p53MVA / Tara I-O, City of Hope - LARVOL DELTA

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jun 2025 ➔ May 2026

Platinum resistant • Trial completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MUC16 • PD-L1 • TP53

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ Oct 2025

Trial completion date • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Rectal Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • MSI • TP53

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MUC16 • PD-L1 • TP53

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Aug 2024 ➔ Dec 2024

Trial completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MUC16 • PD-L1 • TP53

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2024 ➔ Aug 2024

Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MUC16 • PD-L1 • TP53

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Trial completion date • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Rectal Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • MSI • TP53

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MUC16 • PD-L1 • TP53

Immunologic Signatures of Peripheral Blood T Cells Reveal the Outcome of p53MVA Vaccine and Pembrolizumab Treatment in Patients with Advanced Ovarian Cancer. (PubMed, Cancer Res Commun) - "p53MVA/pembrolizumab immunotherapy showed promising anti-tumor activity in patients who demonstrated functionally competent peripheral blood T cells. Detection of markers of terminally differentiated T cells before treatment may identify patients unlikely to respond to p53MVA/pembrolizumab."

IO biomarker • Journal • Metastases • Oncology • Ovarian Cancer • Solid Tumor

Immunologic Signatures of Peripheral Blood T Cells Reveal the Outcome of p53MVA Vaccine and Pembrolizumab Treatment in Patients with Advanced Ovarian Cancer (Cancer Res Commun) - P2 | N=29 | NCT03113487 | "We observed 6/28 (21%) patients with a clinical benefit to therapy, including 3 partial responses (PR) and 3 patients with stable disease (SD) for 6+ months. The median progression-free survival (PFS) was 1.8 months (95% CI 1.7-3.8) and median overall survival (OS) was 15.1 months (9.4-30.4). Two patients remain progression-free at 28 and 33 months. Of the 18 patients evaluable in correlative studies, 6 were immunological responders of whom 5 had clinical benefit (3 PR, 2 SD)....p53MVA/pembrolizumab immunotherapy showed promising anti-tumor activity in patients who demonstrated functionally competent peripheral blood T cells."

P2 data • Ovarian Cancer

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: City of Hope Medical Center | N=19 ➔ 11 | Trial completion date: Dec 2022 ➔ Dec 2023

Combination therapy • Enrollment change • Trial completion date • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Rectal Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • MSI • PD-1 • TP53

A phase 1 study of p53MVA vaccine in combination with pembrolizumab. (ASCO-SITC 2018) - P1; "Targeting p53 antigen associated with cancer using a viral vaccine p53MVA in combination with PD-1 blockade represents a novel immunotherapeutic approach capable of stimulating systemic immune responses and associated clinical benefit."

Combination therapy • P1 data • Colorectal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Melanoma • Non Small Cell Lung Cancer • Sarcoma • Triple Negative Breast Cancer

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: City of Hope Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CD8 • MUC16 • PD-1 • PD-L1 • TP53

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2021 ➔ Dec 2022

Combination therapy • Trial completion date • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Rectal Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • MSI • PD-1 • TP53

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jan 2022 ➔ Dec 2023 | Trial primary completion date: Jan 2022 ➔ Dec 2023

IO biomarker • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CD8 • MUC16 • PD-1 • PD-L1 • TP53

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy (clinicaltrials.gov) - P1; N=19; Active, not recruiting; Sponsor: City of Hope Medical Center; Trial completion date: Feb 2020 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Rectal Cancer • Renal Cell Carcinoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • MSI • PD-1 • TP53

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: City of Hope Medical Center; Trial completion date: Jan 2021 ➔ Jan 2022; Trial primary completion date: Jan 2021 ➔ Jan 2022

Clinical • IO biomarker • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: City of Hope Medical Center; Trial completion date: Feb 2020 ➔ Feb 2021; Trial primary completion date: Feb 2020 ➔ Feb 2021

Trial completion date • Trial primary completion date • PD-L1

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2; N=28; Not yet recruiting; Sponsor: City of Hope Medical Center

Clinical • IO Biomarker • New P2 trial

P53MVA and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: City of Hope Medical Center; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • IO Biomarker

p53-reactive T cells are associated with clinical benefit in patients with platinum-resistant epithelial ovarian cancer after treatment with a p53 vaccine and gemcitabine chemotherapy. (PubMed, Clin Cancer Res) - "p53MVA was well tolerated, but gemcitabine without steroid pre-treatment was intolerable in some patients. However, elevated p53-reactive CD4+ and CD8+T cell responses post therapy correlated with longer PFS. Therefore, if responses to p53MVA could be enhanced with alternative agents, superior clinical responses may be achievable."

Clinical • Journal

Evaluation of safety and efficacy of p53MVA vaccine combined with pembrolizumab in patients with advanced solid cancers. (PubMed, Clin Transl Oncol) - "We have shown that the combination of p53MVA vaccine with pembrolizumab is feasible, safe, and may offer clinical benefit in select group of patients that should be identified through further studies."

Clinical • IO Biomarker • Journal • PD(L)-1 Biomarker

Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy (clinicaltrials.gov) - P1; N=19; Active, not recruiting; Sponsor: City of Hope Medical Center; Trial completion date: Feb 2019 ➔ Feb 2020; Trial primary completion date: Feb 2019 ➔ Feb 2020

Clinical • Combination therapy • PD(L)-1 Biomarker • Trial completion date • Trial primary completion date