Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Non-small Cell Lung Cancer
Conditions
Keywords
ITIl-168, Cell Therapy, Cervical cancer, Head and neck squamous-cell carcinoma (HNSCC), Non-small cell lung cancer (NSCLC), Autologous Adoptive Cell Therapy, Cellular Immunotherapy, Immuno-oncology, Tumor Infiltrating Lymphocytes, TIL, T-cell therapy, IL-2, pembrolizumab, Checkpoint inhibitor (CPI), PD-1 pathway inhibitors
Brief summary
DELTA-2 is a phase 1 clinical trial to evaluate the safety, feasibility, and preliminary efficacy of ITIL-168 with pembrolizumab in participants with advanced cancer whose disease has progressed after standard therapy. ITIL-168 is a cell therapy derived from a patient's own tumor-infiltrating immune cells (lymphocytes; TILs).
Interventions
BIOLOGICALITIL-168
ITIL-168 is a cell therapy product derived from a participant's own TILs. A portion of tumor is resected to make a personalized ITIL-168 product. If appropriate, participants may receive bridging therapy after recovering from the tumor resection during ITIL-168 manufacturing. Once ITIL-168 has been made, the participant is treated with up to 5 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by a single infusion of ITIL-168, and up to 8 doses of IL-2. Drug: Pembrolizumab Participants will receive 1 dose of pembrolizumab following tumor resection prior to receiving ITIL-168, and additional doses for up to a year after ITIL-168 infusion.
Sponsors
Instil Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically documented advanced (metastatic and/or unresectable) cervical cancer, HNSCC, or NSCLC. * Cohort 1: Participants with cervical cancer whose disease progressed during or after at least 1 prior line of chemotherapy. * Cohort 2: Participants with HNSCC whose disease progressed during or after chemotherapy that must have included a platinum agent and previous CPI. * Cohort 3: Participants with NSCLC whose disease progressed during or after 1 prior line of platinum-based chemotherapy and a CPI. Participants with targetable mutations (e.g. EGFR/ALK) are required to have progressed on targeted therapy and platinum-based chemotherapy * 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 * Neuroendocrine carcinoma, nasopharyngeal carcinoma, squamous cell carcinoma of the lip, or histopathology with neuroendocrine differentiation * 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, IL-2, of CPI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and severity of ITIL-168 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest | Up to 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | Up to 60 months | Objective response rate (ORR), defined as the incidence of a complete response (CR) or a partial response (PR) per a modified Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria, as assessed by investigator review. |
| Duration of response | Up to 60 months | For participants who experience an objective response, duration of response (DOR) is defined as the time from their first objective response to disease progression or death. |
| Progression-free Survival | Up to 60 months | Progression-free survival (PFS) is defined as the time from the ITIL-168 infusion date to the date of disease progression or death from any cause. |
| Overall Survival | Up to 60 months | Overall survival (OS) is defined as the time from the ITIL-168 infusion date to the date of death from any cause. |
Outcome results
None listed