Study of ONCR-177 Alone and in Combination With PD-1 Blockade in Adult Subjects With Advanced and/or Refractory Cutaneous, Subcutaneous or Metastatic Nodal Solid Tumors or With Liver Metastases of Solid Tumors

A Phase 1, Open-Label, Multicenter, Dose Escalation and Expansion Study of ONCR-177, an Oncolytic Herpes Simplex Virus for Intratumoral Injection, Alone and in Combination With PD-1 Blockade in Adult Subjects With Advanced and/or Refractory Cutaneous, Subcutaneous or Metastatic Nodal Solid Tumors or With Liver Metastases of Solid Tumors

ONCR-177-101 is a phase 1, open-label, multi-center, dose escalation and expansion study of ONCR-177, an oncolytic Herpes Simplex Virus for intratumoral injection, alone and in combination with PD-1 blockade in adult subjects with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors or with Liver Metastases of Solid Tumors. The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Cancer; Breast Cancer; Solid Tumor; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Cancer; Advanced Solid Tumor; Liver Metastases; Colorectal Carcinoma; Non-melanoma Skin Cancer
• Intervention / Treatment: Biological: ONCR-177; Biological: pembrolizumab

Detailed Description

ONCR-177 is an intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1 (herpes simplex virus type 1) that selectively replicates in tumor tissue. Oncorus Inc. is developing ONCR-177 both as monotherapy and in combination with PD-1 blockade for the treatment of advanced solid tumor malignancies. This first-in-human (FIH) Phase 1 dose escalation and expansion study will determine the intratumoral dose of ONCR-177 as a monotherapy and in combination with pembrolizumab, in subjects with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors or with Liver Metastases of Solid Tumors. This protocol will enroll subjects who have at least one lesion that is visible, palpable or detectable and can be injected, and subjects who have liver metastases of solid tumors. Subjects with any cancer types who are eligible for the trial and have such lesions can be considered for enrollment. Additionally, preliminary evidence for clinical and immunologic activity will be sought to guide ongoing studies and development of ONCR-177 in subjects with cancers that are unmet medical needs. Confirmation of safety of ONCR-177 administration in combination with pembrolizumab will also be evaluated in this study, to enable development as part of combination immunotherapy.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network, Princess Margaret Cancer Centre
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center James Cancer Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78701
      • The University of Texas at Austin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female ≥ 18 years of age
• Solid tumor cancer with at least one injectable cutaneous, subcutaneous or nodal tumor OR at least one injectable liver metastasis that can be visualized and injected under radiologic guidance
• Have advanced or metastatic solid tumors who are refractory to, ineligible for, relapsed from and/or intolerant of standard of care treatment or must have a disease for which no standard of care exists
• Be fully recovered from major surgery and from the acute toxic effects of prior chemotherapy radiotherapy, or immunotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
• Must have adequate hematologic function in accordance with the study protocol
• Must have adequate hepatic function in accordance with the study protocol
• Must have adequate renal function in accordance with the study protocol
• Female subjects of reproductive potential must have a negative serum pregnancy test during Screening and a serum or urine pregnancy test must be re-confirmed as negative no more than 72 hours before starting study treatment. Females of reproductive potential as well as fertile men with partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use 2 effective forms of contraception (including at least 1 barrier form) from the time of giving informed consent, during the study, and for 6 months (both females and males) following the last dose of study drug(s)
• Life expectancy of ≥ 3 months

Expansion:

•Evaluable or measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria

Key Exclusion Criteria:

• Subjects on current antiviral treatment for herpes virus infections
• Requires chronic or intermittent treatment with systemic antivirals
• Any systemic anti-cancer treatment (including investigational agents) within 4 weeks prior to the first dose of study drug
• Has received prior radiotherapy within 2 weeks of start of study treatment
• Myelosuppressive chemotherapy within 4 weeks of study treatment
• Prior checkpoint inhibitor therapy administered within 4 weeks of study treatment
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has not fully recovered from any effects of major surgery or not free of significant detectable infection
• Other active malignancy within the previous 3 years of first dose of study treatment
• Has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis
• Have had significant active cardiac disease within 6 months prior to the start of study treatment
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
• Has received a live vaccine within 30 days prior to the first dose of study drug
• Are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation of ONCR-177 by intratumoral injection in subjects with surface lesions; Dose escalation of ONCR-177 intratumoral injections alone in four cohorts in subjects with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors	Biological: ONCR-177; Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1
Experimental: Dose expansion of ONCR-177 in subjects with surface lesions; Dose expansion of ONCR-177 intratumoral injections alone at the recommended phase 2 dose (RP2D) in subjects with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors	Biological: ONCR-177; Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1
Experimental: Dose expansion of ONCR-177 and pembrolizumab in subjects with surface lesions; Dose expansion of ONCR-177 intratumoral injections at the RP2D in combination with pembrolizumab in subjects with advanced and/or refractory cutaneous, subcutaneous or metastatic nodal solid tumors	Biological: ONCR-177; Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1; Biological: pembrolizumab; Anti-PD-1 monoclonal antibody; Other Names: KEYTRUDA; MK-3475
Experimental: Dose escalation of ONCR-177 by intratumoral injection in subjects with liver metastases; Dose escalation of ONCR-177 intratumoral injections alone in four cohorts in subjects with advanced and/or refractory solid tumor cancer with liver metastases	Biological: ONCR-177; Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1
Experimental: Dose expansion of ONCR-177 by intratumoral injection in subjects with liver metastases; Dose expansion of ONCR-177 intratumoral injections alone at the recommended phase 2 dose (RP2D) in subjects with advanced and/or refractory solid tumor cancer with liver metastases	Biological: ONCR-177; Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1
Experimental: Dose expansion of ONCR-177 and pembrolizumab in subjects with liver metastases; Dose expansion of ONCR-177 intratumoral injections at the RP2D in combination with pembrolizumab in subjects with advanced and/or refractory solid tumor cancer with liver metastases	Biological: ONCR-177; Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1; Biological: pembrolizumab; Anti-PD-1 monoclonal antibody; Other Names: KEYTRUDA; MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Dose-Limiting Toxicities (DLTs)	Percentage of subjects with DLTs	From Day 1 up to 30 days after last dose
Percentage of Adverse Events (AEs)	Percentage of subjects with AEs	From Day 1 up to 30 days after last dose
Percentage of Serious Adverse Events (SAEs)	Percentage of subjects with SAEs	From Day 1 up to 90 days after last dose
Maximum Tolerated Dose (MTD) of ONCR-177	MTD on the data collected during dose escalation	6 Months
Recommended Phase 2 Dose (RP2D) of ONCR-177	RP2D of ONCR-177 based on the data collected during dose escalation	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Objective Response Rate (ORR)	Percentage of ORR	40 Months
Durable Response Rate (DRR)	DRR (continuous CR or PR ≥6 months)	40 Months
Progression Free Survival (PFS)	Duration of PFS for subjects	40 Months
Overall Survival (OS)	OS rate for subjects	40 Months
Incidence and rate of detection of ONCR-177	Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of ONCR-177	6 Months
Changes in the level of HSV-1 antibodies compared to baseline	Change in HSV-1 antibody levels during treatment compared to baseline	From Day 1 up to last dose of ONCR-177 (up to 5 months)

Collaborators and Investigators

• Sponsor: Oncorus, Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: John Goldberg, MD, Oncorus, Inc.

Publications and helpful links

General Publications

• Haines BB, Denslow A, Grzesik P, Lee JS, Farkaly T, Hewett J, Wambua D, Kong L, Behera P, Jacques J, Goshert C, Ball M, Colthart A, Finer MH, Hayes MW, Feau S, Kennedy EM, Lerner L, Queva C. ONCR-177, an Oncolytic HSV-1 Designed to Potently Activate Systemic Antitumor Immunity. Cancer Immunol Res. 2021 Mar;9(3):291-308. doi: 10.1158/2326-6066.CIR-20-0609. Epub 2020 Dec 22.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2020
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 13, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Liver Diseases; Head and Neck Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Carcinoma, Squamous Cell; Neoplasms; Breast Neoplasms; Carcinoma; Colorectal Neoplasms; Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck; Liver Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: ONCR-177-101; KEYNOTE-B73 (Other Identifier: Merck Sharp & Dohme Corp)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No