Hiltonol (poly-ICLC) / Oncovir - LARVOL DELTA

Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in HVTN 706 (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: May 2027 ➔ Nov 2027 | Trial primary completion date: Jul 2026 ➔ Nov 2027

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Prophylactic peptide vaccine targeting resistance mutations in advanced ALK-positive lung cancer: Primary analysis from the ARCHER trial. (ASCO 2026) - P1/2 | "Patients continued their ALK TKI and received ALK-Vac, consisting of synthetic long peptides targeting seven common ALK resistance mutations (I1171T, I1171N, I1171S, L1196M, G1202R, D1203N, E1210K) plus poly-ICLC adjuvant...Concomitant TKIs included alectinib (7/15, 47%), lorlatinib (5/15, 33%), and brigatinib (3/15, 20%)... ALK-Vac was well-tolerated and induced vaccine-specific T cell responses in a minimal residual disease setting, demonstrating feasibility of prophylactic targeting of ALK resistance mutations as an adjunct to TKI therapy and supporting a broader immune-interception framework potentially applicable to other oncogene-driven NSCLC. Comprehensive cfDNA and immune-phenotyping analyses will be reported."

First-in-human • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • IFNG • KRAS

A phase 1 study of in situ Immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC ± pembrolizumab and tocilizumab – Safety and preliminary antitumor activity in patients with unresectable and metastatic solid tumors (ESMO 2026) - No abstract available

Clinical • Immunomodulating • Metastases • P1 data • Oncology • Solid Tumor

A therapeutic vaccine for fibrolamellar hepatocellular carcinoma. (ASCO 2025) - P1 | "The primary objectives were safety and T cell responses, defined as 2.5-fold increase of interferon gamma (IFN-γ)-producing DNAJB1-PRKACA chimera-specific T cells in the peripheral blood after week 10 (priming phase)...FLC-Vac, consisting of a peptide encoding the DNAJB1-PRACA fusion plus poly-ICLC adjuvant, was administered on weeks 0, 1, 2, 3, 6, 9 during the priming phase of the study. Nivolumab, 3 mg/kg, followed by ipilimumab, 1 mg/kg, was administered every 3 weeks for 4 doses during the priming phase... Our findings demonstrate the potential for therapeutic vaccines targeting DNAJ-PKAc in FLC and suggest a rubric for evaluating effective anti-neoantigen immunity."

Hepatocellular Cancer • Oncology • Solid Tumor • DNAJB1 • IFNG • PRKACA

PD-1 blockade following DC vaccination, compared with before vaccination, enhances T cell responses and extends survival in patients with recurrent GBM (EANO 2026) - P1 | "To extend this into patients, we conducted an investigator-sponsored, surgical window-of-opportunity trial (NCT04201873) in 46 patients with relapsed, resectable glioblastoma.Material and Participants were randomized to receive either neoadjuvant + adjuvant PD-1 mAb blockade (pembrolizumab, 400 mg IV q 6 weeks) together with adjuvant autologous tumor lysate-pulsed dendritic cell vaccination (ATL-DC, 1x106 DC + 20 ug/kg poly ICLC; Arm A), or a placebo IV infusion before resection followed by adjuvant ATL-DC/poly ICLC (Arm B). ATL-DC vaccination followed by PD-1 mAb blockade results in enhanced anti-tumor T cell responses and statistically significant survival compared with PD-1 mAb blockade given before surgical resection and concomitant with ATL-DC. As such, the order of administration of vaccine and ICB may be important."

Clinical • IO biomarker • Tumor mutational burden • Glioblastoma • Oncology • GZMB • TMB

Mutant KRAS peptide-based vaccine in patients at high risk of developing pancreatic cancer: Preliminary analysis from a phase I study (AACR 2024) - P1 | "As a frequent alteration identified in both PDAC and pancreatic premalignancy, mutant KRAS (mKRAS) has emerged as a potential target for immune-based interception strategies in individuals at high risk of developing pancreatic cancer. This is a single-arm, open-label, second-in-human phase I study of a pooled synthetic long peptide (SLP) vaccine with poly-ICLC adjuvant targeting up to six mKRAS subtypes (G12D, G12R, G12V, G12A, G12C, G13D) in patients with hereditary predisposition to developing PDAC (NCT05013216)... For the first time, we demonstrate mKRAS-specific T cell responses induced by vaccination in a cohort of high-risk individuals with inherited predisposition to PDAC. These findings directly serve as proof-of-concept to advance vaccine strategies focused on intercepting the development of pancreatic cancer in high-risk populations. Support: Stand Up To Cancer, Lustgarten Foundation, and NIH/NCI."

Clinical • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IFNG • KRAS

Ultrasound-mediated blood-brain barrier modulation enhances T-cell access but requires immune activation for effective CNS immunity. (PubMed, bioRxiv) - "Systemic immune adjuvants (poly-ICLC and IL-2; PI) induced APC activation, promoted tissue-resident-memory-like differentiation and supported durable T-cell responses...In antigenically heterogeneous glioma models resistant to CAR T-cell therapy, combining PI with BBB modulation enhanced the efficacy of immunotherapy, which was mirrored by prolonged survival and endogenous tumour-specific T-cell responses, consistent with epitope spreading. Together, these findings define key limitations of LIPU+MB in enabling effective T-cell therapy and establish that BBB modulation must be coupled to systemic immune activation to support T-cell-mediated antitumour immunity in the CNS."

IO biomarker • Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • IL2

Ultrasound-mediated immune access requires systemic licensing to promote durable T-cell mediated immunity in the CNS (EANO 2026) - "BBB opening was induced by stereotactically guided LIPU+MB, and systemic immune activation by poly-ICLC and IL-2... LIPU+MB permits T-cell entry but is insufficient to generate durable antigen-specific T-cell immunity in the CNS. Systemic immune activation is required to license myeloid cells and sustain T-cell function within the CNS. Coordinating LIPU+MB-mediated spatial immune access with immune licensing overcomes immune exclusion and improves immunotherapy efficacy in brain tumors."

IO biomarker • Brain Cancer • Glioma • Oncology • Solid Tumor • B2M • IL2

Randomized phase I/II trial adjuvant CD40.HVAC, an immunotherapy engaging dendritic cells (DC), in patients with HPV16+ oropharyngeal carcinoma (OPC). (ASCO 2026) - P1/2 | "In cohorts 1 (n=11) and 2 (n=11), pts were randomized (5:1) to receive subcutaneously, Hiltonol® (1mg) adjuvanted CD40.HVac, 1 and 3 mg, respectively, or placebo, at W0, 4, 24. The safety and immunogenicity of CD40.HVac support further clinical development of this strategy in pts with HPV16+ OPC."

Clinical • IO biomarker • P1/2 data • Oncology • Oropharyngeal Cancer • Solid Tumor • CD40 • CD8 • GZMB • IFNG • IL2 • LAMP1 • PD-1

MYELOVAC: A Phase 1 Trial of a Personalized Peptide-Based Neoantigen Vaccination Platform in Combination With Hypomethylating Agent–Based Therapy for Patients With Acute Myeloid Leukemia in First Complete Remission Ineligible for Intensive Chemotherapy and Allogeneic Stem Cell Transplantation (SOHO 2026) - "Interventions: MYELOVAC integrates four antigen sources, shared LAAs—targeting WT1, PRAME, and cyclin A1—and personalized neoantigens derived from somatic mutations, splicing events, and gene fusions, and adapts the PGV001 platform shown by our group to be safe and immunogenic in solid cancers and myeloma. MYELOVAC represents the first personalized neoantigen peptide vaccine for AML. By targeting multiple antigen classes in combination with HMA-based therapy, which may enhance immune priming and improve vaccine response, this study aims to inform vaccination efforts in AML. Enrollment is anticipated in early 2027."

Clinical • Combination therapy • IO biomarker • P1 data • Tumor mutational burden • Tumor-specific neoantigens • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Melanoma • Multiple Myeloma • Oncology • Solid Tumor • Wilms Tumor • CCNA1 • IFNG • PRAME • TMB • WT1

Pembrolizumab and a Vaccine (ATL-DC) for the Treatment of Surgically Accessible Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Jonsson Comprehensive Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: Aug 2027 ➔ Aug 2026 | Trial primary completion date: Jul 2025 ➔ Aug 2026

Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Improved Deep Learning Segmentation of Pediatric Diffuse Midline Gliomas After Treatment. (PubMed, AJNR Am J Neuroradiol) - "Training DMG segmentation models with post-treatment scans substantially improves performance in longitudinal clinical trial imaging, enabling more accurate volumetric tracking and response assessment."

Journal • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

HCC 21-208: Prototype DAA/TAA Vaccine Targeting MUC1 for Immune Interception and Prevention in Ductal Carcinoma In Situ (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Finn, Olivera, PhD | Trial completion date: Mar 2029 ➔ Dec 2029 | Trial primary completion date: Aug 2026 ➔ Feb 2028

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • MUC1

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: Jul 2029 ➔ Nov 2030 | Trial primary completion date: Mar 2028 ➔ Nov 2029

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

Response to combined MEK and mTOR inhibition in refractory pediatric low-grade gliomas: a limited case series (ISPNO 2026) - "Case presentation: Patient 1 was a 24-year-old male with suprasellar KIAA1549-BRAF fused pilocytic astrocytoma previously treated with single agent carboplatin, trametinib, a failed re-trial of trametinib, and substantial progression through tovorafenib...Interventions included vinblastine, carboplatin/vincristine, MEK inhibitor, mTOR inhibitor, retrial of MEK inhibitor, Avastin, and clinical trial with poly-ICLC... Combination therapy with trametinib and everolimus has stabilized two refractory LGGs who were previously treated with MEKi therapy and failed to respond to retreatment. Treatment has been well tolerated after initial dose reductions."

Clinical • Astrocytoma • Brain Cancer • Glioma • Infectious Disease • Low Grade Glioma • Mucositis • Pediatrics • Pilocytic Astrocytoma • Solid Tumor • BRAF • FGFR1 • KIAA1549

Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Washington University School of Medicine | N=32 ➔ 64 | Trial completion date: Mar 2033 ➔ Jun 2034 | Trial primary completion date: Oct 2028 ➔ Jan 2030

Enrollment change • Trial completion date • Trial primary completion date • Bladder Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Tumor regression during sequential EGFR-TKI therapy following personalized peptide immunotherapy in EGFR-mutant NSCLC: a translational case report (EACR 2026) - "Peptides were administered SC with poly-ICLC adjuvant biweekly during induction (6 doses) followed by monthly maintenance (21 doses administered to date)...Subsequent initiation of osimertinib as sequential EGFR-TKI therapy was associated with sustained regression of both lung lesions and brain metastases, ongoing for > 9 months... This translational case provides proof-of-concept that personalized peptide vaccination can induce broad tumor-specific immunity in EGFR-mutant NSCLC and may be associated with enhanced responsiveness to subsequent targeted therapy. While the clinical benefit cannot be causally attributed to immune priming in a single-patient setting, this may be a plausible strategy to overcome therapeutic resistance in this traditionally immune-refractory tumor subtype and supports prospective evaluation of combined active immunotherapy and EGFR-targeted therapy approaches."

Case report • Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IFNG

SOLVE-01: An Experimental Medicine Multicenter Trial to Evaluate the Safety and Immunogenicity of Experimental Versus Authorized SARS-CoV-2 Vaccine Candidates as a Booster Dose in Healthy Participants Previously Vaccinated With Authorized mRNA SARS-CoV-2 Vaccines. (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A personalized neoantigen vaccine to reprogram the immune landscape of glioblastoma. (ASCO 2026) - P1 | " Patients with newly diagnosed GBM who were not on dexamethasone following gross total resection were enrolled across four cohorts. Up to 20 synthetic long peptides targeting personal neoantigens were selected per patient, and admixed with the adjuvant poly-ICLC (NeoVax)...MGMT-unmethylated patients (Cohorts 1A-C) received NeoVax plus pembrolizumab without temozolomide (TMZ) and differed by time of pembrolizumab initiation relative to NeoVax priming; MGMT-methylated patients (Cohort 1D) received standard TMZ and pembrolizumab was initiated after NeoVax priming... NeoVax generates durable T cell responses that traffic to GBM tumors, with circulating responses associated with improved survival. Ongoing studies are evaluating peripheral clonotype dynamics, remodeling of malignant cell states and the TME, and the spatial distribution of vaccine-reactive clonotypes, which may guide future combinatorial strategies in GBM."

IO biomarker • Tumor-specific neoantigens • Brain Cancer • Glioblastoma • Solid Tumor • IFNG • MGMT

Beyond priming: a sequential, feedback-guided adjuvant framework for therapeutic cancer peptide vaccines in immunologically cold tumors. (PubMed, Front Immunol) - "A Phase 0 immune-readiness step, potentially using IL-7 (e.g., CYT107), is intended to improve the baseline substrate before antigen exposure. Phase 1 priming uses peptide vaccination on a commonly used adjuvant backbone such as Montanide ISA-51 or poly-ICLC (Hiltonol), while radiation and/or STING-based strategies are treated as context-dependent enhancers rather than replacements for priming...Although organized as sequential phases, the framework is intended as a bottleneck-guided and iterative design logic in which phases may overlap, repeat, or be entered in partial parallel depending on the dominant biologic constraint. The central hypothesis is that vaccine programs that progress beyond priming into trafficking-competent and functionally sustained states are predicted to correlate more closely with disease control than programs judged mainly by early blood immunogenicity."

Journal • Oncology • CXCR3 • IL12A • IL15 • IL21 • IL7 • STING

A clinical study of a prototype DAA/TAA vaccine targeting MUC1 for immune interception and prevention in ductal carcinoma in situ. (ASCO 2026) - P1 | "The vaccine is composed of a 100aa long MUC1 peptide corresponding to 5 tandem repeats of 20 amino acids from the MUC1 variable number of tandem repeats region (VNTR), admixed with the poly-ICLC adjuvant Hiltonol. The vaccine group receives the MUC1 peptide vaccine series pre-op (at 0, 2, and 10 weeks) with optional tamoxifen or an aromatase inhibitor (AI)...Statistical analysis: Fisher's exact test will be performed at the one-sided α=0.05 for the primary immunogenicity endpoint for comparing the experimental arm to the control arm. ."

Clinical • Breast Cancer • Oncology • Solid Tumor • MUC1

SOLVE-01: An Experimental Medicine Multicenter Trial to Evaluate the Safety and Immunogenicity of Experimental Versus Authorized SARS-CoV-2 Vaccine Candidates as a Booster Dose in Healthy Participants Previously Vaccinated With Authorized mRNA SARS-CoV-2 Vaccines. (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: ANRS, Emerging Infectious Diseases

New P1 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Vaccination With Flt3L, Radiation, and Poly-ICLC (clinicaltrials.gov) - P1/2 | N=17 | Completed | Sponsor: Icahn School of Medicine at Mount Sinai | Recruiting ➔ Completed | N=56 ➔ 17 | Trial completion date: Mar 2025 ➔ Sep 2025

Enrollment change • Trial completion • Trial completion date • Breast Cancer • Head and Neck Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC) (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2030 ➔ Aug 2030 | Initiation date: May 2026 ➔ Aug 2026 | Trial primary completion date: May 2026 ➔ Aug 2030

Trial completion date • Trial initiation date • Trial primary completion date • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • DNAJB1 • PRKACA

A Clinical Study of a Prototype DAA/TAA Vaccine Targeting MUC1 for Immune Interception and Prevention in Ductal Carcinoma In Situ (ASBrS 2026) - P1 | "The vaccine is composed of a 100aa long MUC1 peptide corresponding to 5 tandem repeats of 20 amino acids from the MUC1 variable number of tandem repeats region (VNTR), admixed with the poly-ICLC adjuvant Hiltonol...The vaccine group receives the MUC1 peptide vaccine series preoperatively (at 0, 2, and 10 weeks) with optional tamoxifen or an aromatase inhibitor (AI)...There are 20 patients on study to date. Contact information for clinicians and patients with an interest in the clinical trial."

Clinical • Breast Cancer • Immunology • Oncology • ER • MUC1