Trial Outcomes & Findings for Combination Immunotherapy in Colorectal Cancer (NCT NCT05571293)

Last Updated: 2026-05-22

Results Overview

Resected tumors will be examined in their entirety, and regression of resected tumors was assessed by estimating the percentage of residual viable tumor of the macroscopically identifiable tumor bed, as identified on routine hematoxylin and eosin (H\&E) staining. In addition, regression will be classified using the Mandard tumor regression grading system. Major pathologic response (MPR) will be defined as ≤10% of residual viable tumor cells (or ≥ 90% response), corresponding to Mandard tumor regression grade 1 (CR) or 2 (near-CR). PR will be defined as at least 50% tumor regression. However, considering the lack of consensus on the definition of PR after immunotherapy, tumors with \>50% and \<90% residual viable tumor will be labeled accordingly as '10-50% tumor regression', as per the NICHE study (Chalabi et. al., 2020). When analyzing pMMR responders versus pMMR nonresponders, this subgroup will be included in the group of nonresponders.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Immediately following surgical resection of the primary tumor

Results posted on

2026-05-22

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Overall Study STARTED	12	13	1
Overall Study COMPLETED	10	12	1
Overall Study NOT COMPLETED	2	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Overall Study Subject determined to be ineligible due to incomplete tumor resection.	1	0
Overall Study Subject determined to be ineligible after enrollment due to identification of metastatic disease.	1	0
Overall Study Subject has pending visit	0	1

Baseline Characteristics

Combination Immunotherapy in Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=10 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: n=13 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: n=1 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=6 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=2 Participants	5 Participants n=4 Participants	0 Participants n=6 Participants	12 Participants n=8 Participants
Age, Categorical >=65 years	3 Participants n=2 Participants	8 Participants n=4 Participants	1 Participants n=6 Participants	12 Participants n=8 Participants
Sex: Female, Male Female	5 Participants n=2 Participants	6 Participants n=4 Participants	0 Participants n=6 Participants	11 Participants n=8 Participants
Sex: Female, Male Male	5 Participants n=2 Participants	7 Participants n=4 Participants	1 Participants n=6 Participants	13 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=6 Participants	1 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=2 Participants	11 Participants n=4 Participants	1 Participants n=6 Participants	21 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=2 Participants	2 Participants n=4 Participants	0 Participants n=6 Participants	2 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=6 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	1 Participants n=2 Participants	3 Participants n=4 Participants	0 Participants n=6 Participants	4 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=6 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	2 Participants n=2 Participants	2 Participants n=4 Participants	0 Participants n=6 Participants	4 Participants n=8 Participants
Race (NIH/OMB) White	5 Participants n=2 Participants	6 Participants n=4 Participants	1 Participants n=6 Participants	12 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=2 Participants	0 Participants n=4 Participants	0 Participants n=6 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=2 Participants	2 Participants n=4 Participants	0 Participants n=6 Participants	4 Participants n=8 Participants
Colon Cancer Type: dMMR	3 Participants n=2 Participants	0 Participants n=4 Participants	1 Participants n=6 Participants	4 Participants n=8 Participants
Colon Cancer Type: pMMR	7 Participants n=2 Participants	13 Participants n=4 Participants	0 Participants n=6 Participants	20 Participants n=8 Participants
pMMR	7 Participants n=2 Participants	13 Participants n=4 Participants	0 Participants n=6 Participants	20 Participants n=8 Participants

PRIMARY outcome

Timeframe: Immediately following surgical resection of the primary tumor

Population: The analysis population includes all eligible enrolled patients who met protocol-defined criteria and were evaluable for the primary outcome. Two enrolled subjects were excluded from the primary analysis: one subject was determined to be ineligible due to incomplete tumor resection, and one subject was determined to be ineligible after enrollment following identification of metastatic disease. Patients from cohort C were not included in the analysis of this outcome measure per study protocol.

Outcome measures

Outcome measures
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=10 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: n=13 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Cohort A and B: Pathological Overall Response (pOR) Rate Determined by Analysis of Tissue Resected During Surgery Reported by Cohort	7 Participants	8 Participants	—

PRIMARY outcome

Timeframe: From date of last dose of study drug up to 90 days after

Population: The analysis population includes all eligible enrolled patients who met protocol-defined criteria and were evaluable for the primary outcome. Two enrolled subjects were excluded from the primary analysis: one subject was determined to be ineligible due to incomplete tumor resection, and one subject was determined to be ineligible after enrollment following identification of metastatic disease. Cohorts B and C were not included in the data analysis for this primary outcome per protocol.

Safety will be assessed by evaluation of the number of participants experiencing SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 days post-the last dose of study drug. Grade 3 or 4 adverse event possibly, probably or definitely attributed to bot/bal. Patients from cohorts B and C were not included in the analysis of this outcome measure per study protocol.

Outcome measures

Outcome measures
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=10 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Cohort A: Number of Participants Who Experience Potentially Treatment-related SAEs According to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 Days Following the Last Treatment With Balstilimab or Botensilimab	2 Participants	—	—

PRIMARY outcome

Timeframe: 12 weeks after treatment initiation date (Day 0)

Population: This is not appliable for cohorts B and C per the specified study reporting. The analysis population includes all eligible enrolled patients who met protocol-defined criteria and were evaluable for the primary outcome. Two enrolled subjects were excluded from the primary analysis: one subject was determined to be ineligible due to incomplete tumor resection, and one subject was determined to be ineligible after enrollment following identification of metastatic disease.

Any AEs or SAEs that lead to a delay in surgery greater than 12 weeks from treatment initiation (Day 0) will be recorded. If there are ≥ 2 patients out of the first 6 patients, or ≥ 4 patients out of the full 12 participants (≥33%), with AEs/SAEs that lead to a delay in surgery beyond 12 weeks from treatment initiation, with the exception of COVID-related procedural delays, then this combination of botensilimab and balstilimab, at these dosages will not be considered feasible in this population.

Outcome measures

Outcome measures
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=10 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Cohort A: Number of Participants Who Experience Treatment-related Complications Leading to Delays of 12 Weeks or More in Surgery After Treatment Initiation (Day 0)	0 Participants	—	—

PRIMARY outcome

Timeframe: 6 months

Population: This outcome measure is not applicable to cohorts A and B per the study protocol.

The joint patient-surgeon decision to defer surgery for a watch and wait (Watch-\&-Wait W\&W) approach is allowed as long as the patient is demonstrating sustained response as determined by clinical, radiographic, endoscopic, and/or blood-based biomarkers. For participants who elect to undergo surgery, pathological response will be determined as described above. The key endpoint here will be "Major pathological response (MPR; CR + near-CR). Patients who opt for non-operative management based on clinical response will be considered to have CR. Complete response will be determined by the treating physician and surgeon based on composite subjective and objective assessments of clinical, radiographic, endoscopic, blood-based biomarker assessments, and/or the absence of clinical and radiographic progression.

Outcome measures

Outcome measures
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=1 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Cohort C: Composite Rate of Clinical Complete Response or Major Pathological Response at 6 Months	100 percentage of patients	—	—

SECONDARY outcome

Timeframe: Immediately prior to initiation of therapy and 30 days following surgical resection

Population: The analysis population includes patients who had ctDNA collected at baseline prior to initiation of therapy. Per protocol, ctDNA collection was optional. Patients without baseline ctDNA collection were not included in this analysis.

Summary statistics including mean, standard deviation will be provided for ctDNA levels obtained at various time points. Linear mixed-effects models will be used to model longitudinal biomarker values. Simultaneous testing of general linear hypotheses will be used to evaluate contrasts of interest.

Outcome measures

Outcome measures
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=2 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: n=6 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: n=1 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
All Cohorts: Changes in Minimal Residual Disease Assessed Using ctDNA Pre- and 30 Days Post-surgical Resection Baseline	0.42 MTM/ml Standard Deviation 0.355	15.77 MTM/ml Standard Deviation 4.35	5.7 MTM/ml Standard Deviation NA Only 1 participant in this cohort so standard deviation is not applicable.
All Cohorts: Changes in Minimal Residual Disease Assessed Using ctDNA Pre- and 30 Days Post-surgical Resection 30 Days Post Resection	0.00 MTM/ml Standard Deviation 0.00	0.00 MTM/ml Standard Deviation 0.00	0.00 MTM/ml Standard Deviation 0.00

SECONDARY outcome

Timeframe: Immediately prior to initiation of therapy and 30 days following surgical resection

Median and range will be provided for ctDNA levels obtained at various time points. Linear mixed-effects models will be used to model longitudinal biomarker values. Simultaneous testing of general linear hypotheses will be used to evaluate contrasts of interest.

Outcome measures

Outcome measures
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=2 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: n=6 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: n=1 Participants Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
All Cohorts: Changes in Minimal Residual Disease Assessed Using ctDNA Pre- and 30 Days Post-surgical Resection 30 Days Post Resection	0.00 MTM/ml Interval 0.0 to 0.0	0.00 MTM/ml Interval 0.0 to 0.0	0.00 MTM/ml Interval 0.0 to 0.0
All Cohorts: Changes in Minimal Residual Disease Assessed Using ctDNA Pre- and 30 Days Post-surgical Resection Baseline	0.42 MTM/ml Interval 0.06 to 0.77	4.35 MTM/ml Interval 0.05 to 4.35	5.7 MTM/ml Interval 5.7 to 5.7

Adverse Events

Cohort A: Botensilimab and Balstilimab (Bot/Bal)

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort B:

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Cohort C:

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=12 participants at risk Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: n=13 participants at risk Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: n=1 participants at risk Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Gastrointestinal disorders Diarrhea	16.7% 2/12 • Number of events 2 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Number of events 1 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Cardiac disorders Atrial Fibrillation	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Number of events 1 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Colitis	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Number of events 2 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Number of events 1 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
General disorders Edema in Limbs	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Number of events 1 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
General disorders Fatigue	8.3% 1/12 • Number of events 1 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Number of events 1 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Vascular disorders Hypertension	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Number of events 1 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.

Other adverse events

Additional Information

Casey Owens

Weill Cornell Medicine

Phone: 6469626200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort A: Botensilimab and Balstilimab (Bot/Bal) n=12 participants at risk Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort B: n=13 participants at risk Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.	Cohort C: n=1 participants at risk Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer. Botensilimab: Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description. Balstilimab: Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Nervous system disorders Dysgeusia	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
General disorders Edema in limbs	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	30.8% 4/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
General disorders Fatigue	25.0% 3/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	61.5% 8/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
General disorders Pyrexia	33.3% 4/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	46.2% 6/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Vascular disorders Hypertension	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	23.1% 3/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Nausea	33.3% 4/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	23.1% 3/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
General disorders Pain	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Infections and infestations Skin Infection	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	100.0% 1/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	23.1% 3/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Infections and infestations Urinary Tract Infection	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	7.7% 1/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Abdominal Pain	8.3% 1/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	23.1% 3/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
General disorders Chills	25.0% 3/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Diarrhea	33.3% 4/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	46.2% 6/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Nervous system disorders Dizziness	16.7% 2/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Nervous system disorders Headache	33.3% 4/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	15.4% 2/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Vomitting	33.3% 4/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Colitis	8.3% 1/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	23.1% 3/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Constipation	16.7% 2/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	100.0% 1/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Gastrointestinal disorders Abdominal Distension	0.00% 0/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	100.0% 1/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Blood and lymphatic system disorders Anemia	8.3% 1/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	15.4% 2/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.
Metabolism and nutrition disorders Anorexia	8.3% 1/12 • Adverse events following initiation of therapy up to 90 days from last treatment.	15.4% 2/13 • Adverse events following initiation of therapy up to 90 days from last treatment.	0.00% 0/1 • Adverse events following initiation of therapy up to 90 days from last treatment.