PGV-001 / Icahn School of Medicine at Mount Sinai - LARVOL DELTA

Atezolizumab plus personalized neoantigen vaccination in urothelial cancer: a phase 1 trial. (PubMed, Nat Cancer) - P1 | "In an attempt to stimulate antitumor immunity, we evaluated atezolizumab (anti-programmed cell death protein 1 ligand 1) in combination with PGV001, a personalized neoantigen vaccine, in participants with urothelial cancer. Neoantigen vaccination plus ICI was feasible and safe, meeting its endpoints, and warrants further investigation. ClinicalTrials.gov registration: NCT03359239 ."

Journal • P1 data • Fatigue • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Personalized cancer vaccine shows potential in myeloma, solid tumors (Rare Cancer News) - P1 | N=13 | NCT02721043 | "A personalized cancer vaccine called PGV001 showed potential in combating several types of cancer, both solid tumors and blood malignancies like myeloma, in a small Phase 1 clinical trial....Preliminary findings also showed that, in all patients who received the vaccine, the immune system showed signs of a response against the neoantigens, implying that the vaccine was activating the immune system to go after the cancer as designed. These data highlight 'the potential of PGV001 for safely inducing targeted immunity,' the researchers wrote. At five years of follow-up, six of the trial’s participants are alive, and three remain free of cancer."

P1 data • Multiple Myeloma • Solid Tumor

PGV001, a multi-peptide personalized neoantigen vaccine platform: Phase I study in patients with solid and hematological malignancies in the adjuvant setting. (PubMed, Cancer Discov) - P1 | "Our data indicates that PGV001 is feasible and safe, with 13 out of 14 enrolled patients receiving the vaccine and 11 completing the treatment. 100% of vaccinated patients developed targeted T cell and B cell responses highlighting the capacity of OpenVax to predict immunogenic neoantigens and the potential of PGV001 for safely inducing targeted immunity."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Oncology

PGV-Prostate: The Safety and Tolerability of PGV001-based Personalized Multi-peptide Vaccines in the Adjuvant Setting. (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Ashutosh Kumar Tewari | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Immunogenicity of Atezolizumab plus personalized neoantigen vaccination (PGV-001) in patients with urothelial cancer in adjuvant vs metastatic setting (AACR 2024) - P1 | "These data indicate that vaccination with personalized neoantigens in combination with systemic anti-PD-L1 can induce neoantigen-focused T cell responses in both adjuvant and metastatic disease settings. However, the single arm nature of the trial, and sample size, preclude definitive assessment of the contribution of the components of the combination therapy. Future studies will investigate the efficacy of this approach on a larger scale with pre- and on-treatment analyses of treatment-driven immunomodulation."

Clinical • Late-breaking abstract • Metastases • Tumor-specific neoantigens • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD4 • CD8 • IFNG

Atezolizumab plus personalized neoantigen vaccination (PGV001) in patients with urothelial cancer. (ASCO-GU 2024) - P1 | "After an initial priming vaccination course (cycle 1), pts received atezolizumab 1200 mg intravenously every 3 weeks for up to 12 months (adjuvant) or 24 months (metastatic) and PGV001 with poly-ICLC on subsequent days every 3 weeks during cycles 2-5 and 9. Atezolizumab plus PGV001 was feasible, safe, and induced neoantigen-specific T cell immunity in all evaluated pts. To our knowledge, this is the first report of combination neoantigen vaccination plus ICI in the adjuvant setting in UC. Neoantigen vaccination plus ICI warrants further evaluation."

Clinical • Tumor-specific neoantigens • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD4 • CD8 • IFNG

Immunogenicity of PGV_001 neoantigen vaccine in a Phase-I clinical trial, across various types of cancers in adjuvant setting (AACR 2023) - P1 | "Approximately 10 peptides were synthesized per patient, and a mixture of these peptides was administered as 10 subcutaneous and intradermal vaccines over 27 weeks in combination with poly-ICLC and helper Tetanus peptide as adjuvants. We have established a platform for generating personalized neoantigen vaccines. 100% of the vaccinated patients developed an immune response specific to the vaccine neoantigens predicted by OpenVax. Subjects who received treatment experienced mild Grade 1 or 2 adverse reactions as per the CTEP v 4.0 NCI CTCAE."

Clinical • IO biomarker • P1 data • Tumor-specific neoantigens • Bladder Cancer • Brain Cancer • Breast Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Head and Neck Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • CD4 • CD8 • IFNG

[VIRTUAL] PGV-001: A Phase 1 Trial of a Personalized Neoantigen Peptide Vaccine for the Treatment of Malignancies in the Adjuvant Setting. (SITC 2020) - P1 | "Trial Registration NCT02721043. Conclusions A personalized neoantigen vaccine of synthetic mutant peptides and adjuvant poly-ICLC was successfully synthesized for 15 patients and administered successfully to 87% patients over the course of 27 weeks. The vaccine was well tolerated, and T cell expansion and reactivity to synthetic neoantigens confirms immunogenicity of neoantigens identified with OpenVax."

Clinical • IO Biomarker • P1 data • Tumor-specific neoantigens • Oncology • IL2 • TNFA

PGV-Prostate: The Safety and Tolerability of PGV001-based Personalized Multi-peptide Vaccines in the Adjuvant Setting. (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Ashutosh Kumar Tewari | Trial completion date: Dec 2031 ➔ Dec 2027

Combination therapy • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Atezolizumab Given in Combination With a Personalized Vaccine in Patients With Urothelial Cancer (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Matthew Galsky | Recruiting ➔ Completed | N=15 ➔ 10

Combination therapy • Enrollment change • Trial completion • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A phase I study of the safety and immunogenicity of a multi-peptide personalized genomic vaccine in the adjuvant treatment of solid tumors and hematological malignancies (SITC 2018) - P1; "PGV001_002 (head and neck squamous cell cancer), who has completed vaccination, received 10 doses of vaccine comprising 10 long peptides (LP) combined with poly-ICLC (tolllike receptor-3 agonist) intracutaneously. Conclusions The PGV001 vaccine in our first patient showed both safety and immunogenicity, eliciting CD4+ and CD8+ responses to the vaccine peptides. As we enroll additional patients in this clinical trial, and perform deeper phenotyping of their tumor-reactive T cells, we will learn the determinants necessary for successful induction of immunity, while informing future immunotherapeutic approaches and rational combinations"

Clinical • IO biomarker • P1 data • Head and Neck Cancer • Leukemia

[VIRTUAL] PGV-001: A Phase 1 Trial of a Personalized Neoantigen Peptide Vaccine for the Treatment of Malignancies in the Adjuvant Setting. (SITC 2020) - P1 | "Trial Registration NCT02721043. Conclusions A personalized neoantigen vaccine of synthetic mutant peptides and adjuvant poly-ICLC was successfully synthesized for 15 patients and administered successfully to 87% patients over the course of 27 weeks. The vaccine was well tolerated, and T cell expansion and reactivity to synthetic neoantigens confirms immunogenicity of neoantigens identified with OpenVax."

Clinical • IO biomarker • P1 data • Tumor-specific neoantigens • Oncology • IL2 • TNFA

[VIRTUAL] PGV-001: A phase I trial of a multipeptide personalized neoantigen vaccine in the adjuvant setting (AACR-II 2020) - P1 | "The vaccine was administered over the course of 6 months, given in combination with poly-ICLC as the adjuvant. The PGV-001 personalized neoantigen vaccine was successfully administered to 13 patients, where each patient’s neoantigen load was adequate for vaccine synthesis. While we have demonstrated the computational feasibility of identification of neoantigens for inclusion in the PGV-001 genomic vaccine, clinical outcomes will be reported separately."

Clinical • P1 data • Tumor-specific neoantigens • Breast Cancer • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Thoracic Cancer • CD8

[VIRTUAL] An adjuvant personalized neoantigen peptide vaccine for the treatment of malignancies (PGV-001) (AACR 2021) - P1 | "Peptides were administered over the course of 27 weeks with poly-ICLC and a tetanus helper peptide. PGV-001 was successfully synthesized for 15 patients and administered successfully to 13 patients without significant adverse events. Immune monitoring of immunogenicity is ongoing, with initial analysis demonstrating induction of neoantigen-specific CD4 and CD8 T cell expansion."

Clinical • IO biomarker • Late-breaking abstract • Tumor-specific neoantigens • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL2 • TNFA

A phase I study of the safety and immunogenicity of a multi-peptide personalized genomic vaccine in the adjuvant treatment of solid tumors and hematological malignancies. (ASCO 2019) - P1; " Patients who completed vaccination with PGV001_002 (head and neck squamous cell cancer) received 10 doses of vaccine comprising 10 long peptides (LP) combined with poly-ICLC (toll-like receptor-3 agonist) intradermally. The PGV001 vaccine in our first patient showed both safety and immunogenicity, eliciting CD4+ and CD8+ responses to the vaccine peptides. As we enroll additional patients in this clinical trial, and perform deeper phenotyping of their tumor-reactive T cells, we will learn the determinants necessary for the successful generation of MTA-based vaccines, while informing future immunotherapeutic approaches and rational combinations. Clinical trial information: NCT02721043"

Clinical • IO biomarker • P1 data • Head and Neck Cancer • Hematological Malignancies • Oncology • Squamous Cell Carcinoma of Head and Neck

PGV-Prostate: The Safety and Tolerability of PGV001-based Personalized Multi-peptide Vaccines in the Adjuvant Setting. (clinicaltrials.gov) - P1; N=27; Recruiting; Sponsor: Ashutosh Kumar Tewari

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

"Adjuvant Neoantigen Peptide Vaccine PGV-001 Shows Promise in Multiple Malignancies @IcahnMountSinai @AACR #AAACR21 #lcsm #mmsm #bcsm #hncsm https://t.co/miJVoYwjdE" (@OncLive)

Clinical • Tumor-specific neoantigens • Breast Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Solid Tumor

Dr. Marron on the Population Included in a Phase 1 Study of PGV-001 Neoantigen Cancer Vaccine (OncLive) - "The trial enrolled patients who had at least a 30% chance of disease recurrence, which was based on factors such as tumor stage, and other histologic characteristics...For patients with multiple myeloma, it is almost guaranteed that they will experience recurrence following autologous stem cell transplant, he notes...Similarly high rates of recurrence have been observed in patients with recurrent head and neck cancer who are undergoing a second surgery, a population that comprised a notable portion of study participants (n = 6). Additionally, patients with advanced lung cancer experience similar higher rates of recurrence, Marron adds. Nearly all patients received an adjuvant therapy following treatment with surgery or transplant followed by PGV-001..."

Trial status • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Solid Tumor

Safety and Immunogenicity of Personalized Genomic Vaccine to Treat Malignancies (clinicaltrials.gov) - P1; N=13; Completed; Sponsor: Nina Bhardwaj; Active, not recruiting ➔ Completed; N=20 ➔ 13

Clinical • Enrollment change • Trial completion • Breast Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Serous Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Atezolizumab Given in Combination With a Personalized Vaccine in Patients With Urothelial Cancer (clinicaltrials.gov) - P1; N=15; Recruiting; Sponsor: Matthew Galsky; Trial completion date: Apr 2020 ➔ Jan 2022; Trial primary completion date: Apr 2020 ➔ Jan 2022

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Safety and Immunogenicity of Personalized Genomic Vaccine to Treat Malignancies (clinicaltrials.gov) - P1; N=20; Active, not recruiting; Sponsor: Nina Bhardwaj; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Atezolizumab Given in Combination With a Personalized Vaccine in Patients With Urothelial Cancer (clinicaltrials.gov) - P1; N=15; Recruiting; Sponsor: Matthew Galsky; Initiation date: Nov 2018 ➔ Mar 2019

Clinical • Combination therapy • Trial initiation date