A PHASE 1 STUDY TO EVALUATE THE EFFECT OF HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS AND SAFETY OF LORLATINIB IN ADVANCED CANCER PATIENTS
18 Years and older, Male and Female
lorlatinib HEPATIC IMPAIRMENT
This is a phase 1 study in advanced cancer patients with varied hepatic fucntions to evaluate the potential effect of hepatic impairment on pharmacokinetics and safety of lorlatinib and provide dose recommendation for patients with hepatic impairment if possible.
This will be a Phase 1, open label, multi center, multiple dose, non randomized, Phase 1
clinical trial of lorlatinib in advanced cancer patients with varying degrees of hepatic
impairment and necessary age , weight , and gender matched prospect normal hepatic function
patients. This study is intended to evaluate the potential effect of hepatic impairments on
the PK and safety of lorlatinib after daily administration of lorlatinib and to provide
dosing recommendation for patients with varied degree of hepatic impairment if possible.
Patients in the study will be assigned to different groups (A1, normal liver function,
control for group B; A2, normal liver function, control for group C; B, mild hepatic
impairment; C, moderate hepatic impairment; D, severe hepatic impairment) according to their
liver function. The enrollment of approximately 76 advanced cancer patients is anticipated in
this study in order to have 8 PK-evaluable patients in each of Groups A1, A2, B and C, and 6
PK-evaluable patients in Group D for final statistical analysis. Evaluable patients are those
who complete the planned PK sample collection on Cycle 2 Day 1 and have no lorlatinib dose
modification until completion of Cycle 2 Day 1 PK evaluation. Patients who are not evaluable
for PK will be replaced. Each patient will be treated with repeated oral once daily doses of
lorlatinib in 21-day cycles until disease progression, patient refusal, or unacceptable
toxicity occurs. The dose schedule may be modified as necessary for individual patients
according to tolerability.