SX-682 and Atezolizumab for the Treatment of Advanced or Metastatic, Recurrent Non-small Cell Lung Cancer

Inclusion Criteria

• •Age 18 years and older
• •Ability to understand and willingness to sign a written informed consent document
• •Pathologically or cytologically confirmed non-small cell lung cancer with no known oncogenic EGFR mutation, ALK fusion, ROS1 fusion or RET fusions.
• •* For participants with NSCLC harboring an oncogenic alteration other than the above must have received prior targeted therapy (e.g. small molecule inhibitor therapy or antibody drug conjugates). A wash-out of at least 5 half-lives is required prior to start of study treatment
• •Metastatic or recurrent NSCLC. Stage 3C per 8th edition TNM stage classification is allowed if not amenable to curative surgery or radiation per investigator judgment
• •Participants must have received and progressed on at least 6 weeks of treatment with prior anti-PD-1 or anti-PD-L1 therapy for advanced disease. Also, participants must have received prior platinum doublet chemotherapy. Anti-PD1/PD-L1 therapy may have been received concurrently with chemotherapy or as sequential therapy (e.g. anti-PD1 followed by chemotherapy).
• •* For participants who received neoadjuvant, adjuvant and/or consolidation anti-PD-1 or anti-PD-L1 therapy for stage 1 - 3 NSCLC: If they experienced disease progression ≤ 365 days from initiation of anti-PD-1 or anti-PD-L1 therapy, this counts as the allowed anti-PD-1 or anti-PD-L1 therapy for advanced disease.
• •* For participants who experienced disease progression more than 365 days from initiation of anti-PD-1 or anti-PD-L1 therapy for advanced disease, this is not considered anti-PD-1 or anti-PD-L1 therapy for advanced disease. These patients must have received anti-PD-1 or anti-PD-L1 therapy for stage 4 or recurrent disease
• •Participants must have a minimum of 28 days after the last dose, or 5 half-lives of washout period (whichever is shorter) from last dose of most recent systemic therapy prior to initiation of study treatment, including investigational agents
• •Participants must have at least one site of measurable disease as determined by the investigator, using RECIST v 1.1 criteria documented within 28 days prior to study treatment initiation
• •Participants must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 at the time of informed consent and at the time of treatment initiation
• •Participants must be willing to provide pre-treatment archived specimen (taken within a year of trial entry) or undergo a biopsy procedure if archived specimen is not available.
• •* If biopsy is not deemed safe, it may be waived after discussion with principal investigator (PI)
• •Participants must be willing to provide an on-treatment biopsy, to be obtained at 6 - 9 weeks, if deemed safe by the treating physician
• •Platelet count \> 100,000/μL
• •Absolute neutrophil count \> 1,500/μL
• •Hemoglobin \> 9.0 g/dL. Participants may be transfused to meet this criterion
• •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) \< 2.5 times upper limit of normal
• •Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception: Patients with known Gilbert disease: serum bilirubin ≥ 3 x ULN
• •Creatinine clearance ≥ 30 mL/min
• •For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
• •For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• •Participants of child-bearing potential and sexually active men must agree to use adequate contraception (hormonal methods must be supplemented by barrier method) prior to treatment initiation, during treatment, and for 5 months after the last dose of atezolizumab
• •Known uncontrolled HIV (human immunodeficiency virus) infection
• •* Participants with known HIV infection are allowed if they are receiving anti-retroviral therapy, have CD4+ T-cell count \> 350 cells/µL within 6 months prior to study treatment initiation and no history of AIDS- defining opportunistic infection
• •Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study
• •Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent
• •Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• •History of leptomeningeal disease
• •Treatment with investigational therapy within 28 days prior to initiation of study treatment, or 5 half-lives of washout period (whichever is shorter) from last dose of most recent systemic therapy
• •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
• •Known allergy or hypersensitivity to any component of the atezolizumab formulation