Clinical Trial 24270

• Overview

  Study Title:

  A Phase 1/2 Study of KSQ-004EX, autologous Tumor Infiltrating Lymphocytes engineered to inactivate genes encoding SOCS1 and Regnase-1, in Patients with Select Advanced Solid Tumors

  Summary:

  Phase 1 is to find the recommended dose of KSQ-004EX to give to participants with advanced solid tumors. Phase 2 is to learn if KSQ-004EX at the recommended dose found in Phase1 can help to control advanced solid tumors. The safety and effects of KSQ-004EX will also be studied in both phases.

  Objective:

  Phase 1 Primary Objective: To evaluate the safety and tolerability of KSQ-004EX in adult patients with advanced solid tumors (melanoma, NSCLC, HNSCC, CRC, pancreatic cancer, and cervical cancer) Phase 2 Primary Objective: To assess the anti-tumor activity of KSQ-004EX as a single agent or in combination with pembrolizumab in patients with advanced malignant solid tumors

• Treatments

  Therapies:

  Cell Therapy; Chemotheraphy; Chemotherapy (NOS); Immunotherapy

  Medications:

  Cyclophosphamide (); Fludarabine (); IL-2 (Interleukin-2); KSQ-004EX (); Pembrolizumab (Keytruda)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Resectable lesion for KSQ-004EX manufacturing (tumor ≥ 1.5 cm2 or at least 5 core needle biopsies).
  • At least one measurable lesion per RECIST v1.1 (Eisenhauer 2009) following tumor resection for KSQ-004EX manufacturing Note: Lesions in previously irradiated areas should not be selected as a target lesion unless radiation treatment was ≥ 3 months prior, and there has been demonstrated disease progression in the lesion.
  • Age ≥ 18 years of age.
  • Life expectancy of ≥ 12 weeks.
  • Recovered to ≤ Grade 1 or Baseline toxicity (except alopecia, neuropathy, and endocrinopathies from prior immunotherapy) from prior therapy (per the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Adequate bone marrow function.
  • Adequate renal function defined as calculated creatinine clearance (Cockcroft-Gault) ≥ 40 mL/min.
  • Adequate hepatic function.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Signed and dated Institutional Review Board (IRB) approved informed consent form (ICF) before any protocol-directed Screening procedures are performed.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Prior organ allograft or prior cell therapy that included LDC or myeloablative chemotherapy regimen.
  • Known hypersensitivity to any component of KSQ-004EX or excipient including dimethyl sulfoxide, human serum albumin, LDC regimen (cyclophosphamide or fludarabine) or IL-2 (as applicable).
  • Hypersensitivity to antibiotics of the aminoglycoside group (eg, streptomycin, gentamicin) or penicillin.
  • Active, uncontrolled concurrent infection requiring IV antibiotics present at Screening.
  • Uveal and/or ocular melanoma.
  • Large cell neuroendocrine NSCLC (defined as pathology with >10% neuroendocrine components).
  • Participants with ascites.
  • Women who are pregnant or nursing.
  • Seropositive for human immunodeficiency virus (HIV) 1 or 2 or acquired immunodeficiency syndrome, or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) Note: Participants with positive HCV antibody may be eligible if HCV ribonucleic acid (RNA) is undetectable on a quantitative HCV RNA assay, following discussion with the drug provider (KSQ).
  • Any form of primary immunodeficiency (eg, Severe Combined Immunodeficiency Disease).
  • Any known clinically significant or concurrent acute liver disease, including viral hepatitis.
  • Previous solid organ or hematopoietic cell transplant.
  • Prolongation of QT/QTc interval (QTc interval > 480 msec) using the Frederica method of QTc analysis.
  • Unable to walk a distance of 80% predicted for age and sex or develop hypoxia (SPO2 > For participants receiving IL-2 only: evidence of ischemia on cardiac stress test.
  • > 80% stenosis based on carotid doppler ultrasound for patients with NSCLC and HNSCC with > 35 pack year smoking history.
  • Obstructive or restrictive pulmonary disease Note: Post-bronchodilator values: forced expiratory volume (FEV1)/forced vital capacity > 70% or FEV1 > 50% of predicted normal are required for study entry.
  • Suspected pneumonitis or interstitial lung disease (confirmed by radiography or computed tomography [CT]).
  • Treatment on another study with other investigational therapeutic interventional study within 28 days to start of LDC regimen.
  • Known additional malignancy that is active and/or progressive requiring treatment; exceptions including basal cell or squamous cell skin cancer, or other cancer for which the participants has been disease-free for at least 2 years.
  • Psychiatric illness/social situation that would limit compliance with study requirements, as determined by the Investigator.
  • Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of the study results, and in the judgement of the Investigator, would the participant inappropriate for the study.

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