Hiltonol (poly-ICLC) / Oncovir - LARVOL DELTA

IRB00210915: Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Resected Mismatch Repair Protein (MMR-p) Colorectal and Pancreatic Cancer (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 ➔ Jun 2027 | Trial primary completion date: Aug 2025 ➔ Jun 2027

Mismatch repair • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Early Results from a Phase 1 Clinical Study of a Cancer Vaccine Targeting Tumor Associated Antigen MUC1 in Ductal Carcinoma in Situ for Immune Interception of Breast Cancer (SABCS 2025) - 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...ConclusionMUC1 peptide vaccine given in the premalignant DCIS setting is safe in the first 7 patients to receive the vaccine. The 86% immune response rate predicts a high rate of response, which will allow us to study immune mechanisms activated by the vaccine, including changes in the DCIS microenvironment."

Clinical • P1 data • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • 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: Nov 2028 ➔ Jul 2029 | Trial primary completion date: Nov 2028 ➔ Mar 2028

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

Pembrolizumab in combination with the multipeptide vaccine IMA950 adjuvanted with Poly-ICLC for relapsing glioblastoma: a randomized phase I/II trial (IMA950-106) (SNO 2025) - "Additionally, a distinct cluster of CD8⁺ IL7Rhi T cells was identified in both pre- and post-treatment samples across both treatment arms. Altogether, the IMA950/Poly-ICLC vaccine administered with or without pembrolizumab is safe but did not significantly impact patient survival."

Clinical • Combination therapy • IO biomarker • P1/2 data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD4 • CD8 • IL7R • SPP1

Pembrolizumab in combination with the multipeptide vaccine IMA950 adjuvanted with Poly-ICLC for relapsing glioblastoma: a randomized phase I/II trial (IMA950-106) (WFNOS 2025) - "Additionally, a distinct cluster of CD8⁺ IL7Rhi T cells was identified in both pre- and post-treatment samples across both treatment arms. Altogether, the IMA950/Poly-ICLC vaccine administered with or without pembrolizumab is safe but did not significantly impact patient survival."

Clinical • Combination therapy • IO biomarker • P1/2 data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Solid Tumor • CD4 • CD8 • IL7R • SPP1

Checkpoint Immunotherapy Is Associated with Preferential Activation of Tumor-Antigen Specific CD4+ T Cells in MDS (ASH 2023) - "Background: Patients with intermediate and higher-risk MDS are generally treated with the DNA hypomethylating agents (HMAs) azacytidine and decitabine...This open-label, non-randomized single center Phase 1 study used an HLA unrestricted NY-ESO-1 vaccine (CDX-1401 (1 mg) + poly-ICLC (1.8 mg)) in combination with standard dose decitabine (20mg/m2/d x 5 days) and nivolumab (3 mg/kg every 2 weeks), 4 cycles of combination therapy were planned on study; patients deriving clinical benefit could continue treatment at the discretion of the treating physician... These results suggest that the use of immunotherapy to induce effective, cytotoxic anti-tumor T cell responses depends upon the myeloid immunologic milieu in MDS patients. The critical importance of cDC1 function has recently been described and appreciated in the context of solid tumor immunotherapy. The observation of both numerical and functional defects of this cell population in patients with myeloid neoplasia..."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor • CD4 • CD8 • CTAG1B

PRELIMINARY RESULTS OF A MULTICENTRIC RANDOMIZED PHASE I/II TRIAL HPV.DCVAX OF AN IMMUNOTHERAPY ENGAGING DENDRITIC CELLS (DC), CD40.HVAC, IN PATIENTS WITH HPV16-POSITIVE OROPHARYNGEAL CARCINOMA (OPC) (IPVC 2025) - P1/2 | "In cohorts 1 (n=11) and 2 (n=11), patients were randomized (5:1) to receive subcutaneously, Hiltonol® (1mg) adjuvanted CD40.HVac, 1 and 3 mg respectively, or placebo, at W0, 4, and 24. CD40.HVac is an innovative way to deliver oncoproteins and to engage DC to improve immunogenicity. The safety and robust immunogenicity of CD40.HVac support further clinical development of this strategy in patients with advanced OPC."

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

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

Trial completion • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A personalized neoantigen vaccine induces anti-tumor T cell responses in patients with PD-1/PD-L1 inhibitor refractory metastatic melanoma (SITC 2025) - "This phase I study evaluated the immunologic impact of the neoantigen peptide vaccine PNV-021 in PD-1-refractory melanoma.Methods Eight patients received up to 20 neoantigen peptides, predicted to bind HLA class I/II, every four weeks alongside Poly-ICLC and nivolumab. b) Week 12 biopsies from all patients showed increased CD163+ macrophage and CD3+ T cell infiltration compared to enrollment biopsiesAbstract 602 Figure 2Request permissionsUniform Manifold Approximation and Projection (UMAP) of the phenotypic distribution of tumor-reactive T cells. Tumor-reactive TCRs expressed genes associated with T cell activation and exhaustion, including the previously characterized tumor-reactive T cell signature markers CXCL13 and ENTPD1"

Clinical • IO biomarker • Metastases • Tumor-specific neoantigens • Melanoma • Oncology • Solid Tumor • CD163 • CDC37 • CXCL13 • DCT • ENTPD1 • ERN1 • HSP90AB1 • IFNG • PRAME • Tyrosinase

A phase I clinical trial of a personalized neoantigen vaccine in PD-1 inhibitor refractory metastatic melanoma (SITC 2025) - "Increases in tumor immune infiltration was observed in both responding and non-responding patients.Conclusions PNV-21, a personalized neoantigen peptide vaccine, combined with nivolumab and weekly Poly-ICLC, was demonstrated to be well tolerated and safe. Furthermore, the treatment led to anti-tumor immune activation and objective responses in heavily pretreated patients with metastatic melanoma. Vaccine-induced immune responses were detectable in patients with and without objective clinical benefit.Acknowledgements Funding for this trial was provided by Amazon, and we would llike to thank patients and their families.Ethics Approval The study was approved by the Fred Hutchinson Cancer Center IRB (approval number RG1121642).Abstract 608 Figure 1Request permissionsRegression of large tumor following vaccination in patient 6, residual tumor negative for melanoma by pathology of biopsy at 6 monthsAbstract 608 Figure 2Request permissionsRECIST changes from baseline, numbers..."

Clinical • Metastases • P1 data • Tumor-specific neoantigens • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • TLR3

Prostate cancer in situ autovaccination with the intratumoral viral mimic poly-ICLC: Modulating the cold tumor microenvironment. (PubMed, Med) - P1 | "Intratumoral poly-ICLC immunotherapy for PCa is safe and may modulate the tumor microenvironment, enhancing antitumor responses. These findings support larger, controlled trials to assess effects on long-term clinical outcomes."

Biomarker • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD20 • CD4 • CD8 • NCAM1 • PD-1

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 | Trial completion date: Dec 2027 ➔ Nov 2025

Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Study of the Immune Response of MUC1 (Mucin1) Peptide Vaccine for Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Olivera Finn | Trial completion date: Oct 2031 ➔ Oct 2032 | Trial primary completion date: Oct 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase Ib Study of Indirect Immunization with Oregovomab and Toll-like-Receptor-3 Stimulation with Hiltonol® in Patients with Recurrent Platinum-Resistant Ovarian Cancer. (PubMed, Curr Oncol) - " The safety and compatibility of combining oregovomab with Hiltonol® have been demonstrated in this study. The potential to enhance activity of chemotherapy using oregovomab indirect immunization and Hiltonol® stimulation is proposed."

Journal • P1 data • Platinum resistant • Cardiovascular • Fatigue • Hematological Disorders • Hypertension • Oncology • Ovarian Cancer • Pain • Solid Tumor • Thrombocytopenia • MUC16 • TLR3

Vaccine immunotherapy for glioblastoma: How can previous attempts guide us? (PubMed, Exp Neurol) - "Vaccine immunotherapy for GBM appears to depend on dendritic cells to achieve significant improvements in survival. The incorporation of innate immunity modulators such as GM-CSF and Poly-ICLC, along with stratification by MGMT-methylation, are promising. Although an expressive HR reduction was achieved, there are still primary scientific validity concerns, the residual hazard leads to a reserved prognosis and should be addressed by multimodal treatment approaches."

Journal • Review • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • CSF2 • MGMT

P30-EPS peptide vaccine is safe and immunogenic in newly diagnosed glioblastoma: a phase 1b trial (EANO 2025) - "Adjuvant temozolomide was omitted, and instead patients received intramuscular P30-EPS, 300 mg (n=6) in the first cohort and 400 mg (n=12) in the second cohort, scheduled in “priming” and “booster” phases to enhance the expansion of vaccine-specific T cells. P30-EPS administered with Hiltonol demonstrated a favorable safety profile and elicited vaccine-specific immune responses in patients with newly diagnosed glioblastoma. The 400 mg dose was associated with stronger immunogenicity and early signals of clinical activity. We will present clinical outcomes, including survival and MRI responses for all 18 patients, along with longitudinal 5′ scRNA VDJ TCR profiling of PBMCs and paired baseline and on-treatment tumor snRNA-seq."

IO biomarker • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BIRC5 • CD4 • CD8 • IFNG • MGMT

Adjuvant PVX-410 Vaccine and Durvalumab in Stage II/III Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

A Phase Ib Study of Indirect Immunization with Oregovomab and Toll-like-Receptor-3 Stimulation with Hiltonol in Patients with Recurrent Platinum-Resistant Ovarian Cancer (Multidisciplinary Digital Publishing Institute) - "Ten (67%) patients had disease progression, three (20%) had stable disease, and two were unevaluable. Early humoral response by week 6 was observed in seven of nine (77%) patients, median progression-free survival was 2.7 months (95% confidence interval [CI]: 2.2, 3.3), and median overall survival was 15.0 months (95% CI: 8.2–23.9)."

P1 data • Platinum resistant • Ovarian Cancer

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 | Trial completion date: Sep 2033 ➔ Mar 2033

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

KRAS Peptide Vaccine Combined With Chemotherapy, Nivolumab and Ipilimumab in Advanced KRAS Mutated Non-Small Cell Lung Cancer (IASLC-WCLC 2025) - "The vaccine consists of poly-ICLC adjuvant admixed with pooled synthetic long peptides (SLPs) corresponding to six common mKRAS subtypes: G12D, G12R, G12V, G12A, G12C, and G13D. Correlative studies will apply multi-omic approaches to identify markers of response and resistance in tumor and plasma samples. The study has enrolled 5 patients to treatment with the combination of ipilimumab and nivolumab with KRAS-mutant vaccine and we will now procced to enroll additional patients to the amendment described herein."

IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KEAP1 • KRAS • STK11

Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Nov 2026 ➔ Nov 2027 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Breast Cancer • Cutaneous Melanoma • Eye Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Mucosal Melanoma • Non Small Cell Lung Cancer • Ocular Melanoma • Oncology • Solid Tumor • BRAF • ER • HER-2 • PGR

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) | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Sep 2024 ➔ Sep 2026 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma

Safety and Immunogenicity of Personalized Genomic Vaccine and Tumor Treating Fields (TTFields) to Treat Glioblastoma (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: Adilia Hormigo | Trial completion date: May 2025 ➔ May 2029 | Trial primary completion date: Jul 2020 ➔ May 2029

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

Pembrolizumab and a Vaccine (ATL-DC) for the Treatment of Surgically Accessible Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2025 ➔ Aug 2026

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