Phase 1/2 study to evaluate the safety and anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab.

• Monotherapy ANV600 = PD-1 targeted IL-2 variant, targets CD8 T-cells
• Combination of ANV600 and pembrolizumab

Determine maximum tolerable dose and recommended phase 2 dose either as monotherapy or in combination with pembrolizumab.

• Histologically or cytologically confirmed unresectable or metastatic squamous or nonsquamous non-small cell lung cancer (NSCLC) as per American Joint Committee on Cancer (AJCC) ed. 8 not eligible for an approved targeted therapy
• Have received a platinum-based chemotherapy either in combination with immunotherapy or in second line after first line anti-PD(L)1 in monotherapy
• Progressed on or after treatment with a PD-1/L1 checkpoint inhibitor either as monotherapy, or in combination with platinum-based chemotherapy

• Have known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
• History of an acute coronary event (e.g., myocardial infarction) within 3 months prior to study Day 1, uncontrolled and symptomatic coronary artery disease, or congestive heart failure NYHA Class III/IV