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

• Status: Not yet recruiting
• Trial end date: 2029-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Iowa

Criteria

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.

16. 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.