Efficacy & Safety of Olvimulogene Nanivacirepvec & Platinum-doublet + Physician's Choice of Immune Checkpoint Inhibitor Compared to Docetaxel in NSCL Cancer

Prior treatment

• 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.
• Had severe hypersensitivity (CTCAE Grade ≥ 3) to ICI and/or any of its excipients previously.

Other illness

• Active and untreated urinary tract infection, pneumonia, or other systemic infections.
• 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.
• 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).
• 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.

Other

• Current symptomatic central nervous system (CNS) metastasis.

• 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.