Clinical trial NCT05676749: C-TIL051 in Non-Small Cell Lung Cancer
Official title: C-TIL051 in Anti-PD1 Resistant Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Non Small Cell Lung Cancer
Lead sponsor: AbelZeta Inc.
Sponsor class: INDUSTRY
Collaborators: name: Nektar Therapeutics
First posted: 2023-01-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Calculate the Incidence of Adverse Events or Dose Limiting Toxicities
timeFrame: up to 24 months
Secondary outcomes:
measure: Calculate Objective Response Rate (ORR) of all Subjects
timeFrame: up to 36 months
measure: Calculate Duration of Response (DOR) of All Subjects
timeFrame: up to 36 months
measure: Calculate Progression Free Survival (PFS) for All Subjects
timeFrame: up to 36 months
measure: Determine Overall Survival (OS) of All Subjects
timeFrame: up to 36 months
Other outcomes:
measure: Collect Blood Samples to Measure the T-cells Before and After C-TIL051 Therapy
timeFrame: up to 24 months
measure: Collect Blood Samples to Measure Cytokines prior to and after C-TIL051 Therapy.
timeFrame: up to 24 months
measure: Collect Blood and Tumor Samples to Measure Circulating DNA
timeFrame: up to 24 months
measure: Collect Blood Samples to Measure Blood RNA
timeFrame: up to 24 months
measure: Perform Radiographic Imaging to Review Antitumor Activity Following Treatment
timeFrame: up to 24 months
measure: Collect and Analyze Tumor Samples for MicroOrganoSphereTM (MOS) Technology
timeFrame: up to 36 months
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: New Orleans
country: United States
facility: Ochsner MD Anderson Cancer Center
state: Louisiana
city: Raleigh
country: United States
facility: Duke Center for Cancer Immunotherapy
state: North Carolina
city: Pittsburgh
country: United States
facility: Allegheny Health Network-West Penn Hospital
state: Pennsylvania
Study officials:
References: