MV-NIS / Vyriad - LARVOL DELTA

MV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer (clinicaltrials.gov) - P1/2 | N=34 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: Dec 2025 ➔ Sep 2026

Trial completion date • Fallopian Tube Cancer • Infectious Disease • Measles • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • CD4

MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer (clinicaltrials.gov) - P2 | N=17 | Terminated | Sponsor: Mayo Clinic | N=66 ➔ 17 | Active, not recruiting ➔ Terminated | Active, not recruiting ➔ Terminated; poor accrual

Enrollment change • Platinum resistant • Trial termination • Carcinosarcoma • Fallopian Tube Cancer • Infectious Disease • Measles • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Sarcoma • Solid Tumor • Urothelial Cancer

Measles oncolytic virus as an immunotherapy for recurrent/refractory pediatric medulloblastoma and atypical teratoid rhabdoid tumor: results from PNOC005. (PubMed, Clin Cancer Res) - "This is the first trial investigating intratumoral as well as repeated intrathecal delivery of MV-NIS in children with MB and ATRT. We show that therapy is safe and well-tolerated with minimal adverse effects. Immune markers and biologic correlates preliminarily indicate anti-viral effects in tumors."

IO biomarker • Journal • Brain Cancer • Infectious Disease • Measles • Medulloblastoma • Oncology • Pediatrics • Rhabdoid Tumor • Sarcoma • Solid Tumor

Phase I/II Trial of Adipose Tissue Derived Mesenchymal Stem Cell Delivery of a Measles Virus Strain Engineered to Express the Sodium Iodine Symporter (MV-NIS) in Ovarian Cancer Patients (ASGCT 2025) - "Adipose tissue derived mesenchymal stem cells can safely deliver measles virus strains engineered to express sodium iodine symporter gene without dose limiting toxicity being encountered. This form of cell-based virus delivery led to efficacy that was significantly better than virus alone or contemporary data on standard of care treatments in pretreated recurrent ovarian cancer and to the development of antitumor cellular and humoral immune responses. Further clinical development is warranted."

Clinical • P1/2 data • Hematological Disorders • Infectious Disease • Measles • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • CD46 • FOLR1 • HER-2 • IFNG • IGFBP2 • IL17A • IL4 • MUC16 • NECTIN4

NEOADJUVANT INTRAVESICAL ONCOLYTIC MEASLES IMMUNOTHERAPY FOR BLADDER CANCER (AUA 2025) - "Herein we describe the results of a clinical study evaluating safety and immunogenicity of neoadjuvant intravesical MV-NIS administration in patients with high grade bladder cancer patients prior to radical cystectomy... Intravesical oncolytic measles virus therapy exhibits a remarkable safety profile and promising efficacy. Correlative studies show that oncolytic MV can infect bladder tumor cells and is potently immunogenic. The rate of post-treatment tumor downstaging and pT0 pathology provide compelling evidence of the potential clinical utility of intravesical MV therapy for BCG unresponsive NMIBC."

Clinical • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Measles • Oncology • Solid Tumor • CD20 • CD4 • CD46

MV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer (clinicaltrials.gov) - P1/2 | N=34 | Active, not recruiting | Sponsor: Mayo Clinic | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2024

Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Infectious Disease • Measles • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • CD4

MC1372: Vaccine Therapy in Treating Patients with Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Mayo Clinic | Recruiting ➔ Completed | N=30 ➔ 9 | Trial completion date: Sep 2024 ➔ Apr 2024 | Trial primary completion date: Sep 2024 ➔ Apr 2024

Enrollment change • Surgery • Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • Genetic Disorders • Infectious Disease • Measles • Neurofibromatosis • Neurofibrosarcoma • Oncology • Solid Tumor

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures. (PubMed, EBioMedicine) - "Considering the heterogeneity of PDAC and the complexity of biological therapies such as OVs, no single biomarker can explain the spectrum of response patterns. For selection of a particular OV, PDAC molecular subtype, ISG expression as well as activation of distinct signaling and metabolic pathways should be considered. Combination therapies can overcome resistance in specific constellations. Overall, oncolytic virotherapy is a viable treatment option for PDAC, which warrants further development. This study highlights the need for personalised treatment in OVT. By providing all primary data, this study provides a rich source and guidance for ongoing developments."

IO biomarker • Journal • Oncolytic virus • Gastrointestinal Cancer • Hepatology • Infectious Disease • Measles • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CGAS • LGALS1

MV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer (clinicaltrials.gov) - P1/2 | N=34 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting | N=57 ➔ 34

Enrollment change • Enrollment closed • Fallopian Tube Cancer • Infectious Disease • Measles • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • CD4

MV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer (clinicaltrials.gov) - P1/2 | N=57 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Infectious Disease • Measles • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • CD4

Oncolytic virotherapies for pediatric tumors. (PubMed, Expert Opin Biol Ther) - "We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future."

Journal • Oncolytic virus • Review • Herpes Simplex • Infectious Disease • Measles • Oncology • Pediatrics • Solid Tumor

Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Dec 2023 ➔ Sep 2024 | Trial primary completion date: Jun 2023 ➔ Sep 2024

Surgery • Trial completion date • Trial primary completion date • Brain Cancer • Fibrosis • Genetic Disorders • Infectious Disease • Measles • Neurofibromatosis • Neurofibrosarcoma • Oncology • Solid Tumor

MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer (clinicaltrials.gov) - P1/2 | N=57 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Endometrial Adenocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Infectious Disease • Measles • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Solid Tumor • CD4 • CEACAM5

Trial of Intravesical Measles Virotherapy in Patients With Bladder Cancer Who Are Undergoing Radical Cystectomy (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Vyriad, Inc. | Active, not recruiting ➔ Completed

Trial completion • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Measles • Oncology • Solid Tumor • Urothelial Cancer

Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Sabine Mueller, MD, PhD | Recruiting ➔ Completed | Trial completion date: May 2024 ➔ May 2023 | Trial primary completion date: Dec 2023 ➔ May 2023

Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • Infectious Disease • Medulloblastoma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • CD4

Trial of Intravesical Measles Virotherapy in Patients With Bladder Cancer Who Are Undergoing Radical Cystectomy (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Vyriad, Inc. | Recruiting ➔ Active, not recruiting | N=16 ➔ 8 | Trial completion date: Dec 2022 ➔ May 2023 | Trial primary completion date: Apr 2022 ➔ May 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Oncology • Solid Tumor • Urothelial Cancer

MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer (clinicaltrials.gov) - P2 | N=66 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting

Enrollment closed • Endometrial Adenocarcinoma • Endometrial Cancer • Fallopian Tube Cancer • Infectious Disease • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Sarcoma • Solid Tumor

Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Mayo Clinic | Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial primary completion date • Brain Cancer • Fibrosis • Genetic Disorders • Infectious Disease • Neurofibromatosis • Neurofibrosarcoma • Oncology • Solid Tumor

[VIRTUAL] Safety and efficacy of neoadjuvant intravesical oncolytic MV-NIS in patients with Urothelial carcinoma (AACR-NCI-EORTC 2021) - No abstract available

Clinical • Oncology • Solid Tumor • Urothelial Cancer

Viral Therapy In Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer or Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Infectious Disease • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ER • HER-2 • PGR

Therapeutic Applications for Oncolytic Self-Replicating RNA Viruses. (PubMed, Int J Mol Sci) - "Multiple myeloma patients treated with an oncolytic measles virus (MV-NIS) resulted in increased T-cell responses against the measles virus and several tumor-associated antigen responses and complete remission in one patient. Furthermore, MV-CEA administration to patients with ovarian cancer resulted in a stable disease and more than doubled the median overall survival."

IO biomarker • Journal • Review • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Ovarian Cancer • Solid Tumor

Safety and efficacy of neoadjuvant intravesical oncolytic MV-NIS in patients with urothelial carcinoma (SITC 2021) - P1 | "MV-NIS induced inflammation may act synergistically with checkpoint blockade therapies. Trial Registration NCT03171493"

Clinical • Bladder Cancer • Oncology • Solid Tumor • Urothelial Cancer

Safety and efficacy of neoadjuvant intravesical oncolytic MV-NIS in patients with urothelial carcinoma. (ASCO-GU 2022) - P1 | "The higher-than-expected rate of tumor downstaging and pT0 pathology, paired with the significant immune infiltrate observed in post-treatment bladder tissue, provide compelling evidence that intravesical MV-NIS has clinical activity against UC. These results support the use of two doses of ̃1x109 TCID50 as the RP2D in future clinical studies for BCG unresponsive NMIBC or MIBC patients. MV-NIS induced inflammation may act synergistically with checkpoint blockade therapies."

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Jun 2022 ➔ Dec 2023 | Trial primary completion date: Jun 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Brain Cancer • Fibrosis • Genetic Disorders • Infectious Disease • Neurofibromatosis • Neurofibrosarcoma • Oncology • Solid Tumor

Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT (clinicaltrials.gov) - P1 | N=46 | Recruiting | Sponsor: Sabine Mueller, MD, PhD | Trial completion date: May 2023 ➔ May 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Brain Cancer • Infectious Disease • Medulloblastoma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • CD4