Adverse Events Notes

TEAEs and grade ≥3 TEAEs were reported by 23 (100%) and 16 (70%) patients, respectively (Table 3). No patients died because of a TEAE. A total of six patients (26%) experienced hypothyroidism; all events were grade 1 or 2 (3 patients each). These patients were treated with levothyroxine, and none discontinued study treatment or had a dose reduction due to hypothyroidism. A review of available thyroid stimulating hormone and thyroxine laboratory data from patients did not indicate any pattern associated with study drug treatment. Treatment‐related TEAEs (per investigator assessment) and grade ≥3 treatment‐related TEAEs were reported by 21 (91%) and 10 (43%) patients, respectively (Table 1). The most commonly reported treatment‐related TEAEs were fatigue; headache; increased blood alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase; and decreased appetite. Fatigue was the most commonly reported grade ≥3 treatment‐related TEAE (4 patients [17%]). The only serious adverse event considered related to the study treatment was grade 3 cholestatic hepatitis in cycle 3. The event occurred 7 days after the last dose of ramucirumab and on the same day as the last scheduled dose of merestinib, which was omitted. This patient discontinued study treatment after the event worsened to grade 4. No other patients discontinued study treatment due to a TEAE. A total of 20 patients (87%) experienced AESIs for ramucirumab, of whom 10 (43%) had grade ≥3 AESIs (Table 4). AESIs experienced by ≥3 patients included liver injury or failure events (liver function abnormalities and other hepatic events), bleeding or hemorrhagic events, proteinuria, hypertension, and thromboembolic events. Fourteen patients (61%) experienced liver function abnormalities, of whom five experienced grade 3 or 4 events. Of these patients, 11 had liver metastases at baseline, and 2 developed liver metastases at progression. The majority of liver events were reversible laboratory abnormalities of mild or moderate severity. Five patients (22%) experienced a bleeding or hemorrhagic event. There were no events of gastrointestinal perforation, reversible posterior leukoencephalopathy syndrome, fistula formation, or surgery and impaired wound healing.