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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04348916
• Other study ID #: ONCR-177-101
• Secondary ID: KEYNOTE-B73
• Status: Terminated
• Phase: Phase 1
• Start date: May 20, 2020
• Est. completion date: May 31, 2023

Study information

• Verified date: June 2023
• Source: Oncorus, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: May 31, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Cancer
• Breast Neoplasms
• Cancer
• Carcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Liver Metastases
• Liver Neoplasms
• Melanoma
• Neoplasm Metastasis
• Neoplasms
• Non-melanoma Skin Cancer
• Solid Tumor
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• ONCR-177
Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1
• pembrolizumab
Anti-PD-1 monoclonal antibody

Locations

Country	Name	City	State
Canada	University Health Network, Princess Margaret Cancer Centre	Toronto	Ontario
United States	Emory University	Atlanta	Georgia
United States	The University of Texas at Austin	Austin	Texas
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	The Ohio State University Wexner Medical Center James Cancer Hospital	Columbus	Ohio
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Sarah Cannon Research Institute - Tennessee Oncology	Nashville	Tennessee
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Oncorus, Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Dose-Limiting Toxicities (DLTs)	Percentage of subjects with DLTs	From Day 1 up to 30 days after last dose
Primary	Percentage of Adverse Events (AEs)	Percentage of subjects with AEs	From Day 1 up to 30 days after last dose
Primary	Percentage of Serious Adverse Events (SAEs)	Percentage of subjects with SAEs	From Day 1 up to 90 days after last dose
Primary	Maximum Tolerated Dose (MTD) of ONCR-177	MTD on the data collected during dose escalation	6 Months
Primary	Recommended Phase 2 Dose (RP2D) of ONCR-177	RP2D of ONCR-177 based on the data collected during dose escalation	6 Months
Secondary	Percentage of Objective Response Rate (ORR)	Percentage of ORR	40 Months
Secondary	Durable Response Rate (DRR)	DRR (continuous CR or PR =6 months)	40 Months
Secondary	Progression Free Survival (PFS)	Duration of PFS for subjects	40 Months
Secondary	Overall Survival (OS)	OS rate for subjects	40 Months
Secondary	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
Secondary	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)