A Phase 1 Study of OTS-412 (Recombinant Oncolytic Vaccinia Virus) in Treatment-refractory Solid Tumor Patients

NCT07170592 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OTS412-101
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical trial aims to determine whether the administration of the investigational drug OTS-412, OTS-412 in combination with hydroxyurea or hydroxyurea/atezolizumab is safe and effective for patients with various types of cancer.

Conditions

Treatment-Refractory Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of adverse events (AEs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 or higher in OTS 412, OTS-412/HU combination, and OTS 412/HU/atezolizumab combination treatment

  From enrollment to 180 days after the last dose of the study drugs.

Secondary Outcomes (12)

• Tumor response, as determined by the Investigator according to RECIST v1.1 (or mRECIST for hepatocellular carcinoma) and/or iRECIST

  From enrollment to 28 days after the last dose of the study drugs

• Overall survival defined as time from the study drug initiation to death from any cause

  From enrollment up to 15 years after end of study

• PK analysis: Assessment of the concentration of OTS-412 genomic particles (qPCR) in blood over time

  From enrollment to Cycle 2 Day 1(each cycle is 21 days)

• Rate of patients to achieve target absolute neutrophil count (ANC) level (between 1500 and 3000/μL) 7 days after OTS-412 administration

  7 days after OTS-412 administration

• Changes in ANC over time

  From enrollment to 180 days after the last dose of the study drugs.

Other Outcomes (1)

• Changes in activated neutrophils (aN) and activated T lymphocytes (aT) assessed by FLuc activity in isolated neutrophils and T lymphocytes over time (Korean sites only)

  From enrollment to 6 weeks after first study drug administration

Study Arms (6)

Cohort 1

EXPERIMENTAL

OTS412 3 \* 10E8 pfu + HU 15 \~ 20mg/kg/day

Drug: OTS-412; Drug: Hydroxyurea (HU)

Cohort 2

EXPERIMENTAL

OTS412 3 \* 10E8 pfu + HU 25 \~ 30mg/kg/day

Drug: OTS-412; Drug: Hydroxyurea (HU)

Cohort 3

EXPERIMENTAL

OTS412 3 \* 10E8 pfu + HU 35mg/kg/day

Drug: OTS-412; Drug: Hydroxyurea (HU)

Cohort 4

EXPERIMENTAL

OTS412 3 \* 10E8 pfu + HU optimal dose + Atezolizumab 1200mg

Drug: Atezolizumab; Drug: OTS-412; Drug: Hydroxyurea (HU)

Cohort 5

EXPERIMENTAL

OTS412 1 \* 10E8 pfu + HU optimal dose + Atezolizumab 1200mg

Drug: Atezolizumab; Drug: OTS-412; Drug: Hydroxyurea (HU)

Expansion cohort

EXPERIMENTAL

OTS412 optimal dose + HU optimal dose + Atezolizumab 1200mg

Drug: Atezolizumab; Drug: OTS-412; Drug: Hydroxyurea (HU)

Interventions

OTS-412 DRUG

3×10E8 pfu, once q3 weeks, 3 cycles, IT

Cohort 1

Hydroxyurea (HU) DRUG

15 mg/kg/day, 14 days, 1 cycle, PO

Cohort 1

Atezolizumab DRUG

1,200 mg, once q3 weeks, 2 cycles, IV

Cohort 4; Cohort 5; Expansion cohort

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Diagnosed with a malignant solid tumor via histology or cytology, although a radiological diagnosis is permissible for hepatocellular carcinoma
• Solid tumors that demonstrate limited response or resistant to SOC therapy, particularly when atezolizumab or other PD-L1 inhibitors, or PD-1 inhibitors are administered as monotherapy or in combination therapy. This may include, but not limited to, hepatocellular carcinoma, melanoma, renal cell carcinoma, urothelial carcinoma, biliary cancer, head and neck cancer, gastric cancer, breast cancer, colorectal cancer, and any solid tumor with microsatellite instability (MSI)-high status. At minimum, SOC treatment presented in the Protocol should have been received for each cancer type.
• Patients with tumors that have known actionable molecular alterations (i.e. EGFR, ALK, BRAF, etc) must have progressed on targeted therapy.
• Lesions that are deemed feasible for injection either directly (palpable subcutaneous tumors) or under ultrasound guidance (deep-seated tumors). Additionally, tumor(s) should not be adjacent or encasing vital structures such as major nerves or blood vessels, pericardium, gastrointestinal tract or other hollow organs, mucosal regions or spinal cord that could cause occlusion or compression in case of tumor swelling or erosion and major bleeding in the case of necrosis.
• At least one measurable (longest diameter, LD ≥1 cm) and injectable tumor that has not been previously received local treatment on computed tomography (CT) or magnetic resonance imaging (MRI)
• The total volume of injectable tumor(s) should be 2 cm3 or more in 1x10E8 pfu dosing cohorts and 6 cm3 or more in 3x10E8 pfu dosing cohorts.
• Life expectancy of 12 weeks or more
• Eastern cooperative oncology group (ECOG) performance status is 0, 1, or 2
• Adequate pulmonary function, such as baseline pulse oximetry of at least 92% on room air
• Laboratory test results meet the following:
• ANC ≥ 1,500 /μL
• White blood cell (WBC) ≥ 2,500 /μL
• Hemoglobin (Hb) ≥ 9.0 g/dL without packed red blood cell transfusion within the prior 2 weeks
• Platelet ≥ 75,000 /μL without platelet transfusion

You may not qualify if:

• Patients who have previously received talimogene laherparepvec (Imlygic) or any other oncolytic virus, have received any systemic or local anti-cancer therapy for tumors within 4 weeks prior to the first administration of the study drugs(C1D1), or have not recovered from the adverse events due to these therapies to at least Grade 1 severity or returned to baseline levels prior to C1D1, with the exceptions of any grade of alopecia and Grade 2 neuropathy.
• Patients who have untreated symptomatic brain metastases, have treated brain metastases without evidence of stability or improvement on two scans at least two weeks apart, have leptomeningeal disease regardless of treatment, or have received anti-convulsants within the last 28 days.
• Tumors adjacent to vital neurovascular structures or at risk of airway compromise in the event of post injection tumor swelling, bleeding, or inflammation. Patients with tumors near vital structures can be enrolled as long as they have other lesions that are appropriate for injection (these tumors near vital structures will not be injected).
• History of other malignancies that developed within 5 years (However, cervical carcinoma in situ, basal cell carcinoma, or squamous cell skin cancer, and all cancers after 5 years since it was cured are acceptable.)
• History of organ transplant surgery
• Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose systemic corticosteroids (prednisone 20 mg/day or equivalent which is ongoing and/or was taken more than 4 weeks within the preceding 2 months of study treatment)
• History of or active autoimmune disease
• Ongoing severe inflammatory skin disease (as determined by the Investigator) requiring medical treatment or history of severe eczema (as determined by the Investigator) requiring prior medical treatment
• Anticoagulation or anti-platelet medication that cannot be withheld for the required period prior to and after the OTS-412 injection, specifically:
• Coumadin for 7 days
• Direct Factor Xa inhibitor (rivaroxaban, apixaban, edoxaban) for 4 days
• Oral direct thrombin inhibitor (dabigatran) for 4 days
• Aspirin, clopidogrel, ticagrelor for 7 days
• Prasugrel for 9 days
• Low molecular weight heparin for 24 hours

Sponsors & Collaborators

• Bionoxx Inc.: lead

MeSH Terms

Interventions

Hydroxyurea; atezolizumab

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Central Study Contacts

Younok Choi, Team Manager

CONTACT

+82-55-367-7457; yochoi@bionoxx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: September 12, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 29, 2025

Record last verified: 2025-07