Metastatic Non Small Cell Lung Cancer
Conditions
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: 1. Test the safety and ability for subjects to tolerate the TIL therapy 2. 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.
Interventions
BIOLOGICALC-TIL051
C-TIL051 given in combination with IL-15 (NKTR-255) and pembrolizumab
Sponsors
Nektar Therapeutics
AbelZeta Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Calculate the Incidence of Adverse Events or Dose Limiting Toxicities | up to 24 months | Record the incidence and severity of all adverse events or dose limiting toxicities that occur according to CTCAE criteria V5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Calculate Objective Response Rate (ORR) of all Subjects | up to 36 months | Measure by radiographical imaging (CT/MRI scan) the objective response rate using RECIST 1.1 |
| Calculate Duration of Response (DOR) of All Subjects | up to 36 months | Measure by radiographical imaging (CT/MRI scan) the length of response in time. |
| Calculate Progression Free Survival (PFS) for All Subjects | up to 36 months | Measure by radiographical imaging (CT/MRI scan) the length of time to progression of disease. |
| Determine Overall Survival (OS) of All Subjects | up to 36 months | Measure by physical exam and contact reports the overall survival for all subjects following C-TIL051 treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Collect Blood Samples to Measure the T-cells Before and After C-TIL051 Therapy | up to 24 months | Collect blood samples to review information about the t-cells present prior to lymphodepleting chemotherapy and after C-TIL051 therapy. |
| Collect and Analyze Tumor Samples for MicroOrganoSphereTM (MOS) Technology | up to 36 months | Collect tumor sample and review outcome measures by MicroOrganoSphereTM (MOS) Technology. |
| Collect Blood Samples to Measure Cytokines prior to and after C-TIL051 Therapy. | up to 24 months | Collect blood samples and analyze for presence of cytokines at specified intervals before and after treatment with C-TIL051. |
| Collect Blood and Tumor Samples to Measure Circulating DNA | up to 24 months | Collect blood and tumor samples and analyze for circulating DNA. |
| Collect Blood Samples to Measure Blood RNA | up to 24 months | Collect blood samples and analyze for RNA sequencing |
| Perform Radiographic Imaging to Review Antitumor Activity Following Treatment | up to 24 months | Measure by radiographical imaging (CT/MRI scan) and assess response by immune-related response criteria (irRC). |
Countries
United States
Outcome results
None listed