Advanced Cutaneous Melanoma
Conditions
Keywords
ITIL-168, Cell Therapy, melanoma, Autologous cell therapy, Cellular Immunotherapy, TIL, Autologous Adoptive Cell Transfer, Immuno-oncology, IL-2, Autologous Adoptive Cell Therapy, Tumor Infiltrating Lymphocytes, T-cell therapy
Brief summary
DELTA-1 is a phase 2 clinical trial to evaluate the efficacy and safety of ITIL-168 in adult subjects with advanced melanoma who have previously been treated with a PD-1 inhibitor. 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 patient's own TILs. A tumor sample is removed from each patient to make a personalized ITIL-168 product. Once ITIL-168 has been made, the patient is treated with 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.
Sponsors
Instil Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All enrolled participants are assigned to be treated with a single dose of ITIL-168
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically confirmed advanced (unresectable or metastatic) cutaneous melanoma. * Cohort 1: Disease that is relapsed after or refractory to at least 1 prior line of systemic therapy that must include a PD-1 inhibitor and, if positive for proto- oncogene BRAF V600 activating mutation, targeted therapy. * Cohort 2: Disease that is persistent after discontinuing PD-1 due to toxicity. Patients with a proto-oncogene BRAF V600 activating mutation must have progressed after targeted therapy. * Cohort 3: Disease that is stable (SD) after at least 4 doses of a PD-1 inhibitor. Patients with a proto-oncogene BRAF V600 activating mutation must have progressed after targeted therapy. * 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 * Melanoma of uveal, acral, or mucosal origin * 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, or IL-2.
Design outcomes
Primary
| 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 central review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| ORR as determined by investigators | Up to 60 months | ORR as determined by investigators is defined as the incidence of a CR or a PR per a modified RECIST v1.1, as determined by study investigators. |
| Duration of Response | Up to 60 months | For subjects who experience an objective response, duration of response (DOR) is defined as the time from their first objective response to disease progression or death. |
| Disease Control Rate | Up to 60 months | Disease control rate (DCR), defined as the incidence of CR, PR, or stable disease (SD) per a modified RECIST v1.1 criteria, as determined by central review. |
| Best Overall Response | Up to 60 months | — |
| Time to Response | Up to 60 months | — |
| Frequency, duration, and severity of ITIL-168 treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest | Up to 60 months | — |
Countries
Canada, United Kingdom, United States
Outcome results
None listed