Hiltonol (poly-ICLC) / Oncovir - LARVOL DELTA

ETAPA I: Peptide-based Tumor Associated Antigen Vaccine in GBM (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Mustafa Khasraw, MBChB, MD, FRCP, FRACP | Recruiting ➔ Active, not recruiting | N=36 ➔ 24

Enrollment change • Enrollment closed • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oncology • Solid Tumor • BIRC5 • MGMT

Characterization of a novel Leishmania antigen containing a repetitive domain and its potential use as a prophylactic and therapeutic vaccine. (PubMed, mSphere) - "An adjuvanted formulation of LinKAP with Poly ICLC, a polyinosinic-polycytidylic acid (Poly I:C) stabilized with carboxymethylcellulose and polylysine, was used to vaccinate mice and hamsters as a prophylactic vaccine for visceral leishmaniasis...This disease, caused by the Leishmania parasite, affects several populations globally and still lacks highly effective vaccines. Identifying LinKAP and its preliminary characterization also provides new perspectives for studying its role in the parasite's biology."

Journal • Infectious Disease • PLEC • TCHH

Evaluation of tumor associated P30-peptide antigen (ETAPA): Safety and immunogenicity in a phase 1b trial in glioblastoma (AACR 2025) - P1 | "Administered with poly-ICLC as an adjuvant, this vaccine induces inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 to enhance antigen presentation and CD8+ T-cell activation, while the tetanus toxoid-derived P30 peptide serves as a helper epitope to amplify CD4+ T-cell responses and boost overall immunogenicity...Patients receive seven doses of the vaccine following standard radiation therapy and concomitant temozolomide treatment, with an escalating peptide dose...Furthermore, patients which developed vaccine specific immunity had higher baseline B cell percentages. Comprehensive data from flow cytometry and scRNA VDJ TCR sequencing of B and T cell receptors in PBMCs, collected both pre- and post-vaccination will be presented, this data will inform subsequent steps in clinical development."

Clinical • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • IFNG • IL6 • TNFA

Low-intensity pulsed focused ultrasound, with microbubbles and immune adjuvants, promotes CNS epitope spreading, improving CAR T cell therapy for heterogeneous brain tumors (AACR 2025) - "Therapeutic efficacy was associated with the presence of endogenous immune cells targeting other tumor antigens within the CNS. Collectively, our findings suggest that LIPU/MB, in combination with poly-ICLC and Interleukin-2, can overcome the inherent limitations of CAR T cell therapy by promoting CNS antigen presentation to the peripheral immune system inducing endogenous tumor-tumor-specific immune responses that enhance the efficacy of CAR T cell therapy."

CAR T-Cell Therapy • Clinical • Heterogeneity • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oncology • Solid Tumor • B2M • IL2

KRAS-Targeted Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Cancer (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2027 ➔ Nov 2028 | Trial primary completion date: Nov 2027 ➔ Nov 2028

Trial completion date • Trial primary completion date • Colorectal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Mutant CALR-peptide Based Vaccine in Patients With Mutated CALR Myeloproliferative Neoplasm (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Marina Kremyanskaya | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Essential Thrombocythemia • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • CALR

Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Feb 2025 ➔ May 2025

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

In Vitro and In Vivo Immunogenicity of a Dendritic Cell-Based Vaccine Targeting HBV Epitopes (CROI 2025) - "The immunogenicity of the resulting CD40.HBV vaccines was evaluated in hCD40 transgenic mice in a prime/boost regimen (10mcg/mouse with 50mcg of Poly-ICLC)...Conclusions Two CD40-targeting vaccine candidates, incorporating 6 highly immunogenic HBV peptides, were produced with high quality and demonstrated immunogenicity in vivo, and were able to recall memory T-cell responses from PBMCs of NUC-treated CHB patients. These vaccines are promising candidates for further testing in humanized mice and for assessing their therapeutic potential."

Preclinical • Hepatitis B • Infectious Disease • CD8 • IFNG • IL2

NF111: A Phase II Trial of Poly-ICLC for Low-Grade Gliomas (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: University of Alabama at Birmingham | N=20 ➔ 3 | Trial completion date: Feb 2027 ➔ Nov 2024 | Recruiting ➔ Terminated; The closure of the study is due to the lack of enrollment and the lack of evaluable patients.

Enrollment change • Trial completion date • Trial termination • Brain Cancer • CNS Tumor • Genetic Disorders • Glioma • Neurofibromatosis • Oncology • Solid Tumor • NF1

Unadjuvanted CD40.HIVRI.ENV Vaccine Late Boost Induces Durable Immune Responses: ANRS/VRI06 Trial (CROI 2025) - P1 | "The ANRS/VRI06 phase I trial (NCT04842682) enrolled 72 non HIV-infected volunteers to receive either 0·3, 1·0, or 3·0 mg of CD40.HIVRI.Env (TLR3-Hiltonol® adjuvanted) alone or co-administered with DNA-HIV-PT123 at weeks (W) 0, 4 and 24, randomized 5:1 active vs. placebo. A single late boost of CD40.HIVRI.Env, even unadjuvanted, was sufficient to maintain humoral and cellular long-term responses. These results reveal the potency of CD40-DC targeting vaccines to induce durable responses."

Clinical • Infectious Disease • CD40 • IFNG • IL2 • TLR3

Personalized Cancer Vaccine (PCV) Strategy in Patients with Solid Tumors and Molecular Residual Disease (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | N=75 ➔ 12

Enrollment change • IO biomarker • Trial completion • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B • PD-L1

Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Peptide-Pulsed Dendritic Cell Vaccination in Combination With Nivolumab and Ipilimumab for the Treatment of Recurrent and/or Progressive Diffuse Hemispheric Glioma, H3 G34-mutant (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Jonsson Comprehensive Cancer Center | N=15 ➔ 0 | Trial completion date: May 2030 ➔ Dec 2030 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial completion date • Trial withdrawal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer. (PubMed, Clin Cancer Res) - P1 | "Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity. Pre-existing rather than treatment-induced immune activation was associated with clinical benefit across cohorts, highlighting the importance of baseline immune fitness."

Journal • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TNFA

Clinical and Translational Results from PORTER, a Multi-cohort Phase 1 Platform Trial of Combination Immunotherapy in Metastatic Castration-Resistant Prostate Cancer (Clin Cancer Res) - P1 | N=43 | PORTER (NCT03835533) | "43 patients enrolled (N = 14, 15, 14 in Cohorts A, B, C). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 10 (71%), 2 (13%), and 2 (14%) patients, respectively, with one Grade 5 TRAE in Cohort A. Composite response rates were 7% (1/14), 33% (5/15), and 7% (1/14). Across cohorts, 6-month disease control was associated with pre-existing memory/regulatory T cells, TNFα, and other inflammatory pathways....Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity."

P1 data • Castration-Resistant Prostate Cancer

Comparing Neoadjuvant/Adjuvant GVAX vs a mKRASvax Given With Anti-PD-1 and Anti-CD137 for Surgically Resectable Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=38 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

IO biomarker • New P1/2 trial • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD20

Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: May 2033 ➔ Aug 2033 | Initiation date: Nov 2024 ➔ Feb 2025 | Trial primary completion date: Jun 2028 ➔ Sep 2028

Trial completion date • Trial initiation date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A Vaccine Trial for Low Grade Gliomas (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: James Felker | Trial primary completion date: Dec 2024 ➔ Jan 2026 | Trial completion date: Aug 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

1B-22-2: In Situ Immunomodulation with CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients W/ Unresectable and Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: University of Southern California | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Immunomodulating • Metastases • Trial completion date • Trial primary completion date • Basal Cell Carcinoma • Breast Cancer • HER2 Breast Cancer • Immunology • Melanoma • Merkel Cell Carcinoma • Oncology • Osteosarcoma • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • HER-2

NCI-2018-01581: Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Nov 2025 | Trial primary completion date: Dec 2024 ➔ Nov 2025

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • ER • HER-2 • PD-L1 • PGR

Safety and immunogenicity of CD40.HIVRI.Env, a dendritic cell-based HIV vaccine, in healthy HIV-uninfected adults: a first-in-human randomized, placebo-controlled, dose-escalation study (ANRS VRI06). (PubMed, EClinicalMedicine) - P1 | "Volunteers were randomized (5:1 active versus placebo) in groups receiving either 0.3, 1.0, or 3.0 mg CD40.HIVRI.Env (Hiltonol® adjuvanted) alone or co-administered with DNA-HIV-PT123 at weeks (W) 0, 4, and 24. CD40 targeting Env-based vaccines may be instrumental for inducing protective vaccine responses in prime-boost strategies. ANRS Emerging infectious diseases (ANRS MIE); Vaccine Research Institute (VRI)."

Journal • P1 data • Human Immunodeficiency Virus • Infectious Disease • CD40 • IFNG • IL2

A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2024 ➔ Jun 2024

Enrollment open • Trial initiation date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

A Pilot Study of Glioma Associated Antigen Vaccines in Conjunction with Poly-ICLC in Pediatric Gliomas (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: James Felker | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Nov 2024

Trial completion • Trial completion date • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oligodendroglioma • Oncology • Pediatrics • Solid Tumor

Preliminary results of a multicentric randomized phase I/IIa trial of an immunotherapy targeting dendritic cells (DC), CD40HVac, in patients with HPV16-positive oropharyngeal carcinoma (OPC) (ESMO-IO 2024) - P1/2 | "Twelve pts were included per dose group (1 (completed), or 3 mg (ongoing) CD40HVac subcutaneously-adjuvanted with Hiltonol®1mg), and randomized 5:1 to receive vaccine or placebo at Week (W) 0, 4 and 24 starting 16 – 22 W after end of curative treatment. AIM assay confirmed the elicitation of HPV-specific CD4+ and CD8+ T cells.Conclusions Adjuvanted CD40HVac immunotherapy is well tolerated in OPC HPV16-positive pts and induced, after two boosts at the lowest dose, specific and functional T-cell responses including CD8+ T cells exhibiting markers of cytotoxicity. W26 immunogenicity results will be presented."

Clinical • IO biomarker • P1/2 data • Oncology • Oropharyngeal Cancer • Solid Tumor • CD40 • CD8 • GZMB • IFNG • IL2 • LAMP1