Phase 1 Experience of Tivantinib in Patients With Hepatocellular Carcinoma (HCC) or Biliary Tract Cancer (BTC)

Results: 53 patients (median age, 63 y) with HCC (n = 42; 79%), cholangiocarcinoma (n = 10; 19%), or gallbladder adenocarcinoma (n = 1; 2%) were included. Of these, 23 patients (43%) received tivantinib monotherapy, and 30 patients (57%) received tivantinib in combination with sorafenib (n = 20; 38%), gemcitabine (n = 8; 15%), or erlotinib (n = 2; 4%). Starting tivantinib BID doses were < 240 mg in 3 (6%), 240 mg in 11 (21%), and 360 mg in 39 (74%) patients. Common treatment-emergent AEs (≥ 15% of patients) were fatigue and anemia (45% each); diarrhea (40%); neutropenia and anorexia (38% each); asthenia (30%); thrombocytopenia, peripheral edema, pyrexia, and nausea (25% each); hyperbilirubinemia (23%); vomiting and alopecia (21% each); rash (19%); leukopenia (17%); and palmar-plantar erythrodysesthesia syndrome, dyspnea, and ascites (15% each). Tivantinib PK analysis indicated peak plasma levels 2 h after oral administration (range, 1-6 h). Tivantinib exposure