcedure or surgery

    Also called Proctosigmoidoscopy

    Undergo sigmoidoscopy

Study groups in NCT06780787
Study groupRoleWhat they receive
Treatment (FOLFOX, botensilimab, balstilimab)ExperimentalPatients receive leucovorin calcium IV over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV over 46 hours on day 1 of each cycle. Patients also receive botensilimab IV over 60 minutes on day 1 of cycles 1 and 4 and balstilimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete clinical response may continue to receive balstilimab alone for an additional 12 cycles. Patients without complete clinical response may receive radiation therapy QD on weekdays and capecitabine PO BID concurrently on days of radiation therapy per standard of care. Additionally, patients undergo blood sample collection, biopsy with endoscopy exam, sigmoidoscopy, digital rectal exam, CT and MRI throughout the study.
Receives: Biological: Balstilimab; Procedure: Biospecimen Collection; Biological: Botensilimab; Drug: Capecitabine; Procedure: Computed Tomography; Procedure: Digital Rectal Examination; Procedure: Endoscopic Biopsy; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Radiation: Radiation Therapy; Procedure: Sigmoidoscopy

What is being measured

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

  1. Complete clinical response (cCR) rate

    Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. Univariate logistic regression was used to estimate odds ratios (OR) and 90% confidence interval (CI) for cCR

    Measured: At 3 months after treatment

Secondary outcomes (7)

  1. Overall response rate (ORR)

    ORR is calculated as the number of patients with complete response (per Response Evaluation Criteria in Solid Tumors version [v] 1.1) divided by the total number of treated/evaluable subjects. Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. Univariate logistic regression was used to estimate OR and 90% CI. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% CI.

    Measured: Up to 5 years

  2. Incidence of adverse events (AE) and serious adverse events (SAE)

    AE and SAE will be described and graded at all dose levels using Common Terminology Criteria in Adverse Events v 5.0. Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables.

    Measured: Up to 90 days post-treatment

  3. Disease free survival (DFS)

    Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. Univariate logistic regression was used to estimate OR and 90% CI. Cox proportional hazards models were used to estimate HR with 95% CI. DFS distributions will be estimated using the Kaplan-Meier method.

    Measured: From the date of study enrollment until the recurrence of disease or death, whichever occurs first, assessed at 3 years post-treatment

  4. Progression-free survival (PFS)

    Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. PFS distributions will be estimated using the Kaplan-Meier method. Kaplan-Meier method was used to plot PFS curves, and the log-rank test was applied to compare the distribution between groups. Cox proportional hazards models were used to estimate HR with 95% CI.

    Measured: From the date of study enrollment until objective tumor progression or death, assessed up to 5 years

  5. Pelvic recurrence rate

    Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables.

    Measured: At 3 years after treatment

  6. Duration of response (DOR)

    Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. DOR distributions will be estimated using the Kaplan-Meier method.

    Measured: From treatment response to progression or death, assessed up to 3 years

  7. Overall survival (OS)

    Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. OS distributions will be estimated using the Kaplan-Meier method. Kaplan-Meier method was used to plot OS curves, and the log-rank test was applied to compare the distribution between groups. Cox proportional hazards models were used to estimate HR with 95% CI.

    Measured: From the date of study enrollment to the date of death, assessed up to 5 years post-treatment

Timeline

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

  1. First posted17 Jan 2025
  2. Study start20 May 2025
  3. Primary completion5 Nov 2027 (estimated)
  4. Study completion5 Nov 2027 (estimated)

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06780787
Sponsor's protocol ID
24589
Other IDs
NCI-2025-00072, 24589, P30CA033572
Status last verified
Jun 2026
First submitted
13 Jan 2025
Last updated
29 Jun 2026
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, Biospecimen Collection and Botensilimab in people with Rectal Adenocarcinoma and Stage IIA Rectal Cancer AJCC v8, run by City of Hope Medical Center at 1 site in United States.

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 23 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

This study is still under way. Results are not available in the source record yet.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete clinical response (cCR) rate (time frame: At 3 months after treatment). 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 NCT06780787.

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 29 Jun 2026.

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