DPV-001 / UbiVac - LARVOL DELTA

Addition of GITR Agonist to a Dark Matter Cancer Vaccine and anti-PD-1 Increases Regulatory T cell Numbers Without Appearing to Impact Therapeutic Efficacy (SITC 2025) - "Here we combined treatment groups for analysis of response to treatment and evaluated changes in PBMC.Methods Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) were randomized to receive a heterologous prime-boost regimen of DPV-001 with sequenced d.PD-1 (retifanlimab every 4 weeks), with or without a GITR agonist (INCAGN-1949 every 2 weeks). This occurred in the absence of a significant increase in the absolute numbers of CD3, CD4, or CD8 T cells.Conclusions DPV-001 in combination with delayed PD-1 blockade ± GITR agonist demonstrated promising clinical activity in HNSCC, with response rates of 56% in PD-1 naïve and 33% in PD-1 refractory patients. While not appearing to impact clinical efficacy of the treatment, the significant increase in peripheral blood Treg numbers in patients receiving GITR agonist underscores the complexities that need to be appreciated when developing combination immunotherapies."

Clinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

Unveiling the Non-Canonical Dark Immunopeptidome of Head and Neck Squamous Cell Carcinoma (HNSCC) and Non-Small Cell Lung Cancer (NSCLC) using Mass Spectrometry and WatchMaker Total RNA-Seq (SITC 2025) - "Some of these dark antigens are contained in the DPV-001 vaccine administered to patients with this cancer. Current efforts are evaluating which antigens are immunogenic and whether they have oncogenic properties."

IO biomarker • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

UbiVac Presents 1st Report of In Vivo Generated T Cell Receptor (TCR) to Dark Genome-Derived Cancer’s Dark Matter (Firstwordpharma Press Release) - P=NA | N=NA | "UbiVac’s lead clinical-stage immunotherapy, DPV-001, was first evaluated as adjuvant therapy for non-small cell lung cancer in an NCI-funded trial. At AAI 2025, UbiVac presented a landmark finding from that study: 1. A Dark Matter antigen—derived from the non-coding, or 'dark,' genome—was identified in the patient’s tumor. 2. DPV-001 contained this specific dark matter antigen and induced, in the patient, a tumor-destructive T cell receptor (TCR) against it. 3. The TCR response occurred without adverse events, suggesting selectivity for cancer cells and sparing of normal tissue. 4. The patient remains alive and disease-free 10 years post-treatment."

Clinical data • Non Small Cell Lung Cancer

Identification of a TCR to a non-canonical peptide (NCP) presented by the autologous non-small cell lung cancer (NSCLC) following an immunotherapy that includes canonical and NCPs. (IMMUNOLOGY 2025) - "Here we studied the immune response of a patient with NSCLC that received adjuvant treatment with DPV-001 immunotherapy that contained canonical and non-canonical antigens... The detection of a T cell response to a NCP presented by the patient's cancer expands the range of possible cancer antigens that can be targeted with the potential to improve outcomes for patients with cancer.Keywords: Animals Human; Molecules Cell Surface Molecules T Cell Receptors; Techniques/Approaches Molecular Biology; Tissues Lung"

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Off-the-shelf dark matter immunotherapy in head & neck cancer: mechanistic insights and clinical efficacy (SITC 2024) - P1 | "Methods Patients were randomized to receive heterologous prime-boost DPV-001 + sequenced d.PD-1 (retifanlimab Q4W) +/- GITR agonist (INCAGN-1949 Q2W). Ongoing studies are directed at unraveling the nature of the antigens recognized (canonical or dark matter), and whether they persist. Ethics Approval This study was approved by Providence Health System's Ethics Board; approval number 2020000480."

Clinical • Late-breaking abstract • Head and Neck Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Promising Phase Ib Data for UbiVac’s DPV-001 in Combination Immunotherapy for Head and Neck Squamous Cell Cancer (EIN News) - P1b | N=56 | NCT04470024 | "56% objective clinical response rate and a progression-free survival of +9.3 months for patients receiving DPV-001 combination immunotherapy as first line treatment for recurrent or metastatic HNSCC; Patients that had not responded to prior treatment with anti-PD-1 had a 33% objective clinical response rate and a progression-free survival of +6.2 months."

P1 data • Squamous Cell Carcinoma of Head and Neck

Dr Leidner on the Multivalent Vaccine DPV-001 in Advanced or Metastatic HNSCC (OncLive) - P1 | N=56 | NCT04470024 | "In the study, 18 patients received DPV-001 with sequenced a novel PD-1 therapy, INCMGA00012. Nine of these patients also received the GITR agonist INCAGN01876 starting on day 1....Leidner notes that the overall response rate (ORR) for patients with PD-1–naive disease was 55.5% (n = 5/9), and the ORR was 33.3% (n = 3/9) for patients previously treated with PD-1 therapy patients."

P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Providence Health & Services | Active, not recruiting ➔ Recruiting | Trial completion date: Jul 2024 ➔ Dec 2027 | Trial primary completion date: Dec 2023 ➔ Dec 2025

Checkpoint inhibition • Enrollment open • Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

An off-the-shelf multivalent vaccine containing cancer's dark matter, DPV-001, combined with PD-1 +/- GITR in head & neck cancer: safety, efficacy, and immunodynamics from the phase 1 GITRVax trial (AACR 2024) - "Preclinical studies identified increased therapeutic efficacy when this vaccine strategy was combined with anti-PD-1 and anti-GITR, leading to this clinical trial for patients with advanced or metastatic HNSCC. Following safety run-in, eligible pts were randomly assigned 1:1 to receive DPV-001 +/- GITR agonist mAb (INCAGN-1949; q2wks). All received sequenced PD-1 mAb (retifanlimab; q4wks) starting D15... This 18 pt trial of DPV-001 and sequenced PD-1 +/- GITR shows a promising RR and evidence of increased activation and expansion of effector T cells in PBL and tumor. Upregulation of LAG-3 and TIM3 by T cells that infiltrate the tumor and have increased in number, provide a rationale for including inhibitors for both in this treatment strategy. Current efforts include evaluating whether immune responses target shared non-canonical alternative neoantigens, or Dark Matter, contained in DPV-001, and whether synchronized antibody and cellular response is evidenced."

Clinical • IO biomarker • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • GZMB • HAVCR2 • IFNG • LAG3 • PD-1

Multi-parametric assessment of the immune response to a trio immunotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (SITC 2023) - P1 | "Methods Patients received DPV-001, with sequenced checkpoint inhibition (aPD-1 mAb; retifanlimab), with or without aGITR agonist mAb (INCAGN1876), in recurrent or metastatic HNSCC (NCT04470024). Increased expression of LAG3 by T cells that infiltrate and have expanded in the tumor, provide a rationale for including anti-LAG-3 in this treatment strategy. Future plans include evaluating whether immune responses target shared non-canonical alternative neoantigens, or Dark Matter, contained in DPV-001 and whether antibody responses identify targets of cellular immunity."

Clinical • IO biomarker • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ENTPD1 • GZMB • IFNG • ITGAE

Characterizing cancer’s dark matter, short-lived proteins, and defective ribosomal products, presented by cancer and contained in the DPV-001 cancer vaccine (SITC 2023) - "The discovery of NCP derived from supposed non-coding regions that are not expressed in the thymus, represent a novel class of potentially shared alternative cancer neoantigens. Their association with malignant processes may provide them properties similar to that of driver mutations, and increase their relevance as cancer vaccine targets."

IO biomarker • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov) - P1 | N=56 | Active, not recruiting | Sponsor: Providence Health & Services | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Enrollment closed • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

Preliminary immunological monitoring of first-in-human immunotherapy-trio for advanced head and neck squamous cell carcinoma (AACR 2022) - P1 | "Here we report preliminary immunological analyses of patients enrolled in a first-in-human immunotherapy-trio study of multivalent autophagosome vaccine (DPV-001), with sequenced checkpoint inhibition (anti-PD-1; retifanlimab), with/without anti-GITR agonist (INCAGN-1949), in recurrent or metastatic HNSCC (NCT04470024). Peripheral blood (PB) and sera are collected regularly and PB are evaluated by flow cytometry. We previously reported immunological monitoring of a phase I/II trial of an autophagosome cancer vaccine (DPV-001) containing more than 300 shared cancer antigens, as adjuvant therapy for NSCLC. Vaccination induced or augmented immune responses to more than 50 cancer antigens shared with head and neck squamous cell carcinoma (HNSCC). Preclinical studies combining this cancer vaccine with αGITR agonist and αPD-1 augmented therapeutic efficacy [PMID: 31747946], and provided the rationale for the current study."

P1 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

Trial in progress: First-in-human immunotherapy-trio for advanced head and neck squamous cell carcinoma (AACR 2023) - P1 | "We hypothesize that addition of aGITR to DPV-001 vaccine will augment expansion of reactive CD4 and CD8 T cells, attenuate contraction of this response, and improve the therapeutic effect of treatment, and will result in the development of a coordinated T and B cell response to some of the same proteins, detectable using a cutting-edge seromics approach, as a window to TCR target identification for immunodynamic tracking of induced anti-cancer responses at an advanced level. Patient recruitment began in August 2022, for this first-in-human immunotherapy-trio study of DPV-001, with sequenced checkpoint inhibition (aPD-1 mAb; retifanlimab), with or without aGITR agonist mAb (INCAGN-1949), in recurrent or metastatic HNSCC (NCT04470024)...Initial safety lead-in (n = 3+3 per arm), will be followed by phase Ib expansion of one/both arms if immunologically promising, 28 patients per arm, futility if <4/15 responses.Study DrugsCyclophosphamide 300mg/m2 IV, priming Day..."

Metastases • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • TNFA

[VIRTUAL] An Immunotherapy Trio in advanced HNSCC for coordinated B and T cell antigen response (SITC 2020) - P1 | "We have developed a cancer vaccine, DPV-001, that contains more than 300 proteins for genes overexpressed by HNSCC, encapsulated in a CLEC9A-targeted microvesicle and containing TLR/NOD agonists and DAMPs...Our planned clinical trial will vaccinate and boost the induced responses by costimulation with anti-GITR and then sequence in delayed anti-PD-1 to relieve checkpoint inhibition. MAP bead arrays and the peptidome library generated above will be used to assess anti-cancer B and T cell responses."

IO biomarker • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • PD-L1

Development of a Vaccine to Intercept Oral Cancer (SITC 2022) - "A clinical trial of a similar vaccine, DPV-001, administered as a single agent as adjuvant therapy for NSCLC, documented induction of immunity to a large number of cancer antigens contained in the vaccine and did not identify serious adverse events. Based on data summarized above, we propose to vaccinate patients with dysplastic lesions and investigate whether vaccination reduces lesion recurrence."

IO biomarker • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Solid Tumor

UbiVac Announces Preliminary Immunological Data from 1st-In-Human Trial of DPV-001 Immunotherapy Trio for Advanced HNSCC (EIN News) - "Data from Clinical Trial of DPV-001 & Anti-PD-1 +/- anti-GITR for Head & Neck Squamous Cell Cancer (HNSCC) Presented at American Association for Cancer Research."

P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] An Immunotherapy Trio in advanced HNSCC for coordinated B and T cell antigen response (SITC 2020) - P1 | "We have developed a cancer vaccine, DPV-001, that contains more than 300 proteins for genes overexpressed by HNSCC, encapsulated in a CLEC9A-targeted microvesicle and containing TLR/NOD agonists and DAMPs...Our planned clinical trial will vaccinate and boost the induced responses by costimulation with anti-GITR and then sequence in delayed anti-PD-1 to relieve checkpoint inhibition. MAP bead arrays and the peptidome library generated above will be used to assess anti-cancer B and T cell responses."

IO biomarker • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • PD-L1

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Providence Health & Services; Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4

An Investigational Immuno-Therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Participants With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2; N=171; Completed; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Completed

Trial completion • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

An Investigational Immuno-Therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Participants With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2; N=207; Recruiting; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Recruiting; Trial completion date: Aug 2022 ➔ Oct 2024; Trial primary completion date: May 2021 ➔ Jul 2023

Clinical • Combination therapy • Enrollment open • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Triplet Immunotherapy for Metastatic Triple Negative Breast Cancer Presented at Chinese Society for Clinical Oncology (EIN Presswire) - “Dr. Fox will then review preclinical and clinical data that led to the development of a first-in-human triplet cancer immunotherapy trial. This multicenter randomized clinical trial includes: 1) a cancer vaccine, DPV-001...2) a T cell agonist, anti-OX40, that can boost anti-cancer immune responses, followed by 3) delayed administration of anti-PD-1, to relieve checkpoint inhibition...Dr. Fox will also discuss a second triplet cancer immunotherapy under development at the Earle A. Chiles Research Institute…for investigation as treatment for advanced head and neck squamous cell cancer (HNSCC). This trial also plans to use DPV-001 to prime an immune response to a spectrum of HNSCC antigens, a T cell agonist, anti-GITR, and a checkpoint blocker.”

Clinical data • Preclinical • Trial status • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

An Investigational Immuno-therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Patients With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2; N=170; Active, not recruiting; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Oncology • Solid Tumor

Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov) - P1; N=56; Not yet recruiting; Sponsor: Providence Health & Services

Checkpoint inhibition • New P1 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

UbiVac announces clinical trial collaboration with Bristol Myers Squibb on combination immunotherapy for advanced triple negative breast cancer (Businesswire) - "UbiVac, Inc…announced it has entered into a clinical trial collaboration with Bristol Myers Squibb (NYSE:BMY) to evaluate the safety, tolerability, and preliminary efficacy of UbiVac’s investigational product, DPV-001™, a first-in-class cancer vaccine that exploits autophagy, in combination with Bristol Myers Squibb’s anti-OX40 (BMS-986178) combined with sequenced administration of the programmed death-1 (PD-1) immune checkpoint inhibitor, Opdivo (nivolumab). The Phase 1b multicenter trial will test the hypothesis that combination immunotherapy with the DPV-001 cancer vaccine and anti-OX40 will augment anticancer immunity in patients with advanced triple negative breast cancer."

Licensing / partnership • Breast Cancer • Oncology • Triple Negative Breast Cancer