T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer

NCT02133196 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 14010414-C-0104
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause non-small cell lung cancer (NSCLC) tumors to shrink and to see if this treatment is safe. Eligibility: \- Adults age 18-72 with NSCLC who have a tumor that can be safely removed. Design:

• Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed
• Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product.
• Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}
• Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Conditions

Squamous Cell Carcinoma; Advanced NSCLC; Adenosquamous Carcinoma; Advanced Non-Small Cell Lung Cancer; Adenocarcinoma

Keywords

Metastatic; Non-Small Cell Lung Cancer; NSCLC; Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Response rate

  Percentage of patients who have a clinical response to treatment (objective tumor regression)

  6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x 2 years, then per PI discretion

Secondary Outcomes (3)

• Phenotypic and functional characteristics of TIL

  2-4 years post cell infusion

• Frequency and severity of treatment-related adverse events

  30 days after end of treatment

• Feasibility of generating TIL from patients with NSCLC

  3-6 months post cell harvest

Study Arms (2)

1/High-Dose Aldesleukin

EXPERIMENTAL

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine plus young TIL plus high-dose Aldesleukin

Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Young TIL

2/Low-Dose Aldesleukin

EXPERIMENTAL

Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine plus young TIL plus low-dose Aldesleukin

Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Young TIL

Interventions

Aldesleukin DRUG

Aldesleukin 720,000 (Arm 1) or 72,000 (Arm 2) IU/kg IV (based on total body weight) over 15 minutes every 8 hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to a maximum of 9 doses in Arm 1 and 12 doses in Arm 2.

1/High-Dose Aldesleukin; 2/Low-Dose Aldesleukin

Young TIL BIOLOGICAL

Day 0: Cells will be infused intravenously (IV) on the Patient Care Unit over 20-30 minutes.

1/High-Dose Aldesleukin; 2/Low-Dose Aldesleukin

Fludarabine DRUG

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

1/High-Dose Aldesleukin; 2/Low-Dose Aldesleukin

Cyclophosphamide DRUG

Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with Mesna 15 mg/kg/day X 2 days over 1 hour.

1/High-Dose Aldesleukin; 2/Low-Dose Aldesleukin

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic (stage IV) or unresectable non-small cell lung cancer (including but not limited to squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinomas) with at least one lesion that is resectable for TIL generation. (Note: neuroendocrine tumors are not eligible.)
• Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
• All patients must have had at least one appropriate first line systemic therapy and progressed.
• Clinical performance status of ECOG 0 or 1.
• Age \>= 18 years of age and \<= 72 years of age.
• Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and for 12 months after the last dose of combined chemotherapy for individuals of childbearing potential (IOCBP) and for four months after treatment for individuals able to father a child.
• Willing to sign a durable power of attorney
• Able to understand and sign the Informed Consent Document
• I. Hematology:
• Absolute neutrophil count \> 1000/mm\^3 without support of filgrastim
• Normal WBC (\>= 2500/mm\^3).
• Hemoglobin \> 8.0 g/dl. Subjects may be transfused to reach this cut-off.
• Platelet count \>= 80,000/mm\^3
• j. Serology:
• Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.)

You may not qualify if:

• Participants who are nursing because of the potentially dangerous effects of the treatment on the infant.
• Ongoing need for pharmacological immunosuppression, including steroids
• Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active or uncompensated major medical illnesses
• Major bronchial occlusion or bleeding not amenable to palliation.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
• Disease and AIDS).
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• For select patients with a clinical history prompting cardiac evaluation: last known LVEF \<= 45%.
• For select patients with a clinical history prompting pulmonary evaluation: known FEV1 \<= 50%
• Any of the following will exclude patients from the high-dose aldesleukin arm, but may be eligible for the low-dose aldesleukin arm:
• Greater than 2 invasive thoracic procedures
• Poor exercise tolerance
• Greater than 66 years of age
• Clinically significant patient history which in the judgment of the Principal Investigator would compromise the patient s ability to tolerate high-dose.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Delbaldo C, Michiels S, Rolland E, Syz N, Soria JC, Le Chevalier T, Pignon JP. Second or third additional chemotherapy drug for non-small cell lung cancer in patients with advanced disease. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD004569. doi: 10.1002/14651858.CD004569.pub2.

  PMID: 17943820 BACKGROUND

• Boni C, Tiseo M, Boni L, Baldini E, Recchia F, Barone C, Grossi F, Germano D, Matano E, Marini G, Labianca R, Di Costanzo F, Bagnulo A, Pennucci C, Caroti C, Mencoboni M, Zanelli F, Prochilo T, Cafferata MA, Ardizzoni A; Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC). Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST). Br J Cancer. 2012 Feb 14;106(4):658-65. doi: 10.1038/bjc.2011.606. Epub 2012 Jan 12.

  PMID: 22240782 BACKGROUND

• Malekzadeh P, Pasetto A, Robbins PF, Parkhurst MR, Paria BC, Jia L, Gartner JJ, Hill V, Yu Z, Restifo NP, Sachs A, Tran E, Lo W, Somerville RP, Rosenberg SA, Deniger DC. Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers. J Clin Invest. 2019 Mar 1;129(3):1109-1114. doi: 10.1172/JCI123791. Epub 2019 Feb 4. No abstract available.

  PMID: 30714987 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Carcinoma, Adenosquamous; Adenocarcinoma; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

aldesleukin; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms, Complex and Mixed; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• James C Yang, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI SB Immunotherapy Recruitment Center

CONTACT

(866) 820-4505; irc@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2014
• First Posted: May 7, 2014
• Study Start: October 23, 2014
• Primary Completion (Estimated): October 23, 2027
• Study Completion (Estimated): October 23, 2027
• Last Updated: June 8, 2026

Record last verified: 2026-05-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)