Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC

NCT05681780 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MCC-21971
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the effect of a special preparation of cells, called tumor-infiltrating lymphocytes (TIL) stimulated with CD40L, when given with the drug nivolumab, for patients with EGFR, ALK, ROS1, or HER2-genomically altered lung cancer.

Conditions

Recurrent Non Small Cell Lung Cancer; Non Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Keywords

Lung Cancer; Tumor-Infiltrating Lymphocytes; EGFR Mutation; ALK Rearrangement; ROS1 Rearrangement; ERBB2 Mutation; HER2 Exon 20 Mutation

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AE)

  To characterize the safety profile of CD40L-augmented TIL administered with nivolumab.

  Up to 18 Months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 5 Years

• Duration of Response (DOR)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 Years

Study Arms (1)

TIL+ Nivolumab

EXPERIMENTAL

Nivolumab infusion every 3 weeks prior to lymphodepletion chemotherapy with cyclophosphamide/fludarabine, TIL infusion and interleukin-2. Then nivolumab infusion every 4 weeks up to 12 months.

Biological: Tumor-infiltrating Lymphocytes (TIL); Drug: Nivolumab; Drug: Cyclophosphamide; Drug: Fludarabine; Other: Tumor-infiltrating Lymphocyte Therapy; Drug: Interleukin-2 (IL2)

Interventions

Nivolumab DRUG

Nivolumab (Opdivo®), 360 mg, IV infusion every 3 weeks prior to TIL infusion, and then after TIL infusion 480 mg ever 4 weeks for up to 12 months.

Also known as: Opdivo

TIL+ Nivolumab

Cyclophosphamide DRUG

Cyclophosphamide will be administered on days -7 and -6.

Also known as: Cytoxan

TIL+ Nivolumab

Fludarabine DRUG

Fludarabine will then be infused per institutional standard on Days -7 to -3.

Also known as: Fludara

TIL+ Nivolumab

Tumor-infiltrating Lymphocyte Therapy OTHER

On day 0, all patients will receive a dose infusion TIL cells.

Also known as: TIL

TIL+ Nivolumab

Interleukin-2 (IL2) DRUG

Participants will receive IL-2 for up to 6 doses, based on participants tolerance and investigator judgement. This will be given after the infusion of the T-cells.

Also known as: IL2

TIL+ Nivolumab

Tumor-infiltrating Lymphocytes (TIL) BIOLOGICAL

Tumor harvest for TIL growth in the lab: A sample of the participant's tumor will be collected and sent to the lab for TIL growth. TIL will be prepared and cryopreserved.

Also known as: TIL

TIL+ Nivolumab

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years
• Diagnosis of stage IV or recurrent non-small cell lung cancer (NSCLC) with an activating genomic alteration within either: EGFR, ALK, ROS1, or ERBB2 receptor tyrosine kinase domains
• ECOG performance status of 0 or 1
• Expected survival ≥ 4 months
• Participants must have had disease progression after at least one prior line of systemic therapy for NSCLC, including appropriate prior targeted therapy for cases in which a targeted therapy is conventionally used for this genomic alteration, prior to initiating nivolumab trial therapy
• Measurable disease, not including any lesion that is used for TIL harvest, prior to initiation of nivolumab trial therapy
• In accordance with the criteria above, safely accessible tumor for TIL harvest by excisional biopsy expected to yield 1.5 cm3 of tissue, in aggregate
• Participants with known brain metastases are eligible for study enrollment if the brain metastases have received appropriate central nervous system-directed therapy or are found to be clinically stable ≤ 10 mm when comparing scans obtained during the screening period with a scan obtained ≥28 days prior, or if the treating physician determines that immediate CNS-specific treatment is not required prior to the first cycle of therapy. Please also refer to eligibility section on corticosteroids below.
• Adequate normal organ and marrow function as defined below:
• a. Hemoglobin ≥ 9.0 g/dL, with transfusions permissible;
• b. Absolute neutrophil count (ANC) ≥ 1000 per mm3);
• c. Platelet count ≥ 75,000 per mm3, without platelet transfusions for 7 days;
• d. Prothrombin Time ≤ 1.7x the institutional upper limit of normal (ULN), unless participant is receiving intended anticoagulant therapy.
• e. Serum bilirubin ≤ 2.0x the institutional ULN, or ≤ 4.0x ULN if confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology) with PI approval.
• f. AST/ALT ≤ 2.5x institutional ULN unless liver metastases are present, in which case it must be ≤ 5x ULN

You may not qualify if:

• No more than six prior lines of systemic therapy for NSCLC
• No prior PD-1 or PD-L1 inhibitor treatment for metastatic NSCLC. Examples of inhibitors include: nivolumab, atezolizumab, pembrolizumab, avelumab, cemplimumab, spartalizumab, or durvalumab.
• Participants with rapidly progressing tumors, as judged by the investigator
• Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, limited site eczema, or limited site plaque psoriasis not requiring systemic treatment (within the past 2 years), or other autoimmune conditions which are not expected to recur, are allowed after approval from the medical monitor or PI
• Active leptomeningeal or pachymeningeal metastases, or carcinomatous meningitis. This is due to prognostic implications and timeline for cell therapy
• Has a diagnosis of primary immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
• a. Oral hydrocortisone, only for the purposes of a documented adrenal insufficiency diagnosis, is permitted if ≤ 25 mg daily total dose
• b. Inhaled, intranasal, or topical corticosteroids are permitted
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation or supraventricular tachycardia), and significant ≥85% carotid artery stenosis
• Unresolved toxicity (grade 2) from previous anti-cancer therapy. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy)
• Mean QT interval corrected for heart rate (QTc) ≥480 ms calculated from electrocardiograms (EKGs) using Bazett's Correction
• Participants with active systemic infections requiring intravenous antibiotics within 1 week prior to nivolumab. Prophylactic, empiric, or suppressive antibiotics are permitted with sponsor approval
• History of allogeneic organ transplant
• Participants with psychiatric illness/social situations that would limit compliance with study requirements
• Participants with a history of anaphylaxis to beta-lactam antibiotics. Patients may be evaluated for reported history by conducting a history and physical, and a skin test/challenge where appropriate under medical guidance

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Publications (1)

• Creelan BC, Wang C, Teer JK, Toloza EM, Yao J, Kim S, Landin AM, Mullinax JE, Saller JJ, Saltos AN, Noyes DR, Montoya LB, Curry W, Pilon-Thomas SA, Chiappori AA, Tanvetyanon T, Kaye FJ, Thompson ZJ, Yoder SJ, Fang B, Koomen JM, Sarnaik AA, Chen DT, Conejo-Garcia JR, Haura EB, Antonia SJ. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial. Nat Med. 2021 Aug;27(8):1410-1418. doi: 10.1038/s41591-021-01462-y. Epub 2021 Aug 12.

  PMID: 34385708 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Nivolumab; Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukin-2

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors

Study Officials

• Ben Creelan, MD, MS

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ben Creelan

CONTACT

813-745-4541; Ben.Creelan@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2022
• First Posted: January 12, 2023
• Study Start: March 10, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)