Study on Using PD-1 Blockade for Treating Locally Advanced Mismatch Repair Deficient Solid Tumors

Inclusion Criteria

• Must be willing and able to provide written consent to participate.
• Must be 18 years or older.
• Must have a good performance status, meaning fully active or restricted in physically strenuous activity but ambulatory.
• Must have a confirmed diagnosis of a locally advanced solid tumor.
• Tumors should typically be treated with therapy before surgery.
• No evidence of cancer spread to distant parts of the body.
• Must have a tumor that can be measured or evaluated by doctors.
• Tumor must show mismatch repair deficiency through specific tests.
• Women of childbearing potential must have a negative pregnancy test before starting treatment and agree to use effective birth control during the study and for 150 days after the last dose.
• Must have stable corticosteroid use if applicable.
• Must have a heart rhythm within normal limits.
• Must have adequate organ function based on blood tests, including:
  • Sufficient white blood cells, platelets, and hemoglobin levels.
  • Normal kidney and liver function.
  • Normal blood clotting times unless on stable anticoagulation therapy.

Exclusion Criteria

• Cancer that has spread or returned.
• Previous treatment with radiation, chemotherapy, or surgery for the tumor.
• For colorectal cancer patients, tumors causing bowel obstruction unless a temporary ostomy is in place.
• Other invasive cancers within the last 5 years, except for certain skin or cervical cancers.
• Immune system deficiencies or recent use of high-dose steroids or other immune-suppressing drugs.
• Active autoimmune diseases needing treatment in the past 2 years.
• Active infections needing treatment.
• Previous treatment with drugs targeting T-cell pathways.
• Severe immune-related side effects from past immunotherapy.
• Use of other cancer treatments or experimental therapies during the study.
• Known HIV or active Hepatitis B or C infections.
• Pregnant or breastfeeding women, or men planning to father children during the study and for 150 days after.
• Medical or psychiatric conditions that could interfere with participation.
• Recent live vaccinations.
• Recent major surgery or significant injury.
• History of lung disease.
• Allergies to TSR-042 or its components.