A Phase 2 Trial of SX-682 and Atezolizumab in Patients With Advanced NSCLC Who Progressed on Prior Chemotherapy and Immune Checkpoint Inhibitor (ICI) Therapy
This phase II trial tests how well SX-682 and atezolizumab works for the treatment of non-small cell lung cancer (NSCLC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic), and has come back after a period of improvement (recurrent). SX-682 blocks proteins that may be able to stimulate the immune system to kill and eliminate tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving SX-682 and atezolizumab may be effective for the treatment of advanced or metastatic, recurrent NSCLC.
• 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
• Negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to initiation of study treatment for participants of childbearing potential. Pregnant or breast-feeding women or intention of becoming pregnant during study treatment or within 5 months of last dose of atezolizumab are not eligible