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

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 • IL7R • MLH1

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])...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 therapies in patients. Disease Focus of Abstract:Cancer Hematologic"

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

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

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

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

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

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

E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Christian Hinrichs | Trial completion date: Jan 2025 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Anal Carcinoma • Cervical Adenocarcinoma • Cervical Cancer • Colorectal Cancer • Gene Therapies • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Vaginal Cancer • Vulvar Cancer • HLA-A

E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Christian Hinrichs | Not yet recruiting ➔ Recruiting

Enrollment open • Anal Carcinoma • Cervical Adenocarcinoma • Cervical Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Vaginal Cancer • Vulvar Cancer • HLA-A

Interleukin-2 and Pembrolizumab for Metastatic Kidney Cancer (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2025 ➔ Oct 2025

Trial completion date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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 | Recruiting ➔ Active, not recruiting | N=100 ➔ 56

Enrollment change • Enrollment closed • Colorectal Cancer • Oncology • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Solid Tumor

CIML NK Cells With Venetoclax for AML (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Active, not recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

To Evaluate the Safety and Efficacy of ADP-TILIL7 in Patients With Locally Advanced or Metastatic Melanoma (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Inge Marie Svane | Trial completion date: Apr 2027 ➔ Apr 2028 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Auto BMT for Non-M3 AML in 1st Remission in Pts </=60y of Age Using Busulfan/FTBI & VP16 as a Prep R (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ Aug 2025

Trial completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma (clinicaltrials.gov) - P3 | N=168 | Completed | Sponsor: The Netherlands Cancer Institute | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor

Therapy for Children With Advanced Stage Neuroblastoma (clinicaltrials.gov) - P2 | N=153 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • MYCN

A Phase 2 Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab (clinicaltrials.gov) - P2 | N=170 | Recruiting | Sponsor: National Cancer Institute (NCI) | N=20 ➔ 170 | Trial completion date: Jun 2026 ➔ Jun 2029 | Trial primary completion date: Jun 2025 ➔ Jun 2028 | Suspended ➔ Recruiting

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Entinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer (clinicaltrials.gov) - P1/2 | N=47 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2025 ➔ Feb 2026

Trial completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • mTOR

Iovance Biotherapeutics Reports Financial Results and Corporate Updates for Fourth Quarter and Full Year 2024 (GlobeNewswire) - "Iovance is reaffirming total product revenue guidance within the range of $450 to $475 million for 2025, the first full calendar year of Amtagvi sales...Revenue was $73.7 million for the fourth quarter of 2024 and consisted of product revenue from Amtagvi and Proleukin sales. Iovance recognized $48.7 million in revenue from Amtagvi infusions that were completed during the fourth quarter of 2024 and $25.0 million in global revenue for Proleukin...Revenue for the full year 2024 was $164.1 million and reflected product revenue of $103.6 million from Amtagvi and $60.5 million from Proleukin."

Commercial • Sales projection • Melanoma • Renal Cell Carcinoma • Urothelial Cancer

A Phase II Trial of Low-Dose Interleukin-2 (IL-2) Added to Extra-Corporeal Photopheresis for Steroid-Refractory cGVHD (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • IL2

HIRA to remove…drugs from Group 2 anticancer list, update reimbursement criteria (Korea Biomedical Review) - "The move, which is aimed at overhauling the reimbursement system and reflecting the latest clinical evidence, will take effect on March 1. The drugs that will be deleted from the list of Group 2 anticancer drugs are albumin-bound paclitaxel, aldesleukin(IL- 2), anagrelide, anastrozole, belotecan, capecitabine..."

Reimbursement • Oncology

TBio-4101 and Pembro wi/ or w/o Chemo in Recurrent/Metastatic HNSCC (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: May 2026 ➔ Aug 2026 | Trial primary completion date: May 2026 ➔ Aug 2026

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

Efficacy of Interleukin-2 in Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=10 | Not yet recruiting | Sponsor: Nova Scotia Health Authority | Trial completion date: Apr 2025 ➔ Apr 2028 | Trial primary completion date: Apr 2024 ➔ Apr 2028

Trial completion date • Trial primary completion date • Tumor mutational burden • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1