Randomized

All enrolled patients who are randomized to the ONC-392 arm will receive ONC-392 for up to 17 cycles in approximately 1 year or until discontinuation criteria are met. Patients who are randomized to the docetaxel arm will receive docetaxel 75 mg/m2 Q3W for up to 17 cycles in approximately 1 year or until disease progression per RECIST 1.1.

• Histologically- or cytologically- confirmed diagnosis of metastatic squamous NSCLC, metastasis can be regional lymph nodes or distant organs.
• Radiographic disease progression after treatment with the most recent line of treatment being 3a or 3b as follows: a. At least 12 weeks of standard doses of PD-1/PD-L1 inhibitor in combination with platinum-containing doublet chemotherapy; b. Prior treatment with at least 2 cycles of a platinum-containing doublet chemotherapy, followed by at least 12 weeks of standard doses of PD-1 or PD-L1 inhibitor-based immunotherapy. Antibodies against CTLA-4, LAG-3, TIGIT, VEGF or VEGFR in combination with PD-1/PD-L1 inhibitor are allowed

• Patients who have documented non-squamous histology type or with targetable mutations or genomic alterations in the following genes: EGFR, ROS1, MET, BRAF, RET, NTRK, ALK or HER2. Patients with mutation or genomic alterations in KRAS are not excluded
• Patients who have active or symptomatic brain metastases or evidence of progression within 4 weeks prior to study drug dosing. Palliative radiation or radiosurgery for brain metastases within 14 days from first day of study treatment or patients cannot achieve neurologically stable without > 10 mg daily prednisone or equivalent treatment. Patients with treated, stable brain metastases or with untreated asymptomatic brain metastases (