C-TIL051 in Non-Small Cell Lung Cancer

Metastatic Non Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05676749
• Other study ID #: CCI-2005
• Status: Recruiting
• Phase: Phase 1
• Start date: February 29, 2024
• Est. completion date: August 2027

Study information

• Verified date: February 2024
• Source: AbelZeta, Inc.
• Contact: Christine Cornwell
• Phone: 240-552-5870
• Email: christine.cornwell[@]abelzeta.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non Small Cell Lung Cancer

Intervention

Biological:
• C-TIL051
C-TIL051 given in combination with IL-15 (NKTR-255) and pembrolizumab

Locations

Country	Name	City	State
United States	Duke Cancer Institute	Raleigh	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AbelZeta, Inc.	Nektar Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Collect Blood Samples to Measure the T-cells Before and After C-TIL051 Therapy	Collect blood samples to review information about the t-cells present prior to lymphodepleting chemotherapy and after C-TIL051 therapy.	up to 24 months
Other	Collect Blood Samples to Measure Cytokines prior to and after C-TIL051 Therapy.	Collect blood samples and analyze for presence of cytokines at specified intervals before and after treatment with C-TIL051.	up to 24 months
Other	Collect Blood and Tumor Samples to Measure Circulating DNA	Collect blood and tumor samples and analyze for circulating DNA.	up to 24 months
Other	Collect Blood Samples to Measure Blood RNA	Collect blood samples and analyze for RNA sequencing	up to 24 months
Other	Perform Radiographic Imaging to Review Antitumor Activity Following Treatment	Measure by radiographical imaging (CT/MRI scan) and assess response by immune-related response criteria (irRC).	up to 24 months
Other	Collect and Analyze Tumor Samples for MicroOrganoSphereTM (MOS) Technology	Collect tumor sample and review outcome measures by MicroOrganoSphereTM (MOS) Technology.	up to 36 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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