Study to Assess the Safety and Preliminary Efficacy of STI-1386 Oncolytic Virus in Relapsed or Refractory Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1b study to assess the safety and tolerability of STI-1386, an oncolytic virus, in subjects with relapsed and refractory solid tumors (RRSTs).

Detailed Description
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This is a Phase 1b, dose-ascending study to assess the safety, tolerability and recommended phase 2 dose (RP2D) of STI-1386 in subjects with relapsed and refractory solid tumors (RRSTs). STI-1386 is a second generation oncolytic virus. This is a two-stage study, the first stage uses a single ascending dose, followed by the multiple ascending dose stage.

Official Title
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A Phase 1b, Dose-Escalation Study of the Safety and Preliminary Efficacy of STI-1386 Oncolytic Virus in Patients With Relapsed or Refractory Solid Tumors

Conditions
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Cancer, Cancer of Pancreas, Sarcoma, Hepatic Metastasis, Solid Tumor

Intervention / Treatment
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* Drug: STI-1386


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed extracranial solid tumors that are relapsing or refractory including locally advanced pancreatic cancer, unresectable soft tissue sarcomas, hepatic metastases due to colorectal cancer At least one measurable disease per Response Evaluation Criteria in Solid Tumors v. 1.1 (RECIST 1.1) with a non-nodal lesion with longest diameter ≥ 10 mm or nodal lesions with short diameter ≥ 15 mm Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 As assessed by the investigator, ≥ 3 month life expectancy Adequate hematologic, liver and renal function at Screening as determined by lab criteria Recovered < Grade 2 from all acute toxicities from previous therapy Has not had prior treatment with high dose corticosteroids within the 2 weeks of screening Is willing and able to comply with the study schedule and other protocol requirements Willing to follow contraception guidelines Exclusion Criteria: Have a primary brain tumor Use of an investigational drug or local therapy or agent within 2 weeks of first dose of study drug. Current systemic chemotherapy per investigator's discretion is allowed, but no immune checkpoint inhibitors or immune modulators Use of anticoagulants or anti-platelet agents unless subject can safely start/stop to allow intratumoral injections Use of bevacizumab (Avastin) within 28 days of the STI-1386 injection Diagnosis of other malignancies that have required therapy in the last year or are not in complete remission. Exceptions include non-metastatic basal cell or squamous cell carcinomas of the skin, prostate cancer or cancer in situ that does not require treatment currently or is otherwise under control Requiring chronic systemic immunosuppressants, including steroids > 20 mg/day Presence of bulky disease defined as any single mass > 5 cm in greatest dimension will trigger a discussion to determine eligibility New York Heart Association (NYHA) Class >3 of left ventricular ejection fraction (LVEF) < 50% Prolonged corrected QT interval as determined by 12-lead electrocardiogram Has spinal cord compression or clinically unstable brain metastases within 4 weeks of first dose of study drug Evidence of active herpes infection and/or chronic herpes infection requiring prophylactic antiviral medication that may not be discontinued Has an active or recent COVID-19 infection, must have a negative RT-PCR test and not have had symptoms within 4 weeks of day 1 of study drug administration Any active infection requiring systemic therapy within 72 hours of injection of STI-1386, excluding anti-viral maintenance therapy for HIV Moderate to severe chronic obstructive pulmonary disease or other moderate to severe chronic respiratory conditions unless under treatment and stable for the 3 months of screening Have active human immunodeficiency virus (HIV) infection, human T-cell leukemia virus type 1 (HTLV1) infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia Pregnant or lactating or up to 3 months post last dose Underlying medical conditions that, in the opinion of the investigator and/or medical monitor will prevent the subject from participating Allergy to acyclovir and related anti-HSV antiviral agents

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STI-1386<br>A dose-escalation standard 3+3 design will be utilized and a total of 3 dosing cohorts are planned, receiving up to 4 mL of 1 x 10^6 / 1 mL, 1 x 10^7 / 1 mL, or 1 x 10^8 / 1 mL. | Drug: STI-1386<br>* Second generation oncolytic virus<br>* Other names: Seprehvec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) | Safety as assessed by incidence of AEs by type, frequency, severity, and causality using the Common Terminology Criteria for Adverse Events, Version 5 (CTCAEv5) | baseline through study completion at up to approximately 29 months | 
| Incidence of immune-related adverse events (IrAEs) | Safety as assessed by incidence of IrAEs by type, frequency, severity, and causality using the Common Terminology Criteria for Adverse Events, Version 5 (CTCAEv5) | baseline through study completion at up to approximately 29 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary Efficacy of STI-1386 | Assess the preliminary efficacy of STI-1386 using the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) | baseline through study completion at up to approximately 29 months | 
| Measuring Pharmacokinetic [PK] Profile | STI-1386 blood plasma concentrations will be measured | baseline through study completion at up to approximately 29 months | 
| Assess immunoglobulin levels | Assessment of serum immunoglobulin levels | baseline through study completion at up to approximately 29 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, solid tumor, hepatic metastasis