Adoptive Cell Therapy Using Cancer Specific CD8+ Tumor Infiltrating Lymphocytes in Adult Patients With Solid Tumors

Inclusion Criteria

• Participants must have signed and dated a current IRB/IEC approved written informedconsent form in accordance with regulatory and institutional guidelines. Patientsmust have the ability to understand a written informed consent document, and thewillingness to sign it.

• Consent must be obtained before the performance of any protocol related proceduresthat are not part of normal patient care.

• Patients must have histologically confirmed advanced solid tumor that is metastaticor unresectable and who have progression of disease on standard therapy. Historicalpathology reports will suffice to meet this criterion, repeat biopsy confirmation isnot needed.

• Age >18 years

• At least one tumor nodule greater than or equal to 1 cm in long axis diameteramenable 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 firstdose 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 withGilbert's Syndrome who must have a total bilirubin ≤ 3.0 mg/dL; AST(SGOT) < 2.5X institutional upper limit of normal; ALT(SGPT) < 2.5 X institutional upperlimit of normal

• Adequate renal function: Serum creatinine < 1.5 x ULN, unless creatinineclearance ≥ 40 mL/min (measured or calculated using the Cockcroft-Gaultformula)

• Women of childbearing potential must not be pregnant and must avoid becomingpregnant while on treatment and for 6 months following treatment discontinuation.Men must agree to avoid fathering a child while on treatment and for 6 monthsfollowing 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 beforeparticipation in this protocol and have no therapeutic options with possibility ofcure or durable remission.

• Subjects with squamous cell carcinoma of the head and neck must have received aplatinum containing chemotherapy regimen for treatment of primary tumor in locallyadvanced, or metastatic settings and must have received an anti-PD-1/ PD-L1 asmonotherapy or in combination with chemotherapy.

• Subjects with melanoma must have received an anti-PD-1/ PD-L1 inhibitor asmonotherapy or in combination with anti-CTLA-4 inhibitor or anti-PD-1 in combinationwith anti-LAG-3 determined to have either primary or secondary CPI resistance.

• Subjects with tumors having known actionable molecular alterations such as BRAF andMEK for which FDA-approved medications are available must have progressed ondirected molecular therapy.

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases. Participants with brainmetastases are eligible if these have been treated and there is no MRI evidence ofprogression for at least 4 weeks after treatment is complete. There must also be norequirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/dayprednisone equivalents). Stable doses of anticonvulsants are allowed. Treatment forCNS metastases may include stereotactic radiosurgery (e.g. Gamma Knife, Cyber Knife,or equivalent) or neurosurgical resection. Patients who received whole brainradiation therapy are not eligible.

• Any condition including medical, emotional, psychiatric, or logistical that, in theopinion of the Investigator, would preclude the patient from adhering to theprotocol or would increase the risk associated with study participation or studydrug administration or interfere with the interpretation of safety results (e.g., acondition associated with diarrhea or acute diverticulitis).

• Prior malignancy active within the previous 3 years except for locally curablecancers that have been apparently cured, such as basal or squamous cell skin cancer,superficial bladder cancer, or localized carcinoma of the prostate, cervix, orbreast.

• Participants with an active, known or suspected autoimmune disease requiring activetreatment. Participants with type I diabetes mellitus, hypothyroidism requiring onlyhormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) notrequiring systemic treatment, or conditions not expected to recur in the absence ofan external trigger are permitted to enroll.

• Requirement for greater than physiological doses of corticosteroids (> 10 mg dailyprednisone equivalent)

• Requirement for other immunosuppressive medications including but not limited toanti-TNF antibodies, mycophenylate mofetil and methotrexate. Inhaled, intra-nasal ortopical steroids are permitted in the absence of active autoimmune disease.

• History of organ or tissue transplant that requires systemic use of immunesuppressive agents.

• Active infection requiring systemic therapy within 14 days prior to enrollment.

• Patients who have had chemotherapy, radiotherapy, biologics, other anti-neoplasticor investigational agents, and/or other antitumor treatment including immunotherapywithin 2 weeks (14 days) of Day -5, or those who have not recovered from adverseevents related to therapies administered more than 4 weeks (28 days) earlier, arenot eligible to enroll. All adverse events related to prior therapy must haveimproved to grade 1 or better before study participation.

• Focal radiotherapy (examples include SRS, Palliative or MRI-Linac) completed atleast 2 weeks (14 days) prior to the first dose study treatment are permitted toenroll.

• Patients with evidence of ischemia on exercise tolerance test, stress thalliumstudy, or baseline EKG are excluded.

• DLCO, FEV1 or FEV1/FVC less than 65% of predicted due to clinically significantunderlying pulmonary disease. For any pulmonary function test values less thanpredicted values, the PI will review, and document the patient's suitability forhigh-dose IL-2 therapy.

• Allergy to any of the antibiotics used in the cell production.

• Tumor harvest with no detectable DP CD8 TIL.