1490PDA phase Ia/IIa trial of Sym015, a MET antibody mixture, in patients with advanced solid tumours

Abstract Background MET gene amplification/mutation is implicated in oncogenesis of many tumor types. Sym015 is a recombinant antibody (Ab) mixture containing 2 humanized Abs binding non-overlapping epitopes on MET which has superior preclinical activity compared to other MET Abs. Here we present interim results from the First in Human study of Sym015. Methods In part 1 dose escalation, Sym015 was evaluated on every 2-week (q2w) schedule at 6/12/18/24 mg/kg doses in late line advanced solid tumor patients (pts). Based on PK/PD assessment, 18 mg/kg loading dose followed by 12 mg/kg q2w was selected as RP2D. The on-going Part 2 Dose expansion enrolls pts with MET amplification (METAmp >5 MET copies by Next Generation Sequencing (NGS) or FISH MET/CEP7 ratio >2.2 updated to ≥ 3.0) and/or MET exon 14 deletion (METEx14Δ) positive tumors. Central FISH confirmation of tumor MET status and longitudinal circulating tumor (ct)DNA profiling is performed. Results By April 2019, 51 pts (median age 61 yrs) have been treated, 12 pts in Part 1 and 39 pts in Part 2, the majority are non small cell lung cancer (NSCLC; 14 pts; 6 METAmp,7 METEx14Δ, 1 both) and gastric cancer (GC; 12 METAmp pts). Treatment-related adverse events (TRAE) occurred overall in 41,2%; TRAE ≥ gr3 in 9,8% (edema, colitis, septic shock, hypoalbuminemia, hypophosphatemia, increased amylase). No pts discontinued or died due to TRAE. The most common TRAE of ≥ 5% were fatigue 15.7%, peripheral edema 7,8%, nausea, decreased appetite, pruritus and abdominal pain reported by 5.9% of pts each. The table shows preliminary efficacy in NSCLC patients. Sym015 PK was slightly non-linear, with a dose-dependent t½ of 7-10 days for the first dose. 83% METAmp concordance (10/12 samples) between tumor and blood was observed. Table:1490PDNSCLC PtMET Status (Local Assessment)Best Response (Best % Change From Baseline)Previous MET TKI therapyDuration of Response (weeks)1METAmp NGS 6.8 CopiesPR (-53%)No802METAmp NGS >5 CopiesSD (-29%)No9, Ongoing3METAmp NGS >5 CopiesSD (+3%)No9, Ongoing4METEx14ΔSD (-28%)No7, Ongoing5METAmp FISH MET/ CEP7:4.9SD (+6%)No116METEx14ΔSD (-4%)Yes87METEx14ΔSD (-21%)Yes158METEx14ΔSD (-20%)Yes89METAmp SISH MET/ CEP7: 15.2PendingNoOngoing10METEx14ΔPendingYesOngoing11METEx14Δ + METAmpPendingPendingOngoing12METEx14ΔPendingNoOngoing13METEx14ΔPendingNoOngoing14METEx14ΔNot EvaluableYesNot Evaluable Conclusions Sym015 was well tolerated with early evidence of antitumor activity. Predictive biomarker analysis