C-TIL051 in Non-Small Cell Lung Cancer

The goal of this Phase 1 clinical study is test tumor infiltrating lymphocytes (known as C-TIL051) with anti-PD1 therapy for subjects with refractory non-small cell lung cancer.The purpose of this study is to:Test the safety and ability for subjects to tolerate the TIL therapyMeasure to see how the NSCLC responds to the TIL therapyParticipants will be asked to:Provide a tumor sample prior to the start of any treatment which will be used to make the C-TIL051.Receive standard of care treatment until their lung cancer no longer respondsWhen necessary, the C-TIL051 will be manufactured by the sponsor and sent back to the siteSubject will then receive chemotherapy (called lymphodepletion) for 3 days followed by 2 days of restC-TIL051 will then be infused on day 0 followed by interleukin-2Pembrolizumab will be administered every 3 weeks for up to 2 years

Inclusion Criteria:Able to understand and give written informed consentHistologically and cytologically confirmed diagnosis of stage IV or recurrent non-small cell lung cancer (NSCLC) with adenocarcinoma or squamous histologyPlanned for treatment with an anti-PD1 agentTumor accessible by surgery, previously not irradiated and ≥ 1.5 cm in diameterMeasurable disease after resection of tumor by RECIST 1.1ECOG ≤ 1Expected survival > 6 monthsAdequate organ and marrow functionECHO, MUGA or cardiac stress test within past 6 months showing LVEF >50% and without evidence of reversible ischemiaPulmonary function tests within past 6 months showing DLCO >50% of predictedExclusion Criteria:Previous treatment with PD1/PDL1 inhibitor for metastatic disease, Immune checkpoint blockade (ICB) given as part of definitive therapy for stage Ib-III disease with surgery or after chemo/radiation is acceptable if last dose of ICB is at least 6 months prior to enrollment in this study.Known driver mutations such as EGFR, KRAS G12C, ALK, ROS1, BRAF V600E, RET, METex14, and NTRK alternations.Current or prior use of any immunosuppressive medications within 14 days before tumor harvestKnown active CNS metastases which are symptomaticHistory of leptomeningeal metastasesUncontrolled intercurrent illnessQTc ≥ 470 msKnown history of HIV+ or AIDS, hepatitis C, acute or chronic active hepatitis B or other serious chronic infectionLive vaccine within 30 days of tumor harvestHistory of allogeneic organ transplantHistory of primary immunodeficiencyHypersensitivity to anti-PD1 agent, cyclophosphamide, fludarabine, interleukin-2 or any excipientAny condition that may interfere with evaluation of study treatment, safety or study resultsActive infection that requires IV antibiotics within 7 days of tumor harvestUnresolved greater than grade 1 toxicity (CTCAE v5.0) from previous therapyHistory of interstitial pneumonitis of autoimmune etiology that is symptomatic or requires treatmentPulmonary disease history requiring escalating amounts of oxygen > 2LKnown autoimmune conditions requiring systemic immune suppression therapy other than low dose prednisone or equivalent.Other malignancy, other than cutaneous localized) that required active treatment in the last 2 years.Women who are pregnant or lactatingWomen of childbearing potential or fertile men unwilling to use effective contraception during study and 6 months after treatment