Hiltonol (poly-ICLC)

P1, N=50, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.

P1/2, N=16, Not yet recruiting, VA Office of Research and Development | Trial primary completion date: Mar 2026 --> Jun 2026

P2, N=60, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=19, Active, not recruiting, Massachusetts General Hospital | Phase classification: P1b --> P1 | Trial completion date: Jun 2023 --> Sep 2024 | Trial primary completion date: Jun 2023 --> Sep 2024

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

P1, N=6, Not yet recruiting, Jonsson Comprehensive Cancer Center

P1, N=25, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting

P1, N=10, Recruiting, Marina Kremyanskaya | Trial completion date: Jan 2025 --> Mar 2026 | Trial primary completion date: Jan 2024 --> Mar 2026

P2, N=20, Recruiting, University of Alabama at Birmingham | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2025 --> Feb 2026

P1, N=13, Active, not recruiting, Albert Einstein College of Medicine | Trial completion date: May 2024 --> May 2025

P1, N=50, Recruiting, Finn, Olivera, PhD | Not yet recruiting --> Recruiting | Trial completion date: Jul 2027 --> Aug 2028

P1, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Dec 2024 --> Aug 2025

P1/2, N=50, Completed, Sabine Mueller, MD, PhD | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Dec 2023 | Trial primary completion date: Nov 2024 --> Dec 2023

P1/2, N=16, Not yet recruiting, VA Office of Research and Development | Trial completion date: Dec 2028 --> Apr 2028 | Trial primary completion date: Dec 2025 --> Mar 2026

P1/2, N=33, Completed, Craig L Slingluff, Jr | Recruiting --> Completed

P1, N=20, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Nov 2024 --> Nov 2025

P1, N=50, Not yet recruiting, Finn, Olivera, PhD

P1, N=22, Active, not recruiting, Massachusetts General Hospital

P1, N=22, Active, not recruiting, Massachusetts General Hospital | Phase classification: P1b --> P1

In this study, we present updated findings from a phase 2 clinical trial (NCT02078648) evaluating SL-701+poly-ICLC+bevacizumab, where the 12-month overall survival (OS) was 50%. These qualitative differences in the immune response, detectable as early as week 8 post treatment, may serve as biomarkers for monitoring and predicting survival. Deep sequencing of SL-701-specific T-cells is planned.

P1, N=60, Active, not recruiting, James Felker | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=50, Completed, Craig L Slingluff, Jr | Active, not recruiting --> Completed

P2, N=25, Recruiting, James Felker | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

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 provides a possible explanation for the disappointing efficacy of immunotherapies in this disease state.

Results A young male with histologically confirmed FLC was treated with a 24mer DNAJB1-PRKACA synthetic long peptide vaccine with poly-ICLC in combination with ipilimumab and nivolumab on our clinical trial, NCT04248569. Our studies provide a framework to identify these responses in peripheral blood samples from treated patients and thereby determine correlates of response to therapy. Additionally, the defined fusion-specific TCRs show potential for translation to cellular therapies for FLC, highlighting multiple immunotherapeutic strategies that could benefit FLC patients.

P1/2, N=22, Active, not recruiting, Craig L Slingluff, Jr | Recruiting --> Active, not recruiting

P1, N=28, Active, not recruiting, Jennie Taylor | Trial completion date: Aug 2023 --> Aug 2024

P1/2, N=16, Not yet recruiting, VA Office of Research and Development

The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.

FLC-Vac, consisting of a 24 amino acid peptide targeting the DNAJB1-PRKACA fusion with adjuvant poly-ICLC, is administered on weeks 0, 1, 2, 3, 6, 9 during the priming phase of the study and NIVO, 3 mg/kg, followed by IPI, 1 mg/kg, are administered every 3 weeks for 4 doses. Conclusions This first-in human study provides initial evidence of safety and clinical efficacy of a vaccine targeting the DNAJB1-PRKACA fusion plus immune checkpoint inhibitor therapy for FLC. T cell responses are consistent with neoantigen-specific immunity against the DNAJB1-PRKACA chimera.

P1, N=36, Recruiting, Mustafa Khasraw, MBChB, MD, FRCP, FRACP | Not yet recruiting --> Recruiting

P1, N=5, Active, not recruiting, Craig L Slingluff, Jr | Recruiting --> Active, not recruiting | N=32 --> 5 | Trial completion date: Jun 2025 --> Feb 2024 | Trial primary completion date: Dec 2024 --> Feb 2024

P1, N=13, Active, not recruiting, Adilia Hormigo | Trial completion date: May 2023 --> May 2024

Flow cytometry of the tumor-infiltrating lymphocytes showed decreased Treg cells and monocytic myeloid-derived suppressor cells, increased CD8 T cells, enhanced granzyme B expression, and reduced exhaustion-related markers PD-1 and Lag-3 on CD8 T cells in the combination group. These findings provide a strong rationale for conducting clinical studies of using neoantigen vaccination in combination with anti-PD-1 to treat patients with HCC.

P1, N=0, Withdrawn, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=12 --> 0 | Trial completion date: Apr 2028 --> May 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Apr 2027 --> May 2023

P1, N=56, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=12 --> 56 | Trial completion date: Mar 2024 --> Mar 2027 | Trial primary completion date: Mar 2024 --> Mar 2027

P1/2, N=30, Recruiting, Craig L Slingluff, Jr | Trial completion date: Feb 2023 --> Sep 2024 | Trial primary completion date: Feb 2023 --> Sep 2023

P1, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Mar 2024

P1, N=14, Active, not recruiting, Nicholas Butowski | Trial completion date: Dec 2022 --> Dec 2030

This novel therapeutic vaccine was safe as perioperative immunotherapy for patients with HCC and has the potential to strongly induce CD8+ T cells infiltration into tumors.