Proleukin (aldesleukin) / Clinigen, Novartis, Iovance Biotherap - LARVOL DELTA

Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies (clinicaltrials.gov) - P1 | N=86 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2027 ➔ Sep 2031 | Trial primary completion date: Sep 2026 ➔ Sep 2031

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

SILVER: Adding IL-2 to Tebentafusp to Eradicate Cancer Progression (clinicaltrials.gov) - P1/2 | N=8 | Recruiting | Sponsor: St Vincent's Hospital, Sydney

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

[68Ga]Ga-interleukin-2 for imaging activated T-lymphocytes: biochemical characterization and phase I study in normal subjects. (PubMed, Eur J Nucl Med Mol Imaging) - "We developed an efficient lyophilized kit of THP-desIL2 for 68Ga-labelling at room temperature in GMP conditions, obtaining excellent in vitro and in vivo results. [68Ga]Ga-THP-desIL2 PET/CT studies in humans showed favorable dosimetry and safety, thus highlighting its potential for a wide range of clinical applications, particularly in immune-mediated diseases and cancer."

Journal • P1 data • Oncology • IL2

NCI-2018-00918: LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2025 ➔ Apr 2027 | Trial primary completion date: Jun 2025 ➔ Apr 2027

Platinum resistant • Trial completion date • Trial primary completion date • Breast Cancer • Carcinosarcoma • Endocrine Cancer • Giant Cell Tumor of Bone • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Osteosarcoma • Ovarian Cancer • Refractory Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • HER-2

TBio-4101 and Pembro wi/ or w/o Chemo in Recurrent/Metastatic HNSCC (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | N=15 ➔ 7 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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

Multiomic evaluation of TEV-56278, a PD-1-targeted attenuated IL-2 molecule, in a human ex vivo tumor model and association with immune activation with enhanced effector CD8 T cell selectivity. (ASCO 2025) - " PDTF from 15 renal cell carcinoma patients were treated ex vivo with TEV-56278 [100 µg/ml], aldesleukin [100 ng/ml, as positive control], or a control PD-1 non-targeted-AttIL-2 [100 µg/ml]. We performed in-depth characterization of TEV-56278 in a human tumor ex vivo system that incorporates features of the tumor microenvironment and models the dynamic response of TEV-56278. This study confirms that TEV-56278 targets IL-2 activity to PD-1 expressing T cells within the tumor microenvironment and induces strong immune response, thereby promoting anti-tumor activity. Understanding the mechanisms that drive variable responses in PDTF may improve precision immuno-oncology efforts and help optimize our clinical development strategy."

IO biomarker • Preclinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CCL20 • CD8 • CXCL10 • IL12A • IL2

EVICTION-2: Phase 1/2a Study of ICT01 Plus Low Dose SC IL-2 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=56 | Active, not recruiting | Sponsor: ImCheck Therapeutics | Trial primary completion date: Apr 2025 ➔ Sep 2025

Trial primary completion date • Colorectal Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Solid Tumor

STIL101 for Injection for the Treatment of Locally Advanced, Metastatic or Unresectable Pancreatic Cancer, Colorectal Cancer, Renal Cell Cancer, Cervical Cancer and Melanoma (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: City of Hope Medical Center | Initiation date: Apr 2025 ➔ Aug 2025

Trial initiation date • Cervical Cancer • Colorectal Cancer • Genito-urinary Cancer • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma • Solid Tumor

Biologics for the treatment of alopecia areata: A comprehensive review of clinical trials (SID 2025) - "Studies examining Dupilumab, Secukinumab, Tralokinumab, Abatacept, Alefacept, Efalizumab, and Aldesleukin were identified. Biologics offer a favorable safety profile and hold potential as therapeutic options for AA, although response rates remain inconsistent. Further research is needed to optimize these therapies, identify more effective targets, and determine predictors of clinical response."

Clinical • Review • Alopecia • Immunology • CTLA4 • IL12A • IL13 • IL2 • IL23A

Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer & High Dose IL-2 Metastatic Melanoma (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Apr 2025 ➔ Sep 2025

Trial completion date • Melanoma • Oncology • Solid Tumor

Prime Edited T-regulatory Cells for Immune Therapy (ASGCT 2025) - "Following gene transfer, Tregs were cultured in orthoIL2 (STK009; labeled "PE S100", 100 nM) or native IL-2 (Proleukin, 300 IU/ml; labeled "PE P300")...In conclusion, our data shows that PE is a promising approach for Treg engineering that should facilitate immune therapy without employing lentiviral vectors or generating DSBs. Disease Focus of Abstract:Inflammatory Disorders"

Gene Therapies • Graft versus Host Disease • Immunology • Inflammation • CD4 • FOXP3 • IL2 • IL7R

Leveraging Immuno-STAT stimulation via TCR and IL-2 signaling to specifically control CAR T cell expansion and persistence in vivo (ASGCT 2025) - P1 | "IL-2 signaling through a CAR-independent circuit uniquely eradicated solid tumor models [1], but the clinical utility of non-specific cytokine CAR-T support (e.g. IL2; aldesleukin) is limited by toxicity...The first clinical-stage Immuno-STAT, CUE-101, selectively activates and expands HPV-specific CD8+ T-cells and is associated with durable anti-tumor responses in HPV+ recurrent/metastatic head and neck cancers, with the objective response rate more than doubled in combination with pembrolizumab vs historic control of pembrolizumab alone (NCT03978689, [3])... We demonstrate that Immuno-STAT treatment together with engineering co-expression of cognate exogenous TCR can specifically control the expansion and persistence of CAR-T cells. Leveraging the clinical experience with CUE-101, we anticipate future evaluation of this approach to determine whether Immuno-STAT-controlled expansion of E.T.CAR-T can enhance and control expansion/persistence of adoptive cellular..."

CAR T-Cell Therapy • IO biomarker • Preclinical • Head and Neck Cancer • Hematological Malignancies • Oncology • Solid Tumor • CD8 • IL2

Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial. (PubMed, Lancet Oncol) - P1/2 | "These results support the safety and potential antitumour activity of inhibiting the immune checkpoint CISH through the administration of neoantigen-reactive CISH-knockout TILs, with implications for patients with advanced metastatic cancers refractory to checkpoint inhibitor immunotherapies, and provide the first evidence that a novel intracellular checkpoint can be targeted with therapeutic effect."

Journal • P1 data • Anorexia • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Infectious Disease • Microsatellite Instability • Oncology • Solid Tumor • Targeted Protein Degradation • MSI

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

Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI... (clinicaltrials.gov) - P2 | N=102 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Sep 2024 | Trial primary completion date: Jun 2025 ➔ Sep 2024

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

IDP-023 g-NK Cells Plus Ocrelizumab in Patients With Progressive Multiple Sclerosis (clinicaltrials.gov) - P1 | N=34 | Suspended | Sponsor: Indapta Therapeutics, INC. | Initiation date: Jan 2025 ➔ Jun 2026 | Recruiting ➔ Suspended

Trial initiation date • Trial suspension • CNS Disorders • Immunology • Multiple Sclerosis

Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma (clinicaltrials.gov) - P3 | N=1449 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Bone Marrow Transplantation • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • Transplantation

IOV-5001, autologous tumor-infiltrating lymphocytes (TIL) armored with inducible membrane-tethered IL-12, shows enhanced antitumor efficacy with an improved cellular state (AACR 2025) - "IOV-5001 demonstrated superior killing and effector cytokine production compared with unmodified TIL in a tumor antigen-directed TCR killing assay and against autologous tumor, irrespective of aldesleukin support. These findings demonstrate that IOV-5001 with inducible and membrane-tethered IL-12 confers superior antitumor activity compared with unmodified TIL. The enhanced molecular and functional characteristics highlight IOV-5001 as a promising product for enhancing TIL efficacy in solid tumors."

Clinical • IO biomarker • Tumor-infiltrating lymphocyte • Endometrial Cancer • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • IL10 • IL12A • IL5

A first-in-class αPD-1/αVEGF/IL-2v tri-specific fusion protein demonstrates promising anti-tumor efficacy in immune checkpoint inhibitor-resistant tumor models (AACR 2025) - "The αPD-1/αVEGF/IL-2v exhibited blocking activity against PD-1/PD-L1 binding comparable to pembrolizumab, showed VEGF/VEGFR blockade activity similar to that of αVEGF antibody, and effectively induced CD8+ T cell activation comparable to aldesleukin. The murine surrogate of αPD-1/αVEGF/IL-2v demonstrated dose-dependent anti-tumor efficacy, superior to αPD-1 or αPD-1/αVEGF bispecific antibody in both ICI-resistant MC38 and B16F10 tumor models without body weight loss. In conclusion, αPD-1/αVEGF/IL-2v represents a first-in-class tri-specific fusion protein with therapeutic potential to overcome the limitations of αPD-1 or αPD-1/αVEGF therapies."

Checkpoint inhibition • Preclinical • Trispecific • Oncology • CD8

Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma (clinicaltrials.gov) - P=N/A | N=19 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2025 ➔ Jan 2026

Trial completion date • Melanoma • Oncology • Solid Tumor

T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial primary completion date: Apr 2025 ➔ Oct 2025

Trial primary completion date • Gene Therapies • Lung Cancer • Oncology • Solid Tumor

A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies (clinicaltrials.gov) - P2 | N=65 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Tumor mutational burden • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Pancreatic Cancer • Small Intestinal Carcinoma • Solid Tumor

Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies (clinicaltrials.gov) - P1 | N=86 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology