A Multicenter Phase II Randomized Trial Of Immunotherapy Versus Chemotherapy Guided By Circulating Tumor DNA-Based Molecular Response On Patients With Metastatic NSCLC
This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA (ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy treatment only and which patients will need both immunotherapy and chemotherapy modalities for their treatment regimen.
• Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC
• Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay.
• Patients will require a baseline Guardant360 CDx test prior to enrollment
• Patients willing to undergo serial ctDNA testing as required by protocol
• Patients will be over the age of 18
• Life expectancy ≥12 weeks
• Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator.
• Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization
• ECOG Performance Score ≤2
⁃ Adequate organ function
⁃ Hemoglobin \> 9 g/dL
⁃ Platelets \> 100,000mm3 or 100 x 109/L
⁃ AST, ALT \< 2.5 x ULN with no liver metastases or \< 5x ULN with the presence of liver metastases
⁃ Total bilirubin \< 1.5 x ULN if no liver metastases or \< 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
⁃ Absolute neutrophil count (ANC) \> 1500 cells/mm3
⁃ Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation
⁃ Willing to use highly effective contraceptive measures if child-bearing potential or if the patient's sexual partner is a woman of childbearing potential: a. Female subjects should be using a highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to starting of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: i. Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not a tubal ligation b. Male subjects should be willing to use barrier contraception