Combination Immunotherapy in Colorectal Cancer

Browse trials for

• Colorectal Neoplasms 5,599
• Diabetes Mellitus, Insulin-Dependent, 12 32

Keywords

• Immunotherapy
• Colorectal Cancer
• PD-1
• CTLA-4

Colorectal Neoplasms

5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.

This study's enrollment of 26 is below the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.

Lead sponsor

Weill Medical College of Cornell University is the lead sponsor of 867 studies on the registry; 160 are open to participants now.

Of its 119 completed or terminated interventional studies of FDA-regulated products, 91 (76%) have results posted.

Study arms

• Experimental
  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.

  Drug: Botensilimab · Drug: Balstilimab

• Experimental
  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.

  Drug: Botensilimab · Drug: Balstilimab

• Experimental
  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.

  Drug: Botensilimab · Drug: Balstilimab

Interventions

• DrugBotensilimab

  Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description.

• DrugBalstilimab

  Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.

Primary outcomes

1. Cohort A and B: Pathological Overall Response (pOR) Rate Determined by Analysis of Tissue Resected During Surgery Reported by Cohort

   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.

   Time frame: Immediately following surgical resection of the primary tumor

2. 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

   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.

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

3. 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)

   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.

   Time frame: 12 weeks after treatment initiation date (Day 0)

4. Cohort C: Composite Rate of Clinical Complete Response or Major Pathological Response at 6 Months

   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.

   Time frame: 6 months

Secondary outcomes

1. All Cohorts: Changes in Minimal Residual Disease Assessed Using ctDNA Pre- and 30 Days Post-surgical Resection

   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.

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

2. All Cohorts: Changes in Minimal Residual Disease Assessed Using ctDNA Pre- and 30 Days Post-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.

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

Baseline characteristics

Study documents

• Protocol and statistical analysis plan · Mar 10, 2026

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No