A Phase 1/2 Study of TPX-0131, A Novel Oral ALK Tyrosine Kinase Inhibitor in Subjects with ALK+ Advanced or Metastatic NSCLC

A phase 1, first-in-human, open-label study to evaluate the safety, tolerability, PK, and
efficacy of the novel ALK inhibitor TPX-0131 in pretreated subjects with ALK+ advanced or
metastatic non-small cell lung cancer (NSCLC).

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.