A phase I study of LY3164530, a bispecific antibody targeting MET and EGFR, in patients with advanced or metastatic cancer

• DOI: 10.1007/s00280-018-3623-7
• Publication Date: 2018-06-20T02:35:44Z
• Authors: Amita Patnaik; Michael Gordon; Frank Tsai; Kyri Papadopoulous; Drew Rasco; S. Muralidhar Beeram; Siqing Fu; Filip Janku; Scott M. Hynes; Sushma R. Gundala; Melinda D. Willard; Wei Zhang; Aimee Bence Lin; David Hong
• Keywords: Bispecific antibody

The phase I study characterized the safety, pharmacokinetics, anti-tumor activity, and recommended II dose/schedule of LY3164530 in patients with advanced or metastatic cancer.Patients received on days 1 15 (Schedule 1: 300, 600, 1000, 1250 mg) Days 1, 8, 15, 22 2: 500 600 each 28 cycle. Dose escalation used a modified toxicity probability interval model.Dose defined maximum tolerated dose (MTD) 1000 mg Schedule 2. Treatment-emergent adverse events related to treatment were consistent epidermal growth factor receptor (EGFR) inhibition included maculopapular rash/dermatitis acneiform (83%, Grade 3/4 17%), hypomagnesemia (55%, 7%), paronychia (35%), fatigue (28%, 3%), skin fissures (24%), hypokalemia (21%, 7%). Partial response was achieved three 2 colorectal cancer (n = 2) squamous cell cancer. Overall rate (ORR) 10.3%, disease control (ORR + stable [SD]) 51.7 17.2% had SD ≥ 4 months. vivo stability bispecific antibody confirmed. provided greater more mesenchymal-epithelial transition (MET)/EGFR throughout dosing than 1.Although this MTD pharmacokinetics both schedules, significant toxicities associated EGFR lack potential predictive biomarker limit future development. Nonetheless, results provide insight into development therapy.