The purpose of this clinical trial is to evaluate the safety, tolerability, preliminary efficacy, and immunogenicity of EVM14 administered intramuscularly (IM) combination with Ivonescimab in patients with sq-NSCLC.

Inclusion Criteria:

1. Pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous non-small-cell lung cancer (sq-NSCLC), which is unresectable or not curable by definitive concurrent/sequential chemoradiotherapy.
2. Known positive PD-L1 expression in tumor tissue prior to enrollment, with Tumor Proportion Score (TPS) ≥ 1% assessed via the 22C3 assay.
3. No prior systemic anti-tumor therapy. Neoadjuvant/adjuvant systemic chemoradiotherapy for curative intent in non-metastatic disease, or definitive concurrent/sequential chemoradiotherapy for locally advanced disease, are permitted, provided disease progression occurs ≥ 6 months after the last treatment.
4. Patients with at least 1 measurable lesion as defined per RECIST v1.1.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
6. Life expectancy ≥ 6 months.
7. Patients must have adequate organ function.

Exclusion Criteria:

1. Has disease that is suitable for local treatment administered with curative intent.
2. Cannot provide sufficient tumor slides for biomarker testing.
3. Has a diagnosed and/or treated additional malignancy within 5 years prior to the first dose of study treatment except for: curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, and curatively resected in situ breast, cervical cancer, and prostate cancer.
4. Active central nervous system (CNS) metastases. Patients with clinically stable brain metastases are eligible for enrollment.
5. Has active autoimmune disease that has required systemic treatment in past 2 years or history of autoimmune disease that has possibility of relapse or at risk of having these conditions.
6. Has received prior systemic anti-angiogenic therapy or any tumor-directed immunotherapy
7. The left ventricular ejection fraction (LVEF) < 50% during the screening period.
8. Patients known to be human immunodeficiency virus (HIV)-positive.