The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial

Exclusion Criteria

• •1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• •2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• •3. Has a known history of active, untreated TB (Bacillus Tuberculosis)
• •4. Hypersensitivity to pembrolizumab or any of its excipients.
• •5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• •6. Has had prior chemotherapy within 28 days prior to study Day 1, or targeted small molecule therapy or radiation therapy within 14 days prior to study Day 1. Patients who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• •7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, and in situ cervical cancer that has undergone potentially curative therapy.
• •8. Has 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• •9. Has known history of, or any evidence of active, non-infectious pneumonitis.
• •10. Has an active infection requiring systemic therapy.
• •11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after last dose of cyclophosphamide or fludarabine or 120 days after the last dose of pembrolizumab.
• •14. Has a known history of Human Immunodeficiency Virus (HIV) (e.g. HIV 1/2 antibody positive) or Human T-Cell Lymphotropic Virus (HTLV).
• •15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• •16. Untreated syphilis.
• •17. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• •Subjects with ongoing prior use of systemic steroid therapy within 4 weeks before the TILs infusion will be excluded. Use of topical, intranasal and inhaled corticosteroids, or systemic corticosteroids at physiologic doses are allowed.
• •2. Initiation of pembrolizumab therapy must occur more than 21 days after the last dose of fludarabine.
• •3. Resolution of TIL protocol related adverse events to grade 2 or less. Otherwise, patients may proceed with pembrolizumab therapy if the treating investigator, after discussion with the Sponsor, determines that residual TIL therapy related adverse events are not clinically significant.
• •1. Has an active infection requiring systemic therapy. (Prophylactic antibiotics and antiviral agents are allowed.)
• •2. Has developed a condition or requires a therapy that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •3. Development of a condition that, in the opinion of the investigator, would be a contraindication for initiating pembrolizumab therapy.