Clinical trial NCT04348916: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Oncorus, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-04-16
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Dose-Limiting Toxicities (DLTs)
timeFrame: From Day 1 up to 30 days after last dose
measure: Percentage of Adverse Events (AEs)
timeFrame: From Day 1 up to 30 days after last dose
measure: Percentage of Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to 90 days after last dose
measure: Maximum Tolerated Dose (MTD) of ONCR-177
timeFrame: 6 Months
measure: Recommended Phase 2 Dose (RP2D) of ONCR-177
timeFrame: 6 Months
Secondary outcomes:
measure: Percentage of Objective Response Rate (ORR)
timeFrame: 40 Months
measure: Durable Response Rate (DRR)
timeFrame: 40 Months
measure: Progression Free Survival (PFS)
timeFrame: 40 Months
measure: Overall Survival (OS)
timeFrame: 40 Months
measure: Incidence and rate of detection of ONCR-177
timeFrame: 6 Months
measure: Changes in the level of HSV-1 antibodies compared to baseline
timeFrame: From Day 1 up to last dose of ONCR-177 (up to 5 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center James Cancer Hospital
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: The University of Texas at Austin
state: Texas
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Oncorus, Inc.
name: John Goldberg, MD
role: STUDY_DIRECTOR
References:
citation: 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.