Amtagvi (lifileucel) / Iovance Biotherap - LARVOL DELTA

From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma. (PubMed, J Pers Med) - " TIL-based adoptive cell therapy is now a promising, personalized treatment for advanced melanoma after anti-PD-1 therapy has failed. Future studies should focus on identifying reliable biomarkers, improving TIL products, combining therapies to change the tumor environment, and making manufacturing more efficient to ensure more patients can safely access TIL therapy."

IO biomarker • Journal • Review • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • IL2

SUPRAME: A phase 3 trial comparing IMA203, an engineered T-cell receptor expressing T cell therapy (TCR-T) vs investigator's choice in patients with previously treated advanced cutaneous melanoma. (ASCO 2025) - P3 | "Following lymphodepletion with cyclophosphamide (500 mg/m2 x 4 days) and fludarabine (30 mg/m2 x 4 days), 1-10x109 IMA203 TCR-T cells will be administered, followed by low-dose IL-2 (1mio IU daily x5 days, twice daily x5 days). Patients in the control arm will receive approved investigator's choice of standard treatment (nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), chemotherapy)...Secondary endpoints include OS, ORR, safety and patient-reported outcomes (EORTC QLQ-C30, EQ-5D-5L). The trial will enroll patients in the US and Europe."

Clinical • IO biomarker • Metastases • P3 data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • HLA-A • PRAME

Infections after lifileucel tumor-infiltrating lymphocyte therapy for metastatic melanoma: a multi-centre study (ESCMID Global 2026) - No abstract available

Clinical • Metastases • Tumor-infiltrating lymphocyte • Infectious Disease • Melanoma • Oncology • Solid Tumor

Long-term Efficacy and Safety of Lifileucel Tumor-infiltrating Lymphocyte (TIL) Cell Therapy in Patients with Advanced Melanoma: A 5-year Analysis of the C-144-01 Study. (PubMed, J Clin Oncol) - "Most grade 3/4 cytopenias resolved to grade ≤ 2 by day 30. This 5-year analysis demonstrated long-term benefit and meaningful OS with one-time lifileucel therapy, with no additional long-term safety concerns."

Journal • Tumor-infiltrating lymphocyte • Hematological Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • Transplantation • IL2

SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma (clinicaltrials.gov) - P3 | N=360 | Not yet recruiting | Sponsor: Immatics US, Inc.

New P3 trial • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor • BRAF

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=48 ➔ 75

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=178 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | Trial completion date: Dec 2024 ➔ Aug 2029 | Trial primary completion date: Dec 2023 ➔ Aug 2029

Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=75 ➔ 135

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=36 ➔ 48

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=245 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=178 ➔ 245

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Iovance Biotherapeutics, Inc.

New P2 trial • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

IOV-COM-202: Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors (clinicaltrials.gov) - P2 | N=178 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc. | N=135 ➔ 178

Enrollment change • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: Immatics US, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor • BRAF

TUMOR-INFILTRATING LYMPHOCYTE CARDIOTOXICITY: A REAL-WORLD PHARMACOVIGILANCE STUDY OF FDA ADVERSE EVENT REPORTING SYSTEM (FAERS) (ACC 2026) - "Lifileucel based TIL-therapy is associated with an over 9-fold increase in reported CVAEs, and those who develop CVAEs appear to face higher mortality. Given the expected increase in TIL utilization, additional studies evaluating the mechanisms and prevention of this cardiotoxicity are needed."

Adverse events • Clinical • Real-world • Real-world evidence • Tumor-infiltrating lymphocyte • Cardiovascular • Melanoma • Oncology • Solid Tumor

Deep and durable response to tumor-infiltrating lymphocytes in a patient with SMARCA4-deficient lung cancer (DKK 2026) - "He received platinum-based curative-intent radiochemotherapy with subsequent durvalumab-maintenance. Our preliminary results suggest that TIL might be an efficacious treatment for SMARCA4 deficient lung cancer patients. Indication of source: 1. Alessi JV et al."

Clinical • IO biomarker • Tumor mutational burden • Tumor-infiltrating lymphocyte • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • SMARCA4 • TMB

SAME EVIDENCE, DIFFERENT DECISIONS: HOW REGULATORY STANDARDS SHAPE ORPHAN DRUG APPROVALS (ISPOR 2026) - "Three therapies with divergent outcomes were selected as case studies: palovarotene for Fibrodysplasia Ossificans Progressiva, lifileucel for advanced Melanoma, and arimoclomol for Neimann-Pick disease (type C). Variations in orphan drug regulatory outcomes reflect how regulators manage evidentiary and methodological uncertainty rather than differences in the underlying evidence. Aligning global evidence generation strategies with these regional standards is critical for mitigating pitfalls and enabling coordinated global approvals."

Frontotemporal Lobar Degeneration • Melanoma • Solid Tumor

Pipeline Updates (The Manila Times) - "New Data Across Several Pipeline Programs Anticipated Throughout 2026...The Phase 3 TILVANCE-301 trial of lifileucel and pembrolizumab in frontline advanced melanoma made significant progress, with enrollment accelerating across a broad and expanding global footprint...Two of Iovance’s Phase 2 trials, IOV-END-201 and IOV-MEL-202, are investigating lifileucel in previously treated patients with advanced endometrial cancer and melanoma, respectively...A Phase 1/2 trial is investigating IOV-4001...A Phase 1/2 trial is investigating IOV-3001...An Investigational New Drug (IND) submission is planned in the first half of 2026 to begin clinical development of IOV-5001, a genetically engineered, inducible, and tethered interleukin-12 TIL therapy, in a Phase 1/2 basket trial."

Clinical data • IND • New P1/2 trial • Trial status • Endometrial Cancer • Melanoma • Non Small Cell Lung Cancer • Ocular Melanoma • Oncology

Fourth Quarter and Full Year 2025 Financial Highlights (The Manila Times) - "Fourth quarter 2025 total product revenue of ~$87 million with strong growth of ~30% over the prior quarter, including: U.S. Amtagvi revenue of ~$65 million; Global Proleukin revenue of ~$22 million....Full year 2025 total product revenue of ~$264 million achieved the guidance range of $250 million to $300 million in the first full year of launch, including: U.S. Amtagvi revenue of ~$220 million; Global Proleukin revenue of ~$44 million."

Sales • Melanoma • Renal Cell Carcinoma

IOV-MEL-202: A study of lifileucel (tumor-infiltrating lymphocytes) in adults with advanced melanoma (clinicaltrialsregister.eu) - P1/2 | N=69 | Not yet recruiting | Sponsor: Iovance Biotherapeutics Inc.

New P1/2 trial • Melanoma • Oncology • Solid Tumor • BRAF

Strong U.S. Commercial Growth and Execution with Approvals Pending in New Global Markets (The Manila Times) - "A continuously growing and maturing network of U.S. authorized treatment centers (ATCs) expanded patient access in 2025, with further acceleration anticipated in 2026...Manufacturing turnaround improved to 32 days or less from inbound to return shipment to ATCs....Regulatory submissions are under review with potential approvals in the United Kingdom and Australia in the first half of 2026, and Switzerland in the first half of 2027; Iovance is working with the European Medicines Agency (EMA) to resubmit a marketing authorization application (MAA) in 2026."

Approval • Commercial • Filing • Melanoma

NCI-2021-11063: Neoadj Admin Autologous Tumor Infiltrating Lymphocytes & Pembrolizumab for Treatment of Adv Melanoma Patients (clinicaltrials.gov) - P1 | N=2 | Active, not recruiting | Sponsor: Richard Wu | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Tumor mutational burden • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Lifileucel in Previously Treated Advanced NSCLC: IOV-LUN-202 Registrational Trial (The Manila Times) - "Anticipated milestones: Present updated data at a major medical meeting in 2026; Complete enrollment in 2026; Support a supplemental Biologics License Application for U.S. accelerated approval with a potential launch in the second half of 2027."

Launch US • P2 data • Trial status • Non Small Cell Lung Cancer

Iovance Announces Positive Results from the First Clinical Trial for TIL Cell Therapy in Soft Tissue Sarcomas (The Manila Times) - "Among the first six evaluable patients treated with lifileucel monotherapy, physician-assessed confirmed ORR by RECIST v1.1 was 50%. All evaluable patients had advanced disease, were refractory to prior therapy, and had significant disease burden, with a mean sum of diameters of 117 millimeters at baseline and a mean of more than two prior lines of therapy....Based on these results, Iovance plans to commence a single arm registrational trial in second-line advanced UPS and DDLPS in the second quarter of 2026 and will engage with the U.S. Food and Drug Administration (FDA) on an accelerated path to expedite approval....'We look forward to presenting these results at a medical conference in 2026.'"

New trial • P1 data • Dedifferentiated Liposarcoma • Sarcoma • Undifferentiated Pleomorphic Sarcoma

Does tumor-infiltrating lymphocyte therapy improve survival outcomes in patients with advanced melanoma? (PubMed, Front Med (Lausanne)) - "With the 2024 FDA approval of Iifileucel (Amtagvi), a type of TIL therapy, this literature review aims to establish how effectively TIL therapy can treat metastatic and advanced melanomas, to evaluate if this type of therapy should be approved in the UK...Overall, the literature indicates that TIL therapy is a breakthrough drug that could change the treatment of melanoma, and allow patients another, effective treatment option, after first-line treatments are no longer suitable. This review concludes that future research should focus on larger cohort studies, and cost-effectiveness investigations to support approval in the UK."

Journal • Review • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Ovarian Cancer • Solid Tumor