This phase II trial tests how well giving botensilimab and balstilimab prior or to surgery (neoadjuvent) works for the treatment of colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that can be removed by surgery (resectable) colorectal cancer. 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. Giving botensilimab and balstilimab before surgery may make the tumor smaller. Giving neoadjuvant botensilimab and balstilimab may be effective for the treatment of advanced resectable colorectal cancer.
PRIMARY OBJECTIVE: I. To estimate the two-year disease-free survival (DFS) rate when treating advanced mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer with botensilimab (BOT)/balstilimab (BAL) followed by surgery. SECONDARY OBJECTIVES: I. To determine the major pathologic response rate for patients with advanced mismatch repair proficient or microsatellite stable (pMMR or MSS) colorectal cancer treated with botensilimab (BOT) + balstilimab (BAL) followed by surgery. II. To evaluate the safety of treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery. III. To estimate the pathologic response rate when treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery. IV. To estimate the three-year disease-free survival rate when treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery. V. To estimate the median recurrence free survival in patients with advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery, among patients who are disease free at the time of surgery. VI. To describe the proportion of patients that get all four doses of BAL. VII. To describe the quality of life of patients with advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery. VIII. To describe the time to surgery after treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery. IX. To describe the percent of pMMR/MSS colorectal cancer patients treated with BOT/BAL followed by surgery in which adjuvant therapy is recommended, amount and type received, as well as patient refusal rate. EXPLORATORY OBJECTIVES: I. To examine changes in tumor microenvironment in response to BOT/BAL when treating advanced pMMR/MSS colorectal cancer. II. To explore the serial changes in circulating tumor deoxyribonucleic acid (ctdna) when treating advanced pMMR/MSS colorectal cancer with BOT/BAL followed by surgery. III. To explore markers on baseline imaging that correlate with response and long-term outcomes. IV. To determine ctDNA and cell free deoxyribonucleic acid (cfDNA) detectability before, during and after neoadjuvant BOT/BAL and curative-intent surgical resection. V. To describe the association between detectable ctDNA and cfDNA measured before, during and after neoadjuvant post-neoadjuvant treatment and surgery with DFS and pathologic response. VI. To describe the difference in time between ctDNA and cfDNA detection (molecular recurrence) and radiographic evidence of disease recurrence following definitive treatment among patients who achieved undetectable ctDNA and/or cfDNA levels after surgery. VII. Among patients that get presurgical standard of care (SOC) imaging, to describe the presurgical radiologic response. OUTLINE: Patients receive botensilimab intravenously (IV), over 30 minutes, on day 1 and balstilimab IV, over 30 minutes, on days 1, 15, 29 and 43 in the absence of disease progression or unacceptable toxicity. 5-16 weeks later, patients then undergo standard of care resection surgery. Patients undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 2 weeks, 4 weeks and every 3 months for 2 years then every 6 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Given IV
Undergo blood sample collection
Given IV
Undergo CT scan
Undergo MRI
CTCA at Western Regional Medical Center
Goodyear, Arizona, United States
City of Hope Corona
Corona, California, United States
City of Hope Medical Center
Duarte, California, United States
City of Hope Seacliff
Huntington Beach, California, United States
City of Hope at Irvine Lennar
Irvine, California, United States
City of Hope at Long Beach Elm
Long Beach, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
City of Hope Upland
Upland, California, United States
City of Hope Atlanta Cancer Center
Newnan, Georgia, United States
City of Hope at Illinois Chicago Downtown
Chicago, Illinois, United States
...and 1 more locations
Two-year disease-free survival rate
Defined as the percentage of patients that remain free from any signs of colon cancer at two years post-enrollment. Will be compared to the historical control rate of 76.8% (from the FoXTROT adjuvant chemotherapy arm) using a one-sided, one-sample log-rank test.
Time frame: At 2 years post enrollment
Major pathologic response rate
Defined as the proportion of patients achieving major pathologic responses defined as either a \>= 90% tumor reduction or 100% reduction (near complete response + pathologic complete response). Will be compared with the historical control rate of 10% using a one-sided, continuity corrected Z-test.
Time frame: Up to 3 years
Incidence of adverse events
Assessed according to Common Terminology Criteria for Adverse Events version 6.0. Will be summarized using descriptive statistics.
Time frame: Up to 3 years
Pathologic response rate
Defined as the proportion of patients achieving a pathologic response, defined as a ≥ 50% tumor reduction.
Time frame: Up to 3 years
Three-year disease-free survival rate
Defined as the percentage of patients that remain free from any signs of colon cancer at three years post-enrollment. Will be summarized similar to 2-year survival but at the 3-year mark.
Time frame: At 3 years post-enrollment
Recurrence free survival
Assessed among patients that are disease free at the time of surgery. Will be graphically represented using Kaplan-Meier methods and summarized using descriptive statistics.
Time frame: Time from surgery to date of first cancer recurrence or death as a result of any cause, whichever occurs first, up to 3 years
Number of patients who get all four doses of balstilimab divided by number of enrolled patients
Will be summarized using descriptive statistics.
Time frame: Up to 3 months
Change in Eastern Cooperative Oncology Group
Will be summarized using descriptive statistics.
Time frame: Up to 3 years
Time to surgery
Will be summarized using descriptive statistics.
Time frame: Up to 9 months
Proportion of patients in which adjuvant therapy is recommended, of these the percent who refuse adjuvant therapy
Will be summarized using descriptive statistics.
Time frame: Up to 9 months
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