Assessment of the Safety and Efficacy of Balstilimab in Combination With Botensilimab for the Treatment of Non-Small Cell Lung Cancer (IMMONC0008)

Inclusion Criteria

• •1. Histologically and IHC confirmed diagnosis of metastatic NSCLC which has not received any prior anticancer medicinal therapy for metastatic disease.
• •2. Negative for actionable EGFR mutations and ALK rearrangements.
• •4. Documented informed consent of the participant and/or legally authorized representative
• •5. ≥ 18 years of age.
• •6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• •7. Life expectancy ≥ 3 months.
• •8. Patients should have measurable metastatic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST guidelines.
• •9. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 7 days prior to day 1 of protocol therapy) (except subjects with Gilbert syndrome who must have a total bilirubin level of ≤3.0 × ULN).
• •10. Aspartate aminotransferase (AST) ≤ 2.5 x ULN, unless presence of liver metastases for which ≤ 5 x ULN is allowed (within 7 days prior to day 1 of protocol therapy).
• •11. Alanine aminotransferase (ALT) ≤ 2.5 x ULN, unless presence of liver metastases for which ≤ 5 x ULN is allowed (within 7 days prior to day 1 of protocol therapy).
• •12. Creatinine clearance ≥ 45 ml/min (within 7 days prior to day 1 of protocol therapy).
• •13. Alkaline phosphatase ≤ 3 x ULN (within 7 days prior to day 1 of protocol therapy).
• •14. Hemoglobin ≥ 9 g/dl (within 7 days prior to day 1 of protocol therapy).
• •15. Absolute neutrophil count (ANC) ≥ 1500/ul (within 7 days prior to day 1 of protocol therapy).
• •16. Platelets ≥ 100,000/mm\^3 (within 7 days prior to day 1 of protocol therapy).
• •17. Albumin ≥ 3.0 g/dl (within 7 days prior to day 1 of protocol therapy).
• •18. Women of childbearing potential (WOCBP): negative serum pregnancy test (within 7 days prior to day 1 of protocol therapy)
• •a) Females of non-childbearing potential are defined as: i. ≥ 50 years of age and has not had menses for greater than 1 year ii. Amenorrheic for ≥ 2 years without a hysterectomy and bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation iii. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation.
• •19. Male and female patients of reproductive potential must use effective methods of contraception (defined in Appendix A) or abstain from sexual activity for the course of the study through at least 90 days after the last dose of balstilimab and/or botensilimab
• •20. Is willing and able to comply with the requirements of the protocol.
• •11. Any evidence of current interstitial lung disease (ILD) or pneumonitis, or prior history of ILD or non-infectious pneumonitis requiring glucocorticoids.
• •12. Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• •13. History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• •14. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster \< 7 days before C1D1. For vaccines requiring more than 1 dose, the full series should be completed prior to C1D1, when feasible. Booster shot not required but also must be administered \> 7 days from C1D1 or \> 7 days from future cycle on study.
• •15. Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required.
• •16. Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Subjects who are receiving or who have received anti-HBV therapy and have undetectable HBV DNA for at least 180 days prior to enrollment are eligible. Serological testing for HBV at screening is not required.
• •17. Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Subjects on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 180 days prior to enrollment. Serological testing for HCV at screening is not required.
• •18. Known active tuberculosis. Tuberculosis testing at screening is required.
• •19. Grade 3 or above neuropathy at the time of enrollment.
• •20. Dependence on total parenteral nutrition or intravenous hydration.
• •21. Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
• •22. Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).