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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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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

Intervention / Treatment
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* Biological: ONCR-177
* Biological: pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation of ONCR-177 by intratumoral injection in subjects with surface lesions<br>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<br>* Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1<br>|
| Experimental: Dose expansion of ONCR-177 in subjects with surface lesions<br>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<br>* Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1<br>|
| Experimental: Dose expansion of ONCR-177 and pembrolizumab in subjects with surface lesions<br>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<br>* Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1<br>Biological: pembrolizumab<br>* Anti-PD-1 monoclonal antibody<br>* Other names: KEYTRUDA;|
| Experimental: Dose escalation of ONCR-177 by intratumoral injection in subjects with liver metastases<br>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<br>* Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1<br>|
| Experimental: Dose expansion of ONCR-177 by intratumoral injection in subjects with liver metastases<br>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<br>* Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1<br>|
| Experimental: Dose expansion of ONCR-177 and pembrolizumab in subjects with liver metastases<br>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<br>* Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1<br>Biological: pembrolizumab<br>* Anti-PD-1 monoclonal antibody<br>* Other names: KEYTRUDA;|

What is the study measuring?
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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) |