Advanced Solid Tumor, Breast Cancer, Cancer, Colorectal Carcinoma, Liver Metastases, Melanoma, Non-melanoma Skin Cancer, Solid Tumor, Squamous Cell Carcinoma of Head and Neck, Triple Negative Breast Cancer
Conditions
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.
Interventions
BIOLOGICALONCR-177
Intratumorally administered oncolytic immunotherapy comprised of a genetically engineered HSV-1
BIOLOGICALpembrolizumab
Anti-PD-1 monoclonal antibody
Sponsors
Merck Sharp & Dohme LLC
Oncorus, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Objective Response Rate (ORR) | 40 Months | Percentage of ORR |
| 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 |
| 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 |
Countries
Canada, United States
Outcome results
None listed