C-TIL051 in Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The goal of this Phase 1 clinical study is test tumor infiltrating lymphocytes (known as C-TIL051) with NKTR-255 and 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 therapy Measure to see how the NSCLC responds to the TIL therapy Participants 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 responds When necessary, the C-TIL051 will be manufactured by the sponsor and sent back to the site Subject will then receive chemotherapy (called lymphodepletion) for 3 days followed by 2 days of rest C-TIL051 will then be infused on day 0 followed by NKTR-255 (IL-15) about 12 to 24 hours later Pembrolizumab will be administered every 3 weeks for up to 2 years NKTR-255 is a novel polymer-conjugated human IL-15 receptor agonist molecule designed to increase the proliferation and survival of memory CD8+ T cells and enhance the formation of long-term immunological memory which may lead to sustained anti-cancer immune response. The combination of NKTR 255 and TIL's could improve proliferation and persistence of cellular therapies leading to enhanced anti-tumor activity.

Official Title
-----------------
C-TIL051 in Anti-PD1 Resistant Metastatic Non-Small Cell Lung Cancer

Conditions
-----------------
Metastatic Non Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Biological: C-TIL051


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to understand and give written informed consent Histologically and cytologically confirmed diagnosis of stage IV or recurrent non-small cell lung cancer (NSCLC) with adenocarcinoma or squamous histology Planned for treatment with an anti-PD1 agent Tumor accessible by surgery, previously not irradiated and ≥ 1.5 cm in diameter Measurable disease after resection of tumor by RECIST 1.1 ECOG ≤ 1 Expected survival > 6 months Adequate organ and marrow function ECHO, MUGA or cardiac stress test within past 6 months showing LVEF >50% and without evidence of reversible ischemia Pulmonary function tests within past 6 months showing DLCO >50% of predicted Exclusion 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, ALK, ROS1, RET, METex14, and NTRK alterations. Current or prior use of any immunosuppressive medications within 14 days before tumor harvest Known active CNS metastases which are symptomatic History of leptomeningeal metastases Uncontrolled intercurrent illness Known history of HIV+ or AIDS, hepatitis C, acute or chronic active hepatitis B or other serious chronic infection Live vaccine within 30 days of tumor harvest History of allogeneic organ transplant History of primary immunodeficiency Hypersensitivity to anti-PD1 agent, cyclophosphamide, fludarabine, interleukin-2, gentamicin, or any excipient Any condition that may interfere with evaluation of study treatment, safety or study results Active infection that requires IV antibiotics within 7 days of tumor harvest Unresolved greater than grade 1 toxicity (CTCAE v5.0) from previous therapy History of interstitial pneumonitis of autoimmune etiology that is symptomatic or requires treatment Pulmonary disease history requiring escalating amounts of oxygen > 2L Known 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 lactating Women of childbearing potential or fertile men who are unwilling to use effective contraception during study and 6 months after treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C-TIL051<br>C-TIL051 plus IL-15 (NKTR-255) and Pembrolizumab | Biological: C-TIL051<br>* C-TIL051 given in combination with IL-15 (NKTR-255) and pembrolizumab<br>* Other names: NKTR-255;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculate the Incidence of Adverse Events or Dose Limiting Toxicities | Record the incidence and severity of all adverse events or dose limiting toxicities that occur according to CTCAE criteria V5.0 | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculate Objective Response Rate (ORR) of all Subjects | Measure by radiographical imaging (CT/MRI scan) the objective response rate using RECIST 1.1 | up to 36 months | 
| Calculate Duration of Response (DOR) of All Subjects | Measure by radiographical imaging (CT/MRI scan) the length of response in time. | up to 36 months | 
| Calculate Progression Free Survival (PFS) for All Subjects | Measure by radiographical imaging (CT/MRI scan) the length of time to progression of disease. | up to 36 months | 
| Determine Overall Survival (OS) of All Subjects | Measure by physical exam and contact reports the overall survival for all subjects following C-TIL051 treatment. | up to 36 months |