A Phase 1/1b tolerability study of rilotumumab alone or in combination with cisplatin and capecitabine in Japanese patients with gastric cancer

To evaluate the safety (including adverse events and dose-limiting toxicities [DLTs]), tolerability, pharmacokinetics and antitumor activity of the investigational MET inhibitor rilotumumab alone in patients with advanced solid tumors (Part 1) or in combination with cisplatin plus capecitabine (CX) in patients with MET-positive advanced gastric or gastroesophageal junction cancer (Part 2). Adult patients received 10 or 20 mg/kg intravenous (IV) rilotumumab every 2 weeks (Part 1) or 15 mg/kg IV rilotumumab every 3 weeks plus 80 mg/m2 cisplatin on Day 1 and 1000 mg/m2 capecitabine twice daily on Days 1-14 of every 21-day cycle (Part 2). Nine patients enrolled in Part 1; 12 patients enrolled in Part 2. One DLT occurred (Grade 3 decreased appetite and stomatitis [Part 2]). Adverse events related to any treatment occurred in 17 patients (81%) and were Grade ≥3 in nine patients (43%). Rilotumumab pharmacokinetics appeared linear, and exposure was unaffected by CX. No patient who received rilotumumab monotherapy in Part 1 had a response. In Part 2, five of eight patients (63%) with measureable disease at baseline had a partial response and two patients (25%) had stable disease; median (95% CI) progression-free survival was 7.0 (2.4-15.4) months; overall survival was 18.2 (5.6-20.4) months. In combination with CX, rilotumumab appeared tolerable and showed antitumor activity in Japanese patients with MET-positive gastric/gastroesophageal junction cancer. However, owing to the results of recent Phase 3 trials of MET inhibitors (including rilotumumab), further development of rilotumumab in this setting is not being pursued. ClinicalTrials.gov Identifier: NCT01791374.