A Phase I Trial of Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes and ANV419 in Patients With Advanced Melanoma. The BaseTIL-03M Trial
Overview
- Phase
- Phase 1
- Intervention
- Combination of Tumor-infiltrating lymphocyte transfer with ANV419
- Conditions
- Advanced Melanoma
- Sponsor
- University Hospital, Basel, Switzerland
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events (%)
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
In this study we aim to investigate safety and tolerability of tumor-infiltrating lymphocytes (TIL) adoptive cell therapy (ACT) incorporation in-vivo TIL expansion with ANV419 in patients with advanced melanoma
Detailed Description
In brief, this trial consists of four study periods: screening, pre-treatment, treatment, and observational follow-up. In the screening period, patients are screened for trial eligibility. In the pre-treatment period, patients have excisional biopsy/surgical resection of tumor lesion(s) (tumor collection) and TILs are expanded from this lesion/these lesions (TIL expansion). Patients are permitted to receive bridging therapy outside of the study protocol. In the treatment period, patients have TIL-ACT. TIL-ACT includes a detailed procedure of preparative chemotherapy, followed by transfer of the TIL product, followed by in-vivo TIL expansion with ANV419 (2 doses). TIL transfer is defined as day 0 in the study protocol. Patients have an End of Treatment visit (14 days after the last study treatment), a safety follow-up (30 days after the last study treatment) and an efficacy follow up, which is the End of Study visit (day +90). Thereafter, patients will transfer to observational follow-up, which is conducted every 3 months until 1 year after TIL transfer. Patients who terminate the study prematurely during any of the treatment period due to e.g., disease progression, toxicity, patient wish, etc. will also transfer to observational follow-up. The regimen (TIL-ACT with ANV419) has not been tested. Review by the IDSMB (independent data safety monitoring board) will be performed after 3 patients (safety check).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients who meet all the following criteria will be eligible to participate in the study:
- •Must provide written informed consent for the study.
- •Must be able to comply with the study protocol as judged by the investigator.
- •Are ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Have pathologically confirmed stage III (unresectable) or stage IV (metastatic) cutaneous melanoma, as per the American Joint Committee on Cancer staging system, 8th edition, and have experienced disease progression and exhausted all approved treatment option with curative intent.
- •Have received at least one prior systemic treatment line of PD-(L)1 inhibitor and BRAF/MEK inhibition in case of BRAFV600 mutated melanoma. Adjuvant systemic treatment terminated ≥12 months prior to diagnosis of metastatic disease is not counted as a treatment line.
- •Accessible tumor lesion(s) for TIL collection and willingness of the patient to undergo biopsy/resection of tumor lesion(s).
- •Measurable disease as per RECIST v1.1 (following biopsy/resection of tumor lesion(s) for TIL collection).
- •Adequate organ function (pulmonary, cardiovascular, hematological, hepatic, and renal function) per investigator's judgment. Cardiac stress testing is mandatory for all patients with underlying cardiac conditions and patients with age ≥50 years.
Exclusion Criteria
- •LDH (lactate dehydrogenase) ≥ 2x upper limit of normal (ULN).
- •Life-expectancy ≤ 3 months per investigator's judgment.
- •Have not recovered (i.e., ≤ Grade 1 or at baseline with the exception of alopecia or fatigue \[up to Grade 2 allowed\]) from immune-related adverse events (irAEs) resulting from prior immunotherapies. Patients who have endocrine immune-related AEs controlled by replacement therapy (i.e., hypothyroidism) due to previous treatment are eligible provided replacement therapy has been initiated and toxicity has returned to Grade
- •Have not recovered (i.e., ≤ Grade 1 or at baseline) from toxicities due to a previously administered chemotherapy, targeted small molecule therapy, or radiation therapy.
- •Note: If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study drug. Major surgery is defined as any surgery requiring entrance into a body cavity (e.g., chest, abdomen, or brain), organ removal, normal anatomy alteration, or joint replacement. Minor surgery is defined as any surgery in which skin, mucosa, or connective tissue sections are altered (e.g., biopsy, cataract, endoscopic procedures, etc.).
- •Have been diagnosed with uveal/ocular or mucosal melanoma.
- •Have a known additional malignancy (including all in-situ carcinoma) that is progressing or required active treatment within 2 years prior to enrollment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have undergone potentially curative therapy and have no evidence of disease or in situ cervical cancer in patients who completed cancer-directed therapy or have evidence of stable disease and do not require active treatment.
- •Have active central nervous system metastases and/or carcinomatous meningitis regardless of clinical stability. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to study treatment (day -7 in the study protocol), and any neurologic symptom has returned to baseline. New or enlarging brain metastases, as well as the use of steroids (≥10 mg of prednisone daily or equivalent) within the last 7 days prior to study drug are excluded.
- •Have a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study treatment (day -7 in the study protocol).
- •Are receiving systemic steroid ≥10 mg of prednisone daily or equivalent for any reason. Local steroid therapies (e.g., otic, ophthalmic, intra-articular, or inhaled medications) are acceptable. -
Arms & Interventions
Tumor-infiltrating lymphocyte transfer combined with ANV419
Patients have excisional biopsy/surgical resection of tumor lesion(s) (tumor collection) and TILs are expanded from this lesion/these lesions (TIL expansion). The transplant product will be produced in the Good Manufacturing Practice (GMP) facility of the University Hospital in Basel. TIL transfer to patient and first administration of ANV419 at day 0.
Intervention: Combination of Tumor-infiltrating lymphocyte transfer with ANV419
Outcomes
Primary Outcomes
Incidence of adverse events (%)
Time Frame: up to one year after TIL transfer
Incidence of adverse events (%) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with ANV419
Frequency of adverse events (number)
Time Frame: up to one year after TIL transfer
Frequency of adverse events (number) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with ANV419
Severity of adverse events (CTCAE v5.0 criteria)
Time Frame: up to one year after TIL transfer
Severity of adverse events (CTCAE v5.0 criteria) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with ANV419. CTCAE (Common Terminology Criteria for Adverse Events): Grade 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal.
Secondary Outcomes
- Progression-fee Survival (PFS)(up to one year after TIL transfer)
- Objective Response Rate (ORR)(up to one year after TIL transfer)
- Duration of response (DOR)(up to one year after TIL transfer)
- Overall survival (OS)(up to one year after TIL transfer)