C-TIL051 in Non-Small Cell Lung Cancer
- Registration Number
- NCT05676749
- Lead Sponsor
- AbelZeta, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description C-TIL051 C-TIL051 C-TIL051 plus IL-15 (NKTR-255) and Pembrolizumab
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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 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.
Trial Locations
- Locations (4)
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Ochsner MD Anderson Cancer Center
🇺🇸New Orleans, Louisiana, United States
Duke Center for Cancer Immunotherapy
🇺🇸Raleigh, North Carolina, United States
Allegheny Health Network-West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States