Overview

This Phase 2, open-label, randomized study in non-small-cell lung cancer (NSCLC) is designed to evaluate the efficacy and safety of an intravenously delivered oncolytic vaccinia virus, Olvi-Vec, followed by platinum-doublet chemotherapy + Physician's Choice of Immune Checkpoint Inhibitor (ICI) vs. docetaxel for patients with advanced or metastatic NSCLC who have shown first disease progression (i.e., progressive disease not yet confirmed by further scan after initial scan showing progression) while on front-line treatment or maintenance ICI therapy after front-line treatment with platinum-doublet chemotherapy + ICI as standard of care.

Eligibility

Inclusion Criteria:

• Male or female 18 years or older.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.
• Have histologically or cytologically confirmed advanced or metastatic NSCLC.
• Histologically confirmed Stage III or IV squamous or nonsquamous [American Joint Committee on Cancer (AJCC) 8th edition].
• Received at least 2 cycles and maximum of 6 cycles of front-line platinum-based chemotherapy with ICI-based therapy, regardless of PD-L1 expression.
• Reached first disease progression by radiological assessment while receiving front-line or maintenance ICI.
• At least one measurable target tumor lesion anywhere except the brain per RECIST 1.1 by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan.
• Have adequate renal, hepatic, bone marrow function as well as adequate coagulation tests [International Normalized Ratio (INR)] and adequate immune function by lymphocyte count.
• Women of child-bearing potential must have a negative serum pregnancy test prior to initiating study dosing.
• Be willing and able to comply with scheduled visits, the treatment plan, imaging and laboratory tests.

Exclusion Criteria:

• Active and untreated urinary tract infection, pneumonia, or other systemic infections.
• Current symptomatic central nervous system (CNS) metastasis.
• Any uncontrolled systemic disease, condition or comorbidity that, in the opinion of the Investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
• Persistent toxicities [Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3] caused by previous anticancer therapy; alopecia and vitiligo are excluded toxicities.
• Required the use of additional immunosuppression other than corticosteroids for the management of an adverse event or have experienced recurrence of an adverse event if re-challenged, or currently require maintenance doses of >10 mg prednisone or equivalent per day.
• Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, tecovirimat, or other agents with known anti-vaccinia activities).
• Underwent major surgery within 4 weeks, or have insufficient recovery from surgical-related trauma or wound healing, prior to the planned first dose of treatment in either Arm.
• Have received prior virus-based gene therapy or therapy with cytolytic virus of any type.
• Vaccination against smallpox or monkeypox within 1 year of study therapy.
• Any non-oncology vaccine therapy used for prevention of infectious diseases, such as seasonal (influenza) vaccinations, corona virus disease (COVID) vaccination or other vaccines, within 2 weeks of the planned first dose of study drug.
• Clinically significant skin disease as assessed by the Investigator (e.g., severe eczema, psoriasis, or any unresolved skin injury or ulcer).
• Known hypersensitivity to carboplatin, cisplatin, paclitaxel or nab-paclitaxel, docetaxel, or any of the constituents of Olvi-Vec (i.e., gentamicin).
• Had severe hypersensitivity (CTCAE Grade ≥ 3) to ICI and/or any of its excipients previously.
• Dementia or altered mental status that would prohibit informed consent, and/or psychiatric illness/social situations that might interfere or limit compliance with study requirements.