Back to resultsCombination Immunotherapy in Colorectal Cancer (NEST-1)
Primary Purpose
Colorectal Neoplasms
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Botensilimab
Balstilimab
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms focused on measuring Immunotherapy, Colorectal Cancer, PD-1, CTLA-4
Eligibility Criteria
Inclusion Criteria:
- 18 years of age or older
- Stage 1-3 adenocarcinoma of the colon with plans to have a surgical resection
- If capable of becoming pregnant, or getting someone else pregnant, must be willing to use highly effective contraception from Screening period through 90 days following the last dose of study drug
Exclusion Criteria:
- Metastatic cancer (cancer that has spread to other parts of the body)
- Previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1
- Currently participating in another study and receiving a study drug
- History of severe allergic reactions to immunotherapies
- Pregnant or breastfeeding
- Active infection requiring treatment
- On immunosuppressive medications
- Active cardiovascular disease, such as stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure, or serious uncontrolled cardiac arrhythmia requiring medication that may prevent surgery
Sites / Locations
- Weill Cornell Medicine/NewYork-Presbyterian HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Botensilimab and balstilimab (bot/bal)
Arm Description
Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. A single dose of botensilimab (75 mg IV), and two doses of balstilimab (240 mg IV), will be administered on the same day. A second dose of balstilimab (240 mg IV) will be administered 14 days later (-2 +5 days). Surgical resection will occur 1-6 weeks following the second dose of balstilimab.
Outcomes
Primary Outcome Measures
Pathological overall response (pOR) rate determined by analysis of tissue resected during surgery
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.
Number of Adverse Events
Safety will be assessed by evaluation of the number of AEs according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 days post-the last dose of study drug
Number of Serious Adverse Events
Safety will be assessed by evaluation of the number of SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 days post-the last dose of study drug
Number of complications leading to delays of 12 weeks or more in surgery after initiation of treatment
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.
Secondary Outcome Measures
Changes in Minimal Residual Disease assessed using ctDNA pre- and post-surgical resection
Summary statistics including mean, standard deviation, 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.
Full Information
NCT ID
NCT05571293
First Posted
October 4, 2022
Last Updated
March 21, 2023
Sponsor
Weill Medical College of Cornell University
Collaborators
Agenus Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05571293
Brief Title
Combination Immunotherapy in Colorectal Cancer
Acronym
NEST-1
Official Title
Novel Exploratory Study to Test Combination of Botensilimab and Balstilimab Immunotherapy in Resectable Colorectal Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 17, 2023 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
Agenus Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a pilot study to see whether a combination of two investigational drugs that target the immune system can be given to people with colorectal cancer before surgically removing the tumor. This study is also being done to see what side effects this combination of drugs has and what effect they have on colorectal cancer. The two monoclonal antibodies are balstilimab, a programmed cell death protein 1 (PD-1) inhibitor, and botensilimab, a cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor. Participants will receive a dose of balstilimab and botensilimab, both given intravenously (IV), followed by a second dose of balstilimab approximately 2 weeks after the first dose. Both doses of balstilimab and the single dose of botensilimab will be given during an 8 weeks period before surgery.
Detailed Description
This is a pilot study to assess the feasibility, safety, and efficacy of using a combination of a programmed cell death protein 1 (PD-1) inhibitor (balstilimab) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitor (botensilimab) in the neoadjuvant setting in patients with colorectal cancer, prior to resection. This is a single-center, single-arm, open-label, pilot study in which patients will receive 2 doses of intravenous (IV) balstilimab (each dose approximately 2 weeks apart), and a single dose of botensilimab IV, within 8 weeks prior to resection in patients with colon cancer. Following surgical resection, participants will return to the clinic for 2 follow-up visits. Follow-up visit 1 will occur 1-3 weeks post-op (+/- 7 days), and follow-up visit 2 (+/- 7 days) will occur 4-6 weeks post-op.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms
Keywords
Immunotherapy, Colorectal Cancer, PD-1, CTLA-4
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Botensilimab and balstilimab (bot/bal)
Arm Type
Experimental
Arm Description
Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. A single dose of botensilimab (75 mg IV), and two doses of balstilimab (240 mg IV), will be administered on the same day. A second dose of balstilimab (240 mg IV) will be administered 14 days later (-2 +5 days). Surgical resection will occur 1-6 weeks following the second dose of balstilimab.
Intervention Type
Drug
Intervention Name(s)
Botensilimab
Intervention Description
Botensilimab, a CTLA-4 inhibitor, will be administered prior to surgical resection as described in the arm description.
Intervention Type
Drug
Intervention Name(s)
Balstilimab
Intervention Description
Balstilimab, a PD-1 inhibitor, will be administered prior to surgical resection as described in the arm description.
Primary Outcome Measure Information:
Title
Pathological overall response (pOR) rate determined by analysis of tissue resected during surgery
Description
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
Day 30
Title
Number of Adverse Events
Description
Safety will be assessed by evaluation of the number of AEs according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 days post-the last dose of study drug
Time Frame
Day 105
Title
Number of Serious Adverse Events
Description
Safety will be assessed by evaluation of the number of SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at 90 days post-the last dose of study drug
Time Frame
Day 105
Title
Number of complications leading to delays of 12 weeks or more in surgery after initiation of treatment
Description
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
Day 90
Secondary Outcome Measure Information:
Title
Changes in Minimal Residual Disease assessed using ctDNA pre- and post-surgical resection
Description
Summary statistics including mean, standard deviation, 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
Baseline, Day 0, Day 14, Day 45, Day 60
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years of age or older
Stage 1-3 adenocarcinoma of the colon with plans to have a surgical resection
If capable of becoming pregnant, or getting someone else pregnant, must be willing to use highly effective contraception from Screening period through 90 days following the last dose of study drug
Exclusion Criteria:
Metastatic cancer (cancer that has spread to other parts of the body)
Previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1
Currently participating in another study and receiving a study drug
History of severe allergic reactions to immunotherapies
Pregnant or breastfeeding
Active infection requiring treatment
On immunosuppressive medications
Active cardiovascular disease, such as stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure, or serious uncontrolled cardiac arrhythmia requiring medication that may prevent surgery
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Casey Owens
Phone
646-962-8189
Email
cdo4001@med.cornell.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Myriam Elizaire-Williams
Phone
646-962-4807
Email
mye4001@med.cornell.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pashtoon Kasi, M.D.
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medicine/NewYork-Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Casey Owens
Phone
646-962-8189
Email
cdo4001@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Myriam Elizaire-Williams
Phone
646-962-4807
Email
mye4001@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Pashtoon Kasi, M.D.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Combination Immunotherapy in Colorectal Cancer
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