OncoMatch/Clinical Trials/NCT06630611
Evaluation of a Pragmatic Approach to Adoptive Cell Therapy (ACT) Using an IL2 Analog (ANV419) vs High Dose IL2 After Tumor Infiltrating Lymphocytes (TIL) Therapy in Patients With Melanoma, NSCLC and Cervical Cancer (PragmaTIL)
Is NCT06630611 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including NMA-LD regimen and Tumor infiltrating lymphocytes adoptive cell therapy (TIL-ACT) infusion for melanoma.
Treatment: NMA-LD regimen · Tumor infiltrating lymphocytes adoptive cell therapy (TIL-ACT) infusion · High dose IL-2 · IL-2 analog — Background: The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity. TIL-based ACT (Adoptive cell therapy using tumor-infiltrating lymphocytes product) is a modality of ACT used to treat patients with multiple types of cancer and it consists in the adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes obtained from tumor resection or tumor biopsies in patients following a non-myeloablative lymphodepleting (NMA-LD) chemotherapy. Ex vivo expansion of TIL relies on the non-specific expansion of lymphocytes present in tumor single cell suspensions or tumor fragments in high dose IL-2. Although proven efficacy in selected, the HD-IL-2 use remains relatively restricted due to toxicity. Due to the short serum half-life and the need to achieve an immune-modulatory effect in the tissues, IL-2 must be given in doses that induce severe systemic toxicities, including capillary leak syndrome (CLS), pulmonary edema, hypotension, acute renal insufficiency, and rarely myocarditis, limiting its applicability in cancer. Studies comparing HD-IL-2 with lower doses both in renal cell carcinoma and metastatic melanoma to minimize toxicity demonstrated the superiority of the high dose regimens in both diseases. These drawbacks of HD-IL-2 use encouraged the development of improved IL-2-based biologic agents with higher selectivity for effector immune cell subsets, reduced toxicity, and prolonged half-life. ANV419 is a novel IL-2 agent, which has been developed as a preferentially IL-2Rβγ directed fusion protein with a longer half-life. It has shown high effector selectivity and a favorable safety profile in preclinical testing, including in nonhuman primates, and it has been investigated in an ongoing open-label, dose-escalation Phase I Study in multiple tumor types. he safety profile of ANV419 is characterized by pyrexia, nausea, vomiting, ALT/AST changes and CRS in some patients. Most events are low grade and self-limiting and manageable with standard supportive care. ANV419 was well-tolerated by most patients. No patient discontinued treatment due to treatment related AE. Taking all the previous information into account, the primary objectives of this study are: 1. To determine whether TIL-ACT using the IL-2 analog ANV419 reduces the mean number of predefined grade ≥3 relevant adverse events related to interleukin use (based on Common Terminology Criteria for Adverse Events v5.0 - CTCAE v5.0) compared to TIL-ACT using HD-IL-2. 2. To determine whether TIL-ACT using the IL-2 analog improves patient´s reported outcomes (PRO) compared to TIL-ACT using HD-IL-2
Check if I qualifyExtracted eligibility criteria
Cancer type
Melanoma
Small Cell Lung Cancer
Cervical Cancer
Disease stage
Metastatic disease required
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Must have received: systemic anticancer therapy — adjuvant or metastatic
disease must have progressed to at least one standard systemic anticancer therapy, regardless whether in the adjuvant or metastatic setting, or the patient is unable/unwilling to receive standard therapy
Cannot have received: anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy
Exception: palliative radiotherapy for bone metastasis >2 weeks before preparative lymphodepleting therapy, denosumab, bisphosphonates, androgen-deprivation therapy for prostate cancer and hormonal therapy for breast cancer
Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy
Cannot have received: non-cytotoxic drug and molecular targeted therapy
Patients who have received any non-cytotoxic drug and molecular targeted therapy within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter)
Cannot have received: investigational agent
Patients who have received any investigational agent within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter)
Cannot have received: investigational cell or gene therapies
Patients who have previously received any investigational cell or gene therapies
Lab requirements
Blood counts
haemoglobin ≥9.0 g/dL; ANC ≥1.5x10E9/L without filgrastim; platelets ≥100x10E9/L; PT and aPTT ≤1.5 x ULN (unless on therapeutic anticoagulation)
Kidney function
serum creatinine <1.5 mg/dL or creatinine clearance ≥50 ml/min (Cockcroft-Gault)
Liver function
AST or ALT ≤3 x ULN (≤5 x ULN with liver metastases); total bilirubin <2 mg/dL (≤3 mg/dL with Gilbert's Syndrome)
Cardiac function
LVEF ≥45%
adequate hematological, renal, and hepatic functions defined by: Haemoglobin ≥9.0 g/dL. An absolute neutrophil count ≥ 1.5x10E9/L without the support of filgrastim. Platelets ≥100x10E9/L. PT and aPTT ≤1.5 x ULN (unless receiving therapeutic anticoagulation). AST or ALT ≤3 x ULN. Patients with liver metastases must have AST and ALT ≤5.0 x ULN. Total bilirubin <2 mg/dL. Patients with Gilbert's Syndrome must have a total bilirubin ≤3.0 mg/dL. Serum creatinine <1.5 mg/dL or measured creatinine clearance ≥50 ml/min calculated using the Cockcroft-Gault glomerular filtration rate estimation. Patients with documented LVEF of ≥ 45%.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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