ITIL-306 in Advanced Solid Tumors

A Phase 1a/1b, Open-Label, Multicenter Study Evaluating the Safety and Feasibility of ITIL-306 in Subjects With Advanced Solid Tumors

ITIL-306-201 is a phase 1a/1b, multicenter, clinical trial evaluating the safety and feasibility of ITIL-306 in adult participants with advanced solid tumors whose disease has progressed after standard therapy. ITIL-306 is a cell therapy derived from a participant's own tumor-infiltrating immune cells (lymphocytes; TILs) and contains a unique molecule designed to increase TIL activity when it encounters folate receptor α (FOLR1) on the tumor.

Key Inclusion Criteria:

• Histologically documented advanced (metastatic and/or unresectable) disease as appropriate per cohort.

  • Phase 1a Dose Escalation: High-grade serous epithelial carcinoma of the ovary, fallopian tube, or peritoneum, adenocarcinoma of the lung, or clear-cell renal cell carcinoma.

  • Phase 1b Expansion:

    • Cohort 1: High grade serous, endometrioid, or clear cell epithelial carcinoma of the ovary, fallopian tube, or peritoneum.
    • Cohort 2: Squamous-cell carcinoma or adenocarcinoma of the lung.
    • Cohort 3: Clear cell or papillary RCC.

• Disease must have unequivocally progressed during or after at least 1 prior line of systemic therapy that must include the following parameters (by indication):

  • Phase 1a dose escalation and Phase 1b Cohort 1: Participants with EOC whose disease has progressed during or after 1 prior line (at least 4 cycles) of platinum-based chemotherapy and had disease progression within 6 months from the last dose of the platinum agent. Participants who received 2 or more lines of platinum therapy must have disease which has progressed on or within 6 months after the date of the last dose of the platinum agent. Participants with BRCA-mutated EOC must have received previous PARP inhibitor therapy.
  • Phase 1a dose escalation and Phase 1b Cohort 2: Participants with NSCLC whose disease has progressed after 1 prior line of platinum-based doublet chemotherapy and a CPI. Participants with targetable mutations (e.g. EGFR/ALK/KRAS) are required to have progressed on targeted therapy in addition to a platinum-based doublet chemotherapy
  • Phase 1a dose escalation and Phase 1b Cohort 3: Participants with RCC whose disease has progressed after 1 prior line of antiangiogenic therapy and a PD-1-axis inhibitor.

• Medically suitable for surgical resection of tumor tissue

• Following tumor resection for TIL harvest, will have, at minimum, 1 remaining measurable lesion as identified by CT or MRI per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Adequate bone marrow and organ function

Key Exclusion Criteria:

• History of another primary malignancy within the previous 3 years

• Phase 1a:

  • EOC of the following subtypes: low-grade, endometrioid, clear cell, mucinous, sarcomatous, or mixed.
  • NSCLC of the following subtypes: squamous, neuroendocrine differentiation.
  • RCC of the following subtypes: nonclear-cell RCC

• Phase 1b:

  • Cohort 1: Participants with mucinous, sarcomatous, and low-grade EOC.
  • Cohort 2: Participants with small cell lung cancer, or NSCLC with neuroendocrine differentiation
  • Cohort 3: Participants with nonclear-cell RCC, except papillary RCC

• Previously received an allogeneic stem cell transplant or organ allograft

• Previously received TIL or engineered cell therapy (eg, CAR T-cell)

• Significant cardiac disease

• Stroke or transient ischemic attack within 12 months of enrollment

• History of significant central nervous system (CNS) disorder

• Symptomatic and/or untreated CNS metastases

• History of significant autoimmune disease within 2 years prior to enrollment

• Known history of severe, immediate hypersensitivity reaction attributed to cyclophosphamide, fludarabine, dimethyl sulfoxide (DMSO), human serum albumin (HAS), phosphate buffer or gentamycin