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

• ClinicalTrials.gov Identifier: NCT04348916
• Recruitment Status: Terminated
• First Posted: April 16, 2020
• Last Update Posted: June 8, 2023
• Sponsor: Oncorus, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Oncorus, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cancer; Melanoma; Solid Tumor; Squamous Cell Carcinoma of Head and Neck; Breast Cancer; Advanced Solid Tumor; Triple Negative Breast Cancer; Colorectal Carcinoma; Non-melanoma Skin Cancer; Liver Metastases	Biological: ONCR-177; Biological: pembrolizumab	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 20, 2020
• Actual Primary Completion Date: May 31, 2023
• Actual Study Completion Date: May 31, 2023

Arms and Interventions

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: MK-3475; KEYTRUDA
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: MK-3475; KEYTRUDA

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

City of Hope

Duarte, California, United States, 91010

United States, Colorado

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States, 80218

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

United States, Ohio

The Ohio State University Wexner Medical Center James Cancer Hospital

Columbus, Ohio, United States, 43210

United States, Tennessee

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Texas

The University of Texas at Austin

Austin, Texas, United States, 78701

Canada, Ontario

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Sponsors and Collaborators

Oncorus, Inc.

Merck Sharp & Dohme LLC

Investigators

• Study Director: John Goldberg, MD; Oncorus, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Oncorus, Inc.
• ClinicalTrials.gov Identifier: NCT04348916
• Other Study ID Numbers: ONCR-177-101; KEYNOTE-B73 ( Other Identifier: Merck Sharp & Dohme Corp )
• First Posted: April 16, 2020
• Last Update Posted: June 8, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Triple Negative Breast Neoplasms; Liver Neoplasms; Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms by Site; Breast Diseases; Skin Diseases; Carcinoma, Squamous Cell; Neoplastic Processes; Pathologic Processes; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors