Clinical Research Directory

Criteria: * Patients must have pathologically confirmed non-small cell lung cancer * Early Stage NSCLC Stage IA2 - IIA (tumor size \> 1cm and ≤ 5cm, N0M0), select IIB (tumor size \>5cm and ≤ 7cm, N0M0). Multiple (up to 2) primary lung cancers allowed. Isolated parenchymal recurrences (tumor size ≤ 7cm and up to 2 separate ipsilateral lesions) of initially TanyN0M0 disease. ° Note: The determination of two primary NSCLCs will be based on pathologic and genomic differentiation. * No known sensitizing EGFR or ALK alterations * Disease amenable to 3, 5 or 8 fraction SBRT as judged by treating radiation oncologist. Tumors that have extensive overlap with the mediastinum for which a more protracted radiotherapy course (i.e. 15 fraction) would be needed are excluded. * No primary tumor (Gross Target Volume, GTV) that contacts the esophagus * Unwilling to undergo surgical resection or ineligible for surgical resection as determined by review of a multidisciplinary team for surgical candidacy * Patients with isolated parenchymal recurrences should have completed all prior definitive therapy (surgery, radiotherapy, chemotherapy) for at least 6 months * No prior receipt of immune checkpoint inhibitors * No prior thoracic radiation that precludes definitive SBRT of current disease * Age ≥ 18 * ECOG Performance Status of ≤ 1 * Not Pregnant and Not Nursing * Female patients of childbearing age must have negative serum pregnancy test results * Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of the ivonescimab. * Unsterilized male patient having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until 90 days after the last dose of ivonescimab * Adequate hematologic function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3 * Platelets ≥ 100,000 cells/mm\^3 * Hemoglobin ≥ 9 g/dl * Adequate coagulation parameters * prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN * partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy) This applies only to patients who are not on therapeutic anti-coagulation.Patients receiving therapeutic anti-coagulation should be on a stable dose. * Adequate renal function defined as follows: * Urine protein \< 2+ or 24hour urine protein quantification \< 1.0g * Creatinine clearance (CrCL) of ≥30 mL/min by the Cockcroft-Gault formula CrCl (mL/min) = \[140 - age (years)\] x weight (kg) {x 0.85 for female patients} 72 creatinine (mg / dL) * Adequate hepatic function defined as follows: * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled) * AST and ALT ≤2.5 x institutional ULN * Adequate cardiac function defined as follows: * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. * To be eligible for this trial, patients should be class 2B or better * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * No active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). * The following are exceptions to this criterion: * Vitiligo or alopecia * Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients not on biologic therapy without active disease in the last 2 years may be included, but only after consultation with the study physician * Patients with celiac disease controlled by diet alone * No history of allogenic organ transplantation with exception of corneal transplantation * No history of idiopathic pulmonary fibrosis or evidence of interstitial lung disease on imaging * No known severe concurrent illness: * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Active or recurrent hepatic disorders including cirrhosis, hepatitis B and C. Patients with a past or resolved HBV infection, defined as the presence of hepatitis B core antibody (anti-HBc) and absence of hepatitis B surface antigen (HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. * Active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice) * Human Immunodeficiency Virus (positive HIV 1/2 antibodies). * Active chronic infections requiring systemic therapy. * History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months of enrollment * History of any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event , as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 6.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollment * History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment * Acute exacerbation if COPD requiring hospitalization in the last 4 weeks * Pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 6 * No Major surgical procedures or serious trauma within 4 weeks prior to enrolment, or plans for major surgical procedures within 4 weeks after the first dose. * No poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy * No history of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to: * Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) ° Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed. * Nasal bleeding /epistaxis (bloody nasal discharge is allowed) * Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to randomization is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution * Concomitant Medications * No treatment with a monoclonal antibody within 4 weeks prior to study treatment Day 1 (intraocular bevacizumab is acceptable). * No biologic drugs targeting the immune system (e.g., TNF blockers, anakinra, abatacept, tocilizumab) within 4 weeks prior to study treatment Day 1 * No prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways * No current or prior use of a systemic immunosuppressive medication within 4 weeks prior to study treatment Day 1. The following are exceptions to this criterion: i. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,intra articular injection) ii. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent for less than 30 days. iii. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) iv. Systemic glucocorticoid replacement for conditions such as adrenal or pituitary insufficiency. * Allergies * No history of allergic reaction to the study agent(s), compounds of similar chemical or biologic composition to the study agent (s) (or any of its excipients).