Amtagvi (lifileucel) / Iovance Biotherap - LARVOL DELTA

Amtagiv for Advanced Melanoma Shows Strong Results in Real-World Use (Managed Healthcare Executive) - "A real-world study tracking the use of Amtagvi (lifileucel) in patients with advanced melanoma found nearly half saw their tumors shrink or disappear, matching the therapy’s effects in research settings and supporting its role as a new option after other treatments have failed. Among 41 patients with unresectable or metastatic melanoma, 49% experienced tumor shrinkage after receiving the first FDA-approved T cell therapy for solid tumors. Patients who had received fewer prior treatments responded even better: 61% of those who had tried two or fewer therapies before Amtagvi responded to treatment, compared with 33% among those with more heavily treated disease. The findings come from a retrospective study led by Amtagvi drugmaker Iovance Biotherapeutics and included a diverse group of patients previously treated with immune checkpoint inhibitors and targeted therapies."

Retrospective data • Melanoma

Lifileucel Therapy for Metastatic Melanoma: Advancements in Tumor-infiltrating Lymphocyte-based Immunotherapy. (PubMed, Anticancer Agents Med Chem) - "This breakthrough therapy not only addresses a critical unmet need in melanoma treatment but also represents a paradigm shift toward personalized medicine in oncology. Lifileucel underscores the potential of TILbased approaches to revolutionize cancer care, setting the stage for future advancements in immunotherapy."

Journal • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor

Engineered immune cell therapies for solid tumors: pharmacological advances, clinical outcomes, and future directions. (PubMed, Front Pharmacol) - "Clinically, TIL delivery has shown significant responses in advanced melanoma, with lifileucel gaining United States FDA approval as a pioneering TIL therapy for solid tumors...This review synthesizes recent advances in engineered immune cell therapies for solid tumors, emphasizing their pharmacological mechanisms, clinical efficacy, and translational potential. By addressing current hurdles, such as enhancing tumor penetration and minimizing adverse effects, this article outlines future directions to refine these therapies as safe, effective pharmacological tools in oncology."

Clinical data • Journal • Review • Melanoma • Oncology • Solid Tumor

Tumor-Infiltrating Lymphocyte Therapy for the Treatment of Metastatic Melanoma. (PubMed, Am J Clin Dermatol) - "Lifileucel was granted accelerated approval by the US Food and Drug Administration in February 2024 for the treatment of advanced melanoma, marking the first regulatory approval of a TIL product, and also the first approval of cellular therapy for the treatment of any solid tumor. Despite this landmark event, questions remain surrounding optimal TIL timing, sequencing with other treatment modalities, and the optimal TIL repertoire and phenotype. Innovations in cellular engineering are expected to improve the antitumor efficacy and safety profile of TIL therapy, advance our understanding of how best to deliver TIL therapy, and provide hope for paradigm-shifting approaches in the treatment of advanced melanoma as well as for other solid tumors."

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

Efficacy & Safety for LN144 With Pembrolizumab With High Risk Stage IIIb-dResectable Melanoma (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: James Isaacs, MD | N=12 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Melanoma • Oncology • Solid Tumor

Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study. (ASCO 2025) - P2 | "Before lifileucel infusion, pts underwent nonmyeloablative lymphodepletion (NMA-LD; cyclophosphamide, 60 mg/kg × 2 d plus fludarabine 25 mg/m2 × 5 d). This 5-year analysis of the C-144-01 trial is the longest follow-up of the largest group of pts with melanoma treated with tumor-infiltrating lymphocytes in a single study. This study illustrates lifileucel's continued durability of response and survival benefit up to 5 years after a single administration without any long-term safety concerns."

Clinical • IO biomarker • Metastases • Melanoma • Oncology • Solid Tumor

Outpatient treatment-related toxicity after hospital discharge among patients receiving lifileucel for advanced melanoma. (ASCO 2025) - "Rates of new severe toxicity and treatment-related readmissions were low among patients discharged post-lifileucel. About one in four patients required blood products after discharge. Identification of risk factors for the development of outpatient TRAEs may inform personalized care following lifileucel administration."

Clinical • Metastases • Melanoma • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • IL2

A phase Ib study to assess the safety and efficacy of autologous tumor infiltrating lymphocytes (lifileucel) with adjuvant pembrolizumab (PEMBRO) for treatment of immunotherapy naïve patients with high-risk clinical stage IIIb-d resectable melanoma (MEL). (ASCO 2025) - P1 | "Correlative studies include analysis of the phenotype, function and TCR repertoire of baseline TIL samples. Serial PBMC will be collected to monitor TIL persistence (based on TCR analysis) and functional activity."

Clinical • P1 data • Tumor-infiltrating lymphocyte • Melanoma • Oncology • Solid Tumor • IL2

Phase 2, multicenter study of frontline maintenance therapy with lifileucel plus pembrolizumab in advanced non-small cell lung cancer. (ASCO 2025) - P2 | "We added two new cohorts within this basket study, 3D and 3E, which evaluate if adding lifileucel to pembro ± pemetrexed in the maintenance phase of standard-of-care (SOC) therapy (from tumors procured in treatment-naive pts [3D] versus those who had already started receiving SOC chemotherapy [3E]) is feasible and provides added benefit with an acceptable safety profile...After completion of SOC chemotherapy, a dose of pembrolizumab will be given followed by nonmyeloablative lymphodepletion (NMA-LD) (day −5 to day −3: cyclophosphamide 20 mg/kg/day; day −5 to day −2: fludarabine 25 mg/m2/day)...Prior organ allograft or cell transfer therapy, symptomatic brain metastases, current systemic steroid therapy >10 mg/day of prednisone or other steroid equivalent, and active illnesses or autoimmune disorders are not permitted...Selected exploratory endpoints include in vivo T-cell persistence, correlative biomarkers, and circulating tumor DNA. Enrollment of..."

Clinical • IO biomarker • Metastases • P2 data • Immunology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • 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

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

Role of high-dose interleukin-2 for melanoma in the age of cellular therapy. (PubMed, J Immunother Cancer) - "In 2024, following decades of foundational work at the National Cancer Institute, lifileucel became the first FDA-approved tumor-infiltrating lymphocyte (TIL) therapy for cancer...Nevertheless, concerns related to HD IL-2 toxicity persist and possibly impact decisions to offer TIL when indicated. Here, we discuss the differences in the administration of HD IL-2 as a monotherapy vs an adjunctive therapy following TIL infusion, in an effort to demystify the toxicity of HD IL-2 in the era of cellular therapy."

Journal • Review • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Beyond Checkpoint Inhibition: Keeping Therapeutic Options Open. (PubMed, Am Soc Clin Oncol Educ Book) - "Combination immune checkpoint inhibitor therapy (ICI) with ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) + nivolumab (anti-PD-1) in untreated, metastatic melanoma has achieved a ten-year melanoma-specific survival of 52%...Addition of ipilimumab, relatlimab (anti-LAG3), or lenvatinib (VEGFR TKI) has minimal to modest efficacy...Recently, personalized, autologous tumor-infiltrating lymphocyte therapy has become a US Food and Drug Administration-approved second-line option; lifileucel demonstrates durable response (approximately 30%) in heavily pretreated, metastatic melanoma...As a therapy which is limited to patients who are HLA-A*02:01, T-cell receptor (TCR) engineered T cells (TCR-T) iterates on personalized adoptive cell transfer, and immune mobilizing monoclonal TCRs against cancer are CD3 bispecifics that bind glycoprotein 100 (tebentafusp, approved for metastatic uveal melanoma) or PRAME to activate T cells...ICI may be given with modified..."

Checkpoint inhibition • IO biomarker • Journal • Review • Eye Cancer • Immunology • Melanoma • Oncology • Solid Tumor • Transplantation • Uveal Melanoma • CTLA4 • HLA-A • NRAS • PRAME

Lifileucel: “The CHMP was updated on discussions at the CAT. The committee discussed the issues identified in this application”; Melanoma (European Medicines Agency) - CHMP Final Minutes of the meeting on 9- 12 Dec 2024: “The committee endorsed the recommendation and scientific discussion together with the list of questions, as adopted by CAT”

CHMP • Melanoma • Oncology

Additional details will be presented at ASCO (GlobeNewswire) - "Trial-in-Progress Poster: Phase 2, multicenter study of the lifileucel regimen and pembrolizumab after frontline platinum-doublet chemotherapy and pembrolizumab in advanced non-small cell lung cancer (Abstract TPS8659); Session: Lung Cancer-Non-Small Cell Metastatic, Saturday, May 31, 2025, 1:30 pm – 4:30 pm CDT."

Trial status • Non Small Cell Lung Cancer

Iovance Announces Five-year Results of Amtagvi (lifileucel) in Patients with Advanced Melanoma at ASCO Annual Meeting (GlobeNewswire) - P2 | N=178 | NCT02360579 | Sponsor: Iovance Biotherapeutics, Inc. | "The C-144-01 trial investigated Amtagvi in patients with advanced melanoma previously treated with anti-PD-1 and targeted therapy, where applicable....The long-term data are from 153 patients combined from cohorts 2 and 4 of the C-144-01 trial. With a median follow-up of 57.8 months, patients achieved a median OS of 13.9 months, with 19.7% of patients surviving at the five-year mark. The objective response rate was 31.4%, including complete responses in 5.9% of patients and partial response in 25.5%. Among patients who responded to treatments, the median duration of response was 36.5 months. Nearly a third of responders (31.3%) completed the five-year assessment with ongoing responses. Adverse events (AEs) were consistent with known safety profiles of nonmyeloablative lymphodepletion and interleukin-2 administration."

P2 data • Melanoma

Iovance Biotherapeutics Reports Financial Results and Corporate Updates for First Quarter 2025 (GlobeNewswire) - "1Q25 Amtagvi Revenue: Product revenue from U.S. Amtagvi sales was $43.6 million, impacted by a reduction in capacity during annual scheduled maintenance at the iCTC. Production has resumed enabling full capacity for infusions in the second quarter 2025....1Q25 Proleukin Revenue: Product revenue also included $5.7 million in Proleukin sales, primarily reflecting clinical and manufacturing use after stocking at major U.S. wholesalers in 2024. Significant orders are expected in the current quarter."

Sales • Melanoma • Renal Cell Carcinoma • Urothelial Cancer

Use of lenvatinib as bridging therapy for patients undergoing treatment with lifileucel: a single institution experience (EADO-WCM 2025) - "All three were primarily refractory to ipilimumab/nivolumab after progressing on prior adjuvant PD-1 therapy. Limited signal of efficacy was seen in three patients with primary resistance to combination ICI therapy. Updated data including additional patients will be presented."

Clinical • Cardiovascular • Gastrointestinal Disorder • Melanoma • Oncology • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • Solid Tumor

Iovance Biotherapeutics Reports Financial Results and Corporate Updates for First Quarter 2025 (GlobeNewswire) - "The IOV-LUN-202 trial is intended to support a potential accelerated approval of lifileucel in post-anti-PD-1 NSCLC in the U.S., with an anticipated regulatory decision in 2027....Iovance is actively enrolling in the IOV-END-201 Phase 2 trial for advanced endometrial cancer, with initial results expected in the second half of 2025."

FDA approval • P2 data • Non Small Cell Lung Cancer

Iovance Biotherapeutics Reports Financial Results and Corporate Updates for First Quarter 2025 (GlobeNewswire) - "2025 Regulatory Approvals for Amtagvi Expected in the UK, EU, and Canada....Named patient programs are planned outside the U.S. to provide early access to treatment prior to national reimbursement and are also expected to provide initial revenue from these markets. Additional regulatory submissions remain on track for Australia in the first half of 2025 and Switzerland in the second half of 2025."

Canada approval • EMA approval • Filing • MHRA approval • Melanoma

Iovance Biotherapeutics Reports Financial Results and Corporate Updates for First Quarter 2025 (GlobeNewswire) - "Iovance currently owns approximately 280 granted or allowed U.S. and international patents and patent rights for Amtagvi and other TIL-related technologies that are expected to provide exclusivity through at least 2042. This patent portfolio covers TIL compositions and methods of treatment and manufacturing in a broad range of cancers, with Gen 2 patent rights expected to provide exclusivity for Amtagvi into 2038 and additional patent rights, including methods of treating melanoma and compositions and methods for potency assays, expected to provide exclusivity into 2039 and 2042, respectively."

Patent • Melanoma

A Study of LN-144 or LN-145 in People With Advanced Uveal Melanoma, Undifferentiated Pleomorphic Sarcoma, or Dedifferentiated Liposarcoma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: May 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Eye Cancer • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • Uveal Melanoma

A Study to Investigate the Safety and Efficacy of IOV-3001 in Adults With Advanced Melanoma Who Will Receive Lifileucel (clinicaltrials.gov) - P1/2 | N=42 | Recruiting | Sponsor: Iovance Biotherapeutics, Inc.

New P1/2 trial • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor

Iovance Biotherapeutics Announces Participation in Upcoming Scientific Congresses (GlobeNewswire) - "Iovance Biotherapeutics...announced that pre-clinical data for IOV-5001, a genetically engineered, inducible, and tethered interleukin-12 (IL-12) TIL cell therapy, will be presented at the 2025 AACR Annual Meeting. In addition, five-year outcomes data from the C-144-01 study of lifileucel monotherapy in patients with advanced melanoma, and a poster on study design for lifileucel in frontline advanced non-small cell lung cancer, will be presented at the 2025 ASCO Annual Meeting."

Clinical protocol • P2 data • Preclinical • Melanoma • Non Small Cell Lung 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