TIL Therapy in Non-small-cell Lung Cancer (NSCLC) Patients

Non-Small Cell Lung Cancer Clinical Trial

— BaseTIL-02  

Official title:

A Phase II Trial of Adoptive Cell Therapy With Tumor-infiltrating Lymphocytes in Patients With Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06455917
• Other study ID #: 2024-00254; th22Laeubli
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: December 2029

Study information

• Verified date: June 2024
• Source: University Hospital, Basel, Switzerland
• Contact: David König, MD
• Phone: +41 61 265 5074
• Email: david.koenig[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim of the study is to investigate the efficacy and safety of Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in NSCLC patients in a phase II clinical trial.

Description:

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a personalized immunotherapy. In patients with advanced Non-Small Cell Lung Cancer (NSCLC), a phase I clinical trial has investigated TIL-ACT in patients who progressed during ICI-treatment.

For TIL-ACT, tumor-specific T cells are expanded from excised tumor samples and stimulated in cell culture with interleukin-2 (IL-2). The resulting autologous TILs are then re-infused to the patient after a non-myeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Activation of TILs in the patient is then supported by IL-2 administration.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 2029
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Ability of the patient to understand the purpose of the study, provide signed and dated informed consent prior to performing any protocol-related procedures (including screening evaluations), and be able and willing to comply with the study procedures.

2. Age = 18 years.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (cf. Appendix).

4. Histologically confirmed NSCLC.

5. Disease progression after at least one standard therapy and without any approved curative-intended treatment option.

6. Accessible tumor lesion/metastasis for tumor collection.

7. Willingness of the patient to undergo a surgical intervention (eg, surgical resection and/or biopsy) to collect one or more tumor lesions/metastases.

8. Adequate organ function (pulmonary, cardiovascular, hematological, hepatic, and renal function) per investigator's judgment. Cardiac stress testing is required for all patients with underlying cardiac conditions and patients with age = 50 years.

9. Negative serum pregnancy test in women of childbearing potential, in peri-menopausal women and in women with less than 2 years of menopause.

Exclusion Criteria:

1. Active central nervous system (CNS) metastases. Patients with stable CNS metastases = 1 month after definitive treatment (eg, surgery and/or radiotherapy) are eligible.

2. Participants with an active second malignancy.

3. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol, including autoimmune or immunodeficient conditions, significant pulmonary disease, significant cardiac and/or vascular disease per investigator's judgment.

4. Prior immune-related adverse events that would preclude re-challenge with an immune checkpoint inhibitor or immunomodulatory agent per investigator's judgment.

5. Immunosuppressive treatment that would preclude the patient from any of the study therapies per investigator's judgment.

6. Severe active infections or uncontrolled infectious conditions requiring treatment.

7. Any other conditions/diseases, allergies, dysfunctions, and/or findings, that would contraindicate the use of any of the study interventions or therapies.

8. Contraindication for any of the planned measures, interventions and/or treatments.

9. Pregnant or breastfeeding women, or female subject who are not willing to use an acceptable, highly effective method of contraception until the End-of-Study visit.

10. Known hypersensitivity to any of study therapies or drugs used for TIL production.

11. Known human immunodeficiency virus (HIV) infection (or tests positive for HIV 1 or 2 at Screening).

12. Known hepatitis B or hepatitis C infection.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Combination of TIL Transfer and low dose IL-2
The study uses a personalized IMP, i.e. TIL product and in combination with IL-2 treatment. TIL transfer: transfer of the TIL product (i.v., 1 infusion of 5 x109 - 2 x1011 lymphocytes, day 0). Interleukin-2 (IL-2) therapy: administration of Aldesleukin (600'000 IU/kg body weight, i.v., every 8 hours for up to 15 doses).

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel	Basel-Stadt

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free rate at 6 months after Tumor-infiltrating lymphocytes transfer.	Progression-free rate (PFR) (RECIST v1.1 / iRECIST) at 6 months after TIL transfer, defined by the Kaplan-Meier estimator for progression-free survival (RECIST v1.1 / iRECIST) at 6 months (+/- 4 weeks as we allow this interval in the tumor assessment at 6 months).	5-7 months after TIL transfer
Secondary	Progression-free survival (PFS)	The progression-free survival (PFS) is defined as the time from registration to objective tumor progression (determined by local investigators), or death due to any cause, whichever occurred first. PFS time for patients who have not progressed or died will be censored at the time of the last tumor assessment	up to one year after TIL transfer
Secondary	Overall survival (OS)	OS is defined as the time from registration to the date of death due to any cause	up to one year after TIL transfer
Secondary	Severity of adverse events (CTCAE v5.0 criteria)	Severity of adverse events (CTCAE v5.0 criteria) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2; CTCAE (Common Terminology Criteria for Adverse Events): Grade 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal.	up to one year after TIL transfer
Secondary	Objective response rate (ORR)	ORR is defined as the proportion of patients with a best overall response of partial response or better (assessed by the local investigators	up to one year after TIL transfer
Secondary	Duration of response (DOR)	DOR is defined as the time from the first documented response and the date of the first documented tumor progression, death, or the last tumor assessment that occurred before subsequent therapy. DOR time for responders who have not progressed or died will be censored at the time of last tumor assessment	up to one year after TIL transfer
Secondary	Frequency of adverse events (number)	Frequency of adverse events (number) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2	up to one year after TIL transfer
Secondary	Incidence of adverse events (%)	Incidence of adverse events (%) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with IL-2	up to one year after TIL transfer