A phase 1, open label, dose escalation study to investigate the safety, tolerability, and pharmacokinetics of MG1102 (apolipoprotein(a) Kringle V) in patients with solid tumors.

Purpose MG1102 is a potent inhibitor of angiogenesis in both in vitro and in vivo models. The purpose of the study was to investigate the safety and tolerability, pharmacokinetic (PK) profile, and preliminary antitumor efficacy of MG1102. Methods Patients with refractory solid tumors were eligible. Each patient received 1 dose of MG1102 followed by a 6-day rest period, during which they underwent PK assessments and safety monitoring. If the initial dose was tolerated, the patient continued with the 21-day treatment of MG1102 (5 days on, 2 days off for 3 weeks). Dose escalation was planned in 6 cohorts (6, 12, 24, 48, 96, and 192 mg/m2 ). Primary objectives included safety and maximum tolerated dose (MTD) assessment. Secondary objectives included assessment of PK, pharmacodynamics, and efficacy. Results A total of 16 patients were enrolled and 12 (75%) completed the study. The most common cancer type was colorectal cancer (n = 10). There was no dose limiting toxicity and the MTD was not reached at 192 mg/m2 . The most frequent treatment-emergent adverse events were gastrointestinal disorders, including nausea (30.8%), abdominal pain (23.1%), constipation (23.1%), and dyspepsia (23.1%). The PK of MG1102 was slightly less than dose proportional from Cohorts 3 to 6. Among 13 response-evaluable patients, 1 unconfirmed partial response (PR) was seen (in the 48 mg/m2 cohort) and 4 patients had stable disease. Conclusions The safety profile of MG1102 was generally manageable and the toxicities resolved quickly. Potential antitumor activity was observed with 1 unconfirmed PR (60% size reduction).