Merkel Cell Carcinoma Clinical Trials

• Provide written informed consent, which includes understanding that there may be a need for intensive supportive care measures during the study and assessing willingness to undergo such measures, and written authorization for use and disclosure of protected health information.

• Patients must be ≥ than 18 years of age at the time of signing the informed consent form.

• Patients must have histologically or pathologically confirmed diagnosis of CSCC or MCC. Note: Mixed histology is allowed. Note: Neuroendocrine cancer that is clinically considered to be related to a cutaneous primary (MCC) or induced by sun damage (per investigator assessment) is allowed.

• Patients must have unresectable, recurrent, or metastatic disease.

• Patients must have a documented radiographic or clinical disease progression after treatment with ICI (including anti-PD-1 and anti-PD-L1) if it is used in the palliative setting. In patients who received ICI in the neoadjuvant or adjuvant setting, recurrence should have occurred within 6 months from the last treatment with ICI.

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 in the investigator's opinion (Appendix B).

• Patients must have at least 1 resectable lesion (or aggregate lesions) with an expected minimum of 1.5 cm diameter in the short axis for TIL production. Note: If a lesion that is considered for TIL harvest is within a previously irradiated field, the lesion must have demonstrated radiographic or clinical progression prior to harvest, and the irradiation must have been completed at least 6 months prior to enrollment.

• Patients must be expected to have at least 1 remaining measurable lesion as defined by RECIST v1.1 or evaluable (radiographically or on clinical examination) following tumor harvest for TIL manufacturing and production that is documented at screening with the following considerations:

‣ Lesions in a previously irradiated areas should not be selected as target lesions unless progression has been demonstrated in those lesions and the irradiation has been completed at least 6 months prior to enrollment.

⁃ Patients who have only one site of disease may be enrolled if they have a lesion th can be partially resected for TIL harvest, and the remaining portion of the lesion is measurable or evaluable.

• Patients must have the following hematologic parameters:

‣ Absolute neutrophil count (ANC) ≥ 1000/mm3

⁃ Hemoglobin ≥ 8.0 g/dL and have not received transfusion of packed red blood cells within 7 days.

⁃ Platelet count ≥ 100,000/mm3

• Patients must have an adequate organ function with the following laboratory test values:

‣ Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN); and for patients with liver metastases ≤ to 5 times ULN.

⁃ Total bilirubin ≤ 2 mg/dL; patients with Gilbert's Syndrome ≤ to 3 mg/dL.

⁃ Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault formula at Screening.

• Patients must have a left ventricular ejection fraction (LVEF) ≥ 45% and be New York Heart Association (NYHA) Class 1 or 2. A cardiac stress test is required for patients who have significant ischemic heart disease, or clinically significant unstable arrythmias; the cardiac stress test must demonstrate no irreversible wall movement abnormality. Patients with an abnormal cardiac stress test may be enrolled if they have adequate ejection fraction and cardiology clearance.

• Patients must have adequate pulmonary function within 2 months from enrollment.

∙ Patients require pulmonary function testing (PFT) if they have any of the following:

• History of cigarette smoking of ≥ 20 pack-years

• Ceased smoking within the past 2 years or still smoking.

• History of chronic obstructive pulmonary disease (COPD)

• Any signs or symptoms of significant respiratory dysfunction.

∙ Post-bronchodilator required pulmonary test results:

• Forced expiratory volume (FEV1)/ forced vital capacity (FVC) \> 70%. Or

• FEV1 \> 50% of predicted normal value. Note: If a patient is unable to perform reliable spirometry due to abnormal upper airway anatomy (i.e., tracheostomy), a 6-minute walk test may be used to assess pulmonary function. Patients must be able to walk a distance at least 80% of predicted for age and sex with no evidence of hypoxia at any point during the test (i.e., saturation of peripheral oxygen \[SpO2\] must remain ≥ 89%).

‣ Patients must have completed or discontinued systemic therapy ≥ 21 days prior to tumor harvest. Note: Patients are allowed to have palliative radiation or systemic therapy after tumor harvest and before NMA-LD but there should be at least 7 days between discontinuation of palliative treatment and start of NMA-LD.

⁃ Patients must have recovered from all prior anticancer TRAEs to Grade ≤ 1 (per CTCAE v5.0) with the exceptions of vitiligo, alopecia or neuropathy. Patients with irreversible toxicity that are properly managed (such as with endocrinopathy treatment with hormone replacement therapy) may qualify for the study regardless of grade of TRAEs.

⁃ Patients of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and for 12 months after receiving all protocol-related therapy (Appendix C). Additionally, males may not donate sperm and females may not donate eggs during the required contraception period.

∙ Approved methods of birth control include:

• Combined (estrogen- and progesterone- containing) hormonal birth control associated with inhibition of ovulation: oral, intravaginal, transdermal.

• Progesterone-only hormonal birth control associated with inhibition of ovulation:

∙ oral, injectable, implantable.

• Intrauterine device (IUD)

• Intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion

• Vasectomy

• True absolute sexual abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar ovulation, symptothermal, post-ovulation methods) is not acceptable.