Phase I Randomized Open Label Trial Investigating Adoptive Transfer of CD39+CD103+CD8+ Tumor-isolated T Cells (AGX148) Alone or Combined With siRNA Modulation of PD-1 (AGX148/PH-762) in Patients With Advanced Solid Tumors
The subject of this study is the adoptive transfer of selected autologous tumor infiltrating lymphocytes (TIL) after in vitro expansion for the treatment of solid tumor malignancies. The TIL selection process is based on evidence showing that CD8+ TIL which co-express both CD39 and CD103 harbor the bulk of tumor-reactivity and that the remaining CD8 TIL is mainly composed of non-tumor reactive bystander cells. All of the expanded TIL that are produced (1-40 billion are expected) will be delivered in the form of a cell suspension to the participants by intravenous infusion. It is proposed that these selected TIL will produce a more potent and efficacious treatment of late-stage cancer.
• Participants must have signed and dated a current IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. Patients must have the ability to understand a written informed consent document, and the willingness to sign it.
• Consent must be obtained before the performance of any protocol related procedures that are not part of normal patient care.
• Patients must have histologically confirmed advanced solid tumor that is metastatic or unresectable and who have progression of disease on standard therapy. Historical pathology reports will suffice to meet this criterion, repeat biopsy confirmation is not needed.
• Age \>18 years
• At least one tumor nodule greater than or equal to 1 cm in long axis diameter amenable to surgical harvest as an out-patient procedure for DP CD8 TIL production.
• Patients must meet the laboratory criteria below within 28 days prior to the first dose of study treatment:
‣ Adequate Bone Marrow Function: WBC \>3,000/mcL; Absolute neutrophil count \>1,500/mcL; Hemoglobin \> 8 gm/dL; Platelets \>100,000/mcL
⁃ Adequate hepatic function: total bilirubin; ≤ 2.0 mg/dL except in patients with Gilbert's Syndrome who must have a total bilirubin ≤ 3.0 mg/dL; AST(SGOT) \< 2.5 X institutional upper limit of normal; ALT(SGPT) \< 2.5 X institutional upper limit of normal
⁃ Adequate renal function: Serum creatinine \< 1.5 x ULN, unless creatinine clearance ≥ 40 mL/min (measured or calculated using the Cockcroft-Gault formula)
• Women of childbearing potential must not be pregnant and must avoid becoming pregnant while on treatment and for 6 months following treatment discontinuation. Men must agree to avoid fathering a child while on treatment and for 6 months following the last dose of treatment.
• ECOG Performance Status 0-1 or equivalent Karnofsky score at the time of enrollment.
• Patients need to have received at least 1 prior line of systemic therapy before participation in this protocol and have no therapeutic options with possibility of cure or durable remission.
• Subjects with squamous cell carcinoma of the head and neck must have received a platinum containing chemotherapy regimen for treatment of primary tumor in locally advanced, or metastatic settings and must have received an anti-PD-1/ PD-L1 as monotherapy or in combination with chemotherapy.
• Subjects with melanoma must have received an anti-PD-1/ PD-L1 inhibitor as monotherapy or in combination with anti-CTLA-4 inhibitor or anti-PD-1 in combination with anti-LAG-3 determined to have either primary or secondary CPI resistance.
• Subjects with tumors having known actionable molecular alterations such as BRAF and MEK for which FDA-approved medications are available must have progressed on directed molecular therapy.