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Clinical Trial 19122

Cancer Type: Thoracic
Interventions:Aldesleukin (Interleukin-2); BMS-936558 (Nivolumab); IL-2 (Interleukin-2); Interleukin-2; Nivolumab; Proleukin (Interleukin-2); TIL; cyclophosphamide; cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Phase I

  • Benjamin Creelan

Call 813-745-6100
or 1-800-679-0775

Study Title

A Phase I Clinical Trial Combining Nivolumab and Tumor Infiltrating Lymphocytes (TIL) for Patients with Advanced Non-Small Cell Lung Cancer


Investigators plan to study the safety, side effects, and benefits of tumor-infiltrating lymphocytes (TILs) when they are given with the drug nivolumab. Nivolumab is a type of immunotherapy - a drug that is used to boost the ability of the immune system to fight cancer, infection, and other diseases.


Primary Objectives: - To evaluate the safety and tolerability of TILs administered following initial progression on nivolumab therapy in combination with nivolumab in subjects with advanced non-small cell lung cancer (NSCLC). Secondary Objectives: - To evaluate the efficacy of TIL administered in combination with nivolumab in subjects with NSCLC by assessing the objective response rate (ORR) per modified RECIST v1.1 (mRECIST v1.1) at the biologically active dose of nivolumab. - To evaluate the efficacy of TIL administered in combination with nivolumab in subjects with NSCLC by assessing duration of response and progression-free survival (PFS). - To evaluate the T-cell persistence following TIL and nivolumab when administered in combination. Exploratory Objectives: - To characterize the pharmacodynamics and evaluate biomarkers of TIL and nivolumab from tumor tissue and peripheral blood. - To explore the antitumor activity of nivolumab in combination with TIL based on immune-related response criteria (irRC). - To evaluate the overall survival (OS) of subjects with select advanced solid tumors treated with TIL administered in combination with nivolumab.

Inclusion Criteria

  • Age >18 years
  • Able to understand and give written informed consent
  • Confirmed or suspected diagnosis of stage IV or recurrent non-small cell lung cancer (NSCLC). For suspected NSCLC, diagnosis must be histologically or cytologically confirmed prior to start of nivolumab treatment. Neuroendocrine cancers, or mixed neuroendocrine features in >10% of tumor cells, are excluded.
  • Tumor deemed accessible by metastasectomy (TIL harvest) which expects to yield >1.5 cm3 of resectable tumor amount.
  • Measurable disease, even after resection of applicable lesion for TIL harvest. Defined as ≥1 lesion that is ≥10 mm in one dimension by CT scan, MRI, or calipers on clinical exam.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Expected survival > 6 months
  • Patients with activating Epidermal Growth Factor Receptor (EGFR) mutation or Anaplastic Lymphoma Kinase (ALK) rearrangement which is expected to be responsive to available tyrosine kinase inhibitor therapy, must have been previously treated with an applicable tyrosine kinase inhibitor.
  • Adequate normal organ and marrow function in an assessment performed within 7 days (+ 3 day window) of enrollment, as outlined in the study protocol.
  • Positive screening Epstein Barr Virus (EBV) antibody titer on screening test.
  • Cardiac stress test within past 6 months without evidence of reversible ischemia.
  • Cardiac echocardiogram, stress test, or Multigated Acquisition Scan (MUGA) within past 6 months with demonstrated left ventricular ejection fraction (LVEF) > 50%
  • Pulmonary function tests within past 6 months showing Diffusion Lung Capacity for Carbon Monoxide (DLCO) >50% of predicted. Adjusted DLCO based on hemoglobin concentration should be used, if available.

  • Exclusion Criteria

  • More than 5 lines of prior systemic therapy in the preceding 3 years.
  • Any previous treatment with a PD-1 or PD-L1 inhibitor, including but not limited to: nivolumab, atezolizumab, pembrolizumab, or durvalumab.
  • Current or prior use of any immunosuppressive medications, such as corticosteroids, within 14 days before enrollment. a.) Oral hydrocortisone, only for the purposes of a documented and confirmed adrenal insufficiency diagnosis, permitted if ≤ 25 mg daily total dose. b.) Inhaled, intranasal, or topical corticosteroids are permitted.
  • Untreated brain metastases. Treated brain metastases with radiation or surgery are allowed if: ≤ 3 cm in size AND ≤ 4 in number AND there is no evidence of progressive disease, on brain imaging ≥ 28 days after last day of central nervous system (CNS) treatment.
  • History of leptomeningeal metastases.
  • Current or prior use of anticancer therapy before TIL collection: a.) Chemotherapy within past 4 weeks; b.) Tyrosine kinase inhibitor (TKI) within the past 1 week; c.) Investigational therapy within past 4 weeks or 4 half-lives, whichever is shorter.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than stable atrial fibrillation) and significant carotid artery stenoisis.
  • Known to be HIV positive, hepatitis B or C positive, or both Rapid Plasma Reagin (RPR) and Fluorescent Treponemal Antibody (FTA positive). (Hepatitis B surface or core antibody alone is not indicative of Hepatitis B Virus (HBV) infection).
  • Rapidly progressing tumors, as judged by the investigator.
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from electrocardiograms (ECGs) using Bazett's Correction
  • Known history of previous tuberculosis
  • Receipt of live attenuated vaccination within 30 days prior to first anticipated dose of nivolumab.
  • History of allogeneic organ transplant
  • History of primary immunodeficiency
  • History of severe hypersensitivity to nivolumab, cyclophosphamide, fludarabine, interleukin-2, or any excipient
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Active systemic infections requiring intravenous antibiotics within 1 week prior to enrollment.
  • Any unresolved toxicity (>CTCAE v4 grade 2) from previous anti-cancer therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included.
  • History of pneumonitis or drug-related inflammatory lung disease
  • Significant history of pulmonary disease that necessitates the use of supplemental oxygen, and patients with resting pulse oximetry less than 92% on room air.
  • Active or prior documented autoimmune disease within past 2 years. Patients with vitiligo, Grave's disease, limited site eczema, or limited site plaque psoriasis not requiring systemic treatment (within past 2 years), or other autoimmune conditions (not expected to recur), are allowed after approval from the medical monitor or Principal Investigator (PI).
  • Prior malignancies: must have had a ≥ 2-year disease-free interval, except: in situ carcinoma of the cervix, in situ ductal carcinoma of the breast, in situ prostate cancer, in situ bladder cancer. These must have been deemed stable and not expected to relapse. Early stage skin cancers, including basal, squamous cell cutaneous carcinoma, and melanoma, are permitted if previously treated with curative intent and not expected to relapse.
  • Pregnant or lactating.
  • Women of childbearing potential and fertile men unwilling to use effective contraception during study until 4 months after conclusion of the treatment period.