Clinical Trial 23098

• Overview

  Study Title:

  A Phase IB Clinical Study of TBio-4101 (Autologous Selected and Expanded Tumor-Infiltrating Lymphocytes [TIL]) and Pembrolizumab with or without chemotherapy in Patients with Recurrent/Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

  Summary:

  Phase 1b open-label study to evaluate the safety of selected TIL (TBio-4101) delivered after lymphodepleting chemotherapy and followed by intravenous (IV) bolus aldesleukin (IL-2) and pembrolizumab for patients with advanced HNSCC who have initially progressed on pembrolizumab or pembrolizumab/platinum chemotherapy.

  Objective:

  Primary Objective: Define the safety and tolerability of NMA-LD chemotherapy, TBio-4101, aldesleukin (IL-2), and pembrolizumab administered following initial progression on pembrolizumab or pembrolizumab/platinum therapy in participants with HNSCC. Secondary Objectives: Determine the overall response rate (ORR) of TBio-4101 administered in combination with pembrolizumab. Determine the durable response rate (DRR). Determine the duration of response (DoR) and disease control rate (DCR). Assess the feasibility of TBio-4101. Exploratory Objectives: To characterize the pharmacodynamics and evaluate biomarkers of TBio-4101 and pembrolizumab from tumor tissue and peripheral blood. Evaluate time to progression (TTP), progression-free survival (PFS), and overall survival (OS). To explore the antitumor activity of pembrolizumab in combination with TBio-4101 based on immune-related response criteria (irRC). Explore potential significance of T cell phenotype including TCR clonality and diversity and tumor antigen reactivity of TBio-4101 as they correlate with clinical outcome. Evaluate TBio-4101 engraftment, persistence, activation, phenotype, transcriptome profile and tumor infiltration and correlate these findings with clinical outcome. Compare baseline and on treatment determinants in the tumor by pathology and genomic analysis of pre- and on-treatment biopsies with clinical response.

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS); Immunotherapy

  Medications:

  5-fluorouracil (); Aldesleukin (Interleukin-2); IL-2 (Interleukin-2); Paraplatin (carboplatin); Pembrolizumab (Keytruda); TBio-4101 (); carboplatin (); cisplatin (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Inclusion Criteria:
  • Participants must have pathologically confirmed, recurrent, unresectable or metastatic solid tumors of Head and Neck Squamous Cell Carcinomas (HNSCC), excluding nasopharyngeal and nasal cavity carcinomas, and must have received no prior treatment for metastatic disease.
  • Participants must have at least 1 cm3 (1.1 g) of viable tumor tissue amenable for resection for Tumor-Infiltrating Lymphocyte (TIL) generation, and at least one target tumor that can be used for response assessment by RECIST 1.1 and iRECIST criteria and for mandatory translational tumor biopsy (where applicable).
  • Participants must be willing and able to undergo an apheresis procedure.
  • Any systemic therapy, including anti-cancer monoclonal antibodies, must have been completed at least 3 weeks prior to TIL harvest or apheresis, whichever is earlier, and any prior therapy-related adverse events (AEs) must have resolved to Grade less than or equal to 1 except for alopecia and vitiligo. Neuropathy and anemia must have resolved to Grade less than or equal to 2.
  • Participants must be age 18-75 years at the time of TIL harvest.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Participants given pembrolizumab monotherapy must have a composite positive score greater than or equal to 1.
  • Participants must demonstrate adequate organ and marrow function.
  • Participants must be seronegative for Human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, and hepatitis C (HCV) antibody (if HCV antibody positive, must be tested for HCV RNA, which must be negative to be eligible).
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.

• Exclusion Criteria

  Exclusion Criteria:
  • Participants with a known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Participants who have received prior cell therapy or prior organ transplant.
  • Participants who have received any previous treatment with a PD-1 or PD-L1 inhibitor, including but not limited to: nivolumab, atezolizumab, pembrolizumab, avelumab, or durvalumab.
  • Participants who are receiving any other investigational agents.
  • Participants who have a history of severe immediate hypersensitivity reaction to the study agents or any of their constituents.
  • Participants who have a severe allergy to gentamicin.
  • Participants who have received a live or live-attenuated vaccine within 30 days prior to TIL harvest or apheresis, whichever is earlier. Note: Administration of killed vaccines is allowed.
  • Participants who require chronic anti-coagulant therapy that cannot either be discontinued or changed to an anti-coagulant with a relatively short half-life, such as a low molecular weight heparin.
  • Participants with either a primary immunodeficiency disorder (i.e., severe combined immunodeficiency syndrome) or acquired immunodeficiency disorders (such as HIV/AIDS).
  • Participants with a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to TIL harvest or apheresis, whichever is earlier.
  • Participants with a serious cardiac condition, such as uncontrolled hypertension, concurrent congestive heart failure, prior history of Class III/IV cardiac disease (New York Heart Association [NYHA]), left ventricular ejection fraction (LVEF) 60 years of age must undergo cardiology clearance exam and cardiac stress test, unless performed within the last 6 months and there has been no clinical change with respect to heart function.
  • Participants with a forced expiratory volume (FEV1) less than or equal to 60% of predicted value and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected) > Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Participants with active infections requiring parenteral antibiotics that, in the opinion of the Investigator, would increase the risk of adverse events during TIL harvest or apheresis or start of NMA-LD chemotherapy.
  • Participants with a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
  • Pregnant women are excluded from this study.

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