Inclusion Criteria:  Age ≥ 18 (or as required by local regulation). Histological or cytological confirmation of advanced/metastatic ALK+ NSCLC. Pretreated with up to three prior lines of an ALK TKI treatment, including at least one prior line of a second or third-generation ALK TKI (alectinib, brigatinib, ensartinib, or lorlatinib) in Phase 1. ECOG performance status ≤ 1. Existence of measurable or evaluable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria). Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible. Adequate organ function.  Exclusion Criteria:  Major surgery within four weeks of the start of TPX-0131 treatment. Clinically significant cardiovascular disease  Any of the following cardiac criteria:  Mean resting corrected QT interval (QTc) > 470 msec obtained from three ECGs and any factors that increase the risk of QTc prolongation or arrhythmic events Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity). Gastrointestinal disease or other malabsorption syndromes that would impact drug absorption. Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers. Subjects with current or anticipated need for drugs that are sensitive CYP2C9 substrates with narrow therapeutic indices.