Clinical trial NCT05397093: ITIL-306 in Advanced Solid Tumors
Official title: A Phase 1a/1b, Open-Label, Multicenter Study Evaluating the Safety and Feasibility of ITIL-306 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Epithelial Ovarian Cancer
Non-small Cell Lung Cancer
Renal Cell Carcinoma
Keywords: ITIL-306
Cell Therapy
Epithelial ovarian cancer (EOC)
Non-small cell lung cancer (NSCLC)
Renal cell carcinoma (RCC)
Fallopian tube carcinoma
Tumor Infiltrating Lymphocytes
TIL
T-cell therapy
Folate receptor α (FOLR1)
Anti-folate receptor α (FOLR1)
Autologous Adoptive Cell Therapy
Checkpoint, PD-1 axis inhibitor
Peritoneal carcinoma
Cellular Immunotherapy
Immuno-oncology
Costimulatory antigen receptor (CoStAR)
Lead sponsor: Instil Bio
Sponsor class: INDUSTRY
First posted: 2022-05-31
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Frequency and severity of ITIL-306 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (AESI)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 60 months
measure: Duration of response (DOR)
timeFrame: Up to 60 months
measure: Progression-free survival (PFS)
timeFrame: Up to 60 months
measure: Overall Survival (OS)
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Instil Bio, Inc.
name: Instil Study Director
role: STUDY_DIRECTOR
References: