NAIO: Single Arm Study of Neoadjuvant Dostarlimab in Stage II and III Deficient Mismatch Repair Colon Cancers

Sponsor
University of Iowa (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05239546
Collaborator
(none)
29
1
72

Study Details

Study Description

Brief Summary

This is a Phase II, single arm study looking at the rate of major pathological response in Stage II and III colon cancer after 3 cycles of neoadjuvant Dostarlimab.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study aims to provide proof of principal that combined neoadjuvant immunotherapy (NAIO) with Dostarlimab alone has significant anti-tumor effect in deficient mismatch repair colon cancer (dMMR CC) with intact primary tumor.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
29 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II, Single Arm Study of Neoadjuvant Dostarlimab (TSR-042) in Stage II and III Deficient Mismatch Repair Colon Cancers
Anticipated Study Start Date :
Jun 1, 2023
Anticipated Primary Completion Date :
Jun 1, 2028
Anticipated Study Completion Date :
Jun 1, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Neoadjuvant Dostarlimab

Participants will receive Dostarlimab 500 mg IV every 3 weeks for 3 doses pre-operatively

Drug: Dostarlimab
Neoadjuvant Dostarlimab (500mg IV every 3 weeks x 3 doses prior to surgical resection) in patients with Stage II and III dMMR CC.
Other Names:
  • TSR-042
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage change in viable tumor cells (VTC) [After 3 cycles (up to 9 weeks)]

      To determine rate of Major Pathological Response (MPR) of <10% viable tumor cells (VTC) in Stage II and III Colon resected tumor after 3 cycles of neoadjuvant Dostarlimab, as measured by percent change pre- and post-treatment

    Secondary Outcome Measures

    1. Determine metastatic disease rate (MDR) [Up to 13 weeks]

      To determine rate of development of metastatic colon cancer on neoadjuvant Dostarlimab. MDR is defined as the proportion of patients who develop metastatic disease prior to surgery.

    2. Determine disease free survival (DFS) [Up to 3 years]

      DFS is defined as the time from treatment initiation to the date of first documentation of disease recurrence or death due to any cause.

    3. Determine overall response rate (ORR) [Up to 5 years]

      To estimate ORR on neoadjuvant Dostarlimab. ORR is defined as the proportion of patients with RECIST disease response (CR, PR). All patients that do not meet the criteria for an objective response by the analysis cutoff date will be considered non-responders.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Capable of understanding and complying with the protocol requirements and have signed the informed consent document.

    2. 18 years or older in age

    3. Biopsy proven Stage II or III dMMR (by IHC) Colon Cancer patients amendable to en block surgical resection as determined by colorectal surgeon.

    4. Biopsy specimen should be adequate for CD3+ and CD8+ immunostaining by HalioDx (See lab manual for specimen requirements).

    5. Potentially surgically resectable Stage II or III patients who are willing to try short duration of immunotherapy prior to surgery

    6. ECOG performance status < 1

    7. Absence of metastatic disease on CT CAP with Contrast within 28 days from treatment start

    8. Absolute neutrophil count ≥ 1,500/μL

    9. Platelets ≥ 100,000/μL

    10. Hemoglobin ≥ 9 g/dL

    11. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 60mL/min using the Cockcroft-Gault equation

    12. Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN

    13. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN

    14. International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy if PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants

    15. Participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to taking study treatment and agree to use an adequate method of contraception from screening through 180 days after the last dose of study treatment.

    Information must be captured appropriately within the site's source documents. Note:

    Abstinence is acceptable if this is the established and preferred contraception for the patient.

    1. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner starting with first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
    Exclusion Criteria:
    1. Known hypersensitivity to Dostarlimab components or excipients.

    2. Major surgery ≤ 3 weeks prior to initiating protocol therapy

    3. Received investigational therapy ≤ 3 months, or within a time interval less than at least 5 half- lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.

    4. History of radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.

    5. Heavy bleeding from the colon cancer tumors requiring PRBC transfusions that would require palliative surgical resection

    6. Received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy

    7. Symptomatic, partially obstructing tumors (patients with diverting ostomies are allowed)

    8. Concurrent, clinically significant, active malignancies within two years of study enrollment.

    9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

    10. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

    11. Diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.

    12. History of ≥ Grade 3 immune-related AE with prior immunotherapy, except for non-clinically significant lab abnormalities.

    13. Known uncontrolled Human immunodeficiency virus (HIV). Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with documented undetectable viral load and CD 4 count ≥350 within 6 months of the first dose of study treatment are eligible for this trial.

    14. Organ transplant recipients on immunosuppressive medications

    15. Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected).

    16. Prior history of interstitial lung disease.

    17. Received a live vaccine within 14 days of initiating protocol therapy.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • University of Iowa

    Investigators

    • Principal Investigator: Saima M Sharif, MD, University of Iowa Holden Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Saima Sharif, Clinical Associate Professor, University of Iowa
    ClinicalTrials.gov Identifier:
    NCT05239546
    Other Study ID Numbers:
    • 202105539
    First Posted:
    Feb 15, 2022
    Last Update Posted:
    Feb 15, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Saima Sharif, Clinical Associate Professor, University of Iowa
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 15, 2022