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

Phase 1

Terminated

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

• Registration Number: NCT04348916
• Lead Sponsor: Oncorus, Inc.

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-04-13
• Study First Submitted QC: 2020-04-13
• Study First Posted: 2020-04-16
• Study Start: 2020-05-20
• Primary Completion: 2023-05-31
• Study Completion: 2023-05-31
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-06
• Last Update Posted: 2023-06-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 66

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose expansion of ONCR-177 and pembrolizumab in subjects with surface lesions	pembrolizumab	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
Dose expansion of ONCR-177 and pembrolizumab in subjects with liver metastases	pembrolizumab	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
Dose escalation of ONCR-177 by intratumoral injection in subjects with surface lesions	ONCR-177	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
Dose expansion of ONCR-177 by intratumoral injection in subjects with liver metastases	ONCR-177	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
Dose escalation of ONCR-177 by intratumoral injection in subjects with liver metastases	ONCR-177	Dose escalation of ONCR-177 intratumoral injections alone in four cohorts in subjects with advanced and/or refractory solid tumor cancer with liver metastases
Dose expansion of ONCR-177 in subjects with surface lesions	ONCR-177	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
Dose expansion of ONCR-177 and pembrolizumab in subjects with surface lesions	ONCR-177	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
Dose expansion of ONCR-177 and pembrolizumab in subjects with liver metastases	ONCR-177	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	40 Months	Duration of PFS for subjects
Durable Response Rate (DRR)	40 Months	DRR (continuous CR or PR ≥6 months)
Percentage of Objective Response Rate (ORR)	40 Months	Percentage of ORR
Incidence and rate of detection of ONCR-177	6 Months	Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of ONCR-177
Overall Survival (OS)	40 Months	OS rate for subjects
Changes in the level of HSV-1 antibodies compared to baseline	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

Trial Locations

Locations (11)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

The Ohio State University Wexner Medical Center James Cancer Hospital; 🇺🇸 Columbus, Ohio, United States

University Health Network, Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

City of Hope; 🇺🇸 Duarte, California, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Sarah Cannon Research Institute - Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

The University of Texas at Austin; 🇺🇸 Austin, Texas, United States