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

Sponsor

Oncorus, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04348916

Collaborator

Merck Sharp & Dohme LLC (Industry)

132

Enrollment

Locations

Arms

97.4

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

132 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

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jul 1, 2028

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

Percentage of Dose-Limiting Toxicities (DLTs) [From Day 1 up to 30 days after last dose]
Percentage of subjects with DLTs
Percentage of Adverse Events (AEs) [From Day 1 up to 30 days after last dose]
Percentage of subjects with AEs
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
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

Percentage of Objective Response Rate (ORR) [40 Months]
Percentage of ORR
Durable Response Rate (DRR) [40 Months]
DRR (continuous CR or PR ≥6 months)
Progression Free Survival (PFS) [40 Months]
Duration of PFS for subjects
Overall Survival (OS) [40 Months]
OS rate for subjects
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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