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

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 JointCommittee on Cancer (AJCC) 8th edition].

• Received at least 2 cycles and maximum of 6 cycles of front-line platinum-basedchemotherapy with ICI-based therapy, regardless of PD-L1 expression.

• Reached first disease progression by radiological assessment while receivingfront-line or maintenance ICI.

• At least one measurable target tumor lesion anywhere except the brain per RECIST 1.1by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan.

• Have adequate renal, hepatic, bone marrow function as well as adequate coagulationtests [International Normalized Ratio (INR)] and adequate immune function bylymphocyte count.

• Women of child-bearing potential must have a negative serum pregnancy test prior toinitiating study dosing.

• Be willing and able to comply with scheduled visits, the treatment plan, imaging andlaboratory tests.

Exclusion Criteria:

• Active and untreated urinary tract infection, pneumonia, or other systemicinfections.

• Current symptomatic central nervous system (CNS) metastasis.

• Any uncontrolled systemic disease, condition or comorbidity that, in the opinion ofthe Investigator, would interfere with evaluation of study treatment orinterpretation 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 excludedtoxicities.

• Required the use of additional immunosuppression other than corticosteroids for themanagement of an adverse event or have experienced recurrence of an adverse event ifre-challenged, or currently require maintenance doses of >10 mg prednisone orequivalent per day.

• Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir,vaccinia immunoglobulin, imatinib, tecovirimat, or other agents with knownanti-vaccinia activities).

• Underwent major surgery within 4 weeks, or have insufficient recovery fromsurgical-related trauma or wound healing, prior to the planned first dose oftreatment in either Arm.

• Have received prior virus-based gene therapy or therapy with cytolytic virus of anytype.

• Vaccination against smallpox or monkeypox within 1 year of study therapy.

• Any non-oncology vaccine therapy used for prevention of infectious diseases, such asseasonal (influenza) vaccinations, corona virus disease (COVID) vaccination or othervaccines, within 2 weeks of the planned first dose of study drug.

• Clinically significant skin disease as assessed by the Investigator (e.g., severeeczema, 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 excipientspreviously.

• Dementia or altered mental status that would prohibit informed consent, and/orpsychiatric illness/social situations that might interfere or limit compliance withstudy requirements.