PVX-410 / OncoPep - LARVOL DELTA

Early intervention in smoldering multiple myeloma: A systematic review of comparative prospective trials (ASH 2025) - "Two studies were phase I/II trials, one comparing the use of dose-escalated multipeptide PVX-410 vaccine +/- lenalidomide (R) in SMM patients, and the other comparing dose-escalated anakinra +/-Lenalidomide/dexamethasone (Rd)...Two studies were phase II RCTs; one compared Rd +/- Carfilzomib (K) in 58 high-risk SMM patients, with statistically significantly higher 3-year PFS in KRd of 94% versus Rd of 40%; p<0.001, across a median follow-up period of 34 months...The second phase II RCT included 20 intermediate- and high-risk SMM patients treated with Iberdomide (I) +/- d, with ORR of 84.6% versus 80% in the Id versus I group...One phase III RCT compared zoledronic acid +/- thalidomide in a total of 68 SMM patients, with a median TTP of 2.4 versus 1.2 years, 1-year PFS of 85% versus 55%, and 1-year ORR of 37% versus no confirmed response during the median follow-up of 5.9 years... Preliminary evidence from comparative trials suggests that early treatment of..."

Clinical • Review • Hematological Malignancies • Multiple Myeloma • Smoldering Multiple Myeloma

Immune Profiling and Responses of Smoldering Multiple Myeloma Patients Treated in a Phase Ib Study of Pvx-410 Vaccine Targeting XBP1/CD138/CS1 Antigens, and Citarinostat, a Histone Deacetylase Inhibitor (HDACi) with and without Lenalidomide (ASH 2023) - "There was one grade 3 trAE: specifically, a thromboembolic event in one patient who was receiving lenalidomide and despite aspirin prophylaxis, but who fully recovered. PB and marrow transcriptome profiling along with the immunogenicity studies are in progress and will be presented. We will evaluate whether PB mononuclear cells have the potential to replace BM as a surrogate for genetic and immunological surveillance in SMM, as we anticipate that further understanding of the immune alterations among patients with SMM and the response to immunomodulatory therapy may provide insight on early intervention and prevention of progression to symptomatic disease."

Clinical • Epigenetic controller • P1 data • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Smoldering Multiple Myeloma • CD8 • IFNG • IL2 • SDC1 • TNFA • XBP1

Early Versus Delayed Intervention in Smoldering Multiple Myeloma: A Meta-Analysis of Clinical Trials (ASH 2024) - "Trials were categorized by drug class : Melphalan-Prednisone (MP), Bisphosphonates (BP), Immunomodulatory drugs (IMD), Proteosome Inhibitors (PI), Monoclonal antibodies (MAB), PVX-410 multi-peptide vaccine (VC). Our study was limited by variability in risk stratification and response assessment methods across trials, and limited reporting of adverse effects. However, considering the overall reduction in progression and mortality, we recommend considering enrollment of patients with SMM into trials to help reinstate new therapeutic guidelines for SMM."

Retrospective data • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma • Thrombocytopenia • FCGR3A

PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Jun 2026 ➔ Dec 2027 | Trial primary completion date: Jul 2025 ➔ Dec 2026

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

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 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

Immune profiling of smoldering multiple myeloma patients treated in a phase lb study of PVX-410 vaccine targeting XBP1/CD138/CS1 antigens, and citarinostat, a histone deacetylase inhibitor (HDACi) with and without lenalidomide. (PubMed, Blood Cancer J) - No abstract available

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma • SDC1 • XBP1

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 2025 ➔ Sep 2026 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

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 | Phase classification: P1b ➔ P1 | Trial completion date: Jun 2023 ➔ Sep 2024 | Trial primary completion date: Jun 2023 ➔ Sep 2024

Epigenetic controller • Phase classification • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

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

Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Phase classification: P1b ➔ P1 | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

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 | Phase classification: P1b ➔ P1

Combination therapy • Phase classification • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

A phase 1b study of safety and immune response to PVX-410 vaccine alone and in combination with durvalumab (MEDI4736) in HLA-A2+ patients following adjuvant therapy for stage 2/3 triple negative breast cancer. (ASCO 2017) - P1b; "Pts will receive 6 doses of 800ug PVX (emulsified in Montanide (SC) and co-administered with Hiltonol (IM)) at 2-week intervals, and 2 doses of DUR 1500mg IV at the 4th and 6th vaccine visits. Additional correlative studies, including T-cell PD-1 and tissue PD-L1, XBP1, and CD138, are planned. Currently 4 pts are enrolled."

Checkpoint inhibition • Clinical • Combination therapy • P1 data • Biosimilar • Immunology • Multiple Myeloma • Triple Negative Breast Cancer

A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM (clinicaltrials.gov) - P1b | N=19 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: May 2022 ➔ Jun 2023 | Trial primary completion date: May 2022 ➔ Jun 2023

Enrollment closed • Epigenetic controller • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1b | N=20 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial primary completion date: Dec 2022 ➔ Jun 2023

Combination therapy • Metastases • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Adjuvant PVX-410 Vaccine and Durvalumab in Stage II/III Triple Negative Breast Cancer (clinicaltrials.gov) - P1b | N=22 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Sep 2022 ➔ Sep 2023 | Trial primary completion date: Dec 2021 ➔ Jun 2023

Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

A phase 1b study of PVX-410 vaccine in combination with pembrolizumab in metastatic triple negative breast cancer (mTNBC) (SABCS 2021) - P2 | "Both pembrolizumab and atezolizumab are FDA approved for programmed cell death ligand 1 positive (PDL1+) mTNBC...Pts received 6 doses of 800µg PVX emulsified in Montanide ISA 720 VG by subcutaneous injection co-administered with intramuscular Hiltonol weekly for 6 weeks (wks) followed by booster vaccine doses at wks 10 and 28, with concurrent intravenous 200 mg PEM every 3 wks starting with the second PVX dose...Clinical disease control was observed with a CBR of 31.6%. Based on these promising immune response results in this pretreated population, a phase 2 study with PVX+PEM in combination with standard chemotherapy in treatment naïve, PD-L1+ mTNBC is underway (NCT04634747)."

Combination therapy • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • IFNG • SDC1 • XBP1

OncoPep Completes $11 Million Series D Financing to Continue Clinical Trials and Advance Pipeline Development - "The Series D funding will enable OncoPep to continue its clinical trials and advance preclinical development of novel pipeline agents. OncoPep's lead investigational candidate, PVX-410, is a cancer vaccine in clinical development for smoldering multiple myeloma (SMM) and triple negative breast cancer (TNBC)."

Commercial • Breast Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Triple Negative Breast Cancer

A phase 1b study of PVX-410 (PVX) vaccine plus durvalumab (DUR) as adjuvant therapy in HLA-A2+ early stage triple negative breast cancer (eTNBC) to assess safety and immune response (SABCS 2019) - "Pts received 6 doses of 800ug PVX (subcutaneously) emulsified in Montanide and co-administered with Hiltonol (IM) every 2 weeks, and 2 doses of 1500mg DUR (IV) concurrent with the 4th and 6th vaccine treatments. Immune response data demonstrate that PVX induces antigen-specific T cell expansion and activation in these pts as observed by increases in PVX tetramer, IFN?, TNF?, IL-2 and CD137 positive T cells. These immune responses to PVX persisted for up to 6 months in most patients, indicating a prolonged immune response."

Clinical • P1 data • IL2

Phase 2 Study to Evaluate PVX-410 + Pembrolizumab + Chemotherapy for Metastatic, PD-L1+ Triple-Negative Breast Cancer (clinicaltrials.gov) - P2; N=53; Not yet recruiting; Sponsor: OncoPep, Inc.; Initiation date: Apr 2021 ➔ Nov 2021

Clinical • Trial initiation date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

Adjuvant PVX-410 Vaccine and Durvalumab in Stage II/III Triple Negative Breast Cancer (clinicaltrials.gov) - P1b; N=22; Active, not recruiting; Sponsor: Massachusetts General Hospital; Trial completion date: Feb 2022 ➔ Sep 2022; Trial primary completion date: Feb 2021 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1b; N=20; Active, not recruiting; Sponsor: Massachusetts General Hospital; Recruiting ➔ Active, not recruiting; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Combination therapy • Enrollment closed • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

A Study of PVX-410, a Cancer Vaccine, and Citarinostat +/- Lenalidomide for Smoldering MM (clinicaltrials.gov) - P1b; N=20; Recruiting; Sponsor: Massachusetts General Hospital; Trial completion date: May 2021 ➔ May 2022; Trial primary completion date: May 2021 ➔ May 2022

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

A Single-Arm, Open-Label, Multi-Center Phase II Study to Evaluate the Combination of PVX-410 + Pembrolizumab + Chemotherapy for Frontline Therapy of Metastatic, PD-L1+ Triple-Negative Breast Cancer (TNBC) in HLA-A2-Positive Patients (clinicaltrials.gov) - P2; N=53; Not yet recruiting; Sponsor: OncoPep, Inc.

Clinical • New P2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer