MCLA-128 is a novel bispecific antibody targeting HER2 and HER3 receptors with enhanced antibody-dependent cell-mediated cytotoxicity. No DLT was seen during dose escalation and the R2PD was 750 mg q3w. We report safety across solid tumor expansion indications, and efficacy in metastatic GC/GEJ patients (pts).
Safety, PK, immunogenicity and biomarkers were evaluated in heavily pretreated advanced metastatic cancer pts treated with MCLA-128, 750 mg q3w, 2-hr IV. Response (RECIST 1.1) and clinical benefit rate (CBR; CR + PR + SD ≥ 12 wks) were assessed in HER2-positive GC/GEJ pts who had progressed on trastuzumab.
As of 15 Feb 2018, 100 pts were enrolled in the expansion cohorts, 97 of whom were treated. Mean age was 58 ± 11 years, M/F: 26/74, ECOG PS 0/1: 36/63 (1 missing). Pts received a median of 2 MCLA-128 cycles (range 1 - 27). Common related AEs were infusion-related reactions (19%), diarrhea (17%), asthenia/fatigue (15%), nausea (6%), and decreased appetite (5%). Four (4%) pts had suspected related grade 3-4 AEs. No clinically significant LVEF decline (>10% from baseline and LVEF <50%) was seen. Mean T1/2 was ∼100 hr (n = 89). Steady state serum concentrations of MCLA-128 were achieved after 2 cycles. As of 25 Mar 2018, 25 GC/GEJ pts were evaluable for response, with a median 3 metastatic sites (range 1-6), and progression on 1-2 prior anti-HER2 agents. They received a median of 2 MCLA-128 cycles (range 1-17). 1 pt had a confirmed CR (8+ cy), 9 pts had SD (sustained: 4, 5, 6, 12, 17 cy). CBR was 24% (6/25 pts). Based on central analysis variable HER2 levels were observed by HER2 IHC, and HER2 amplification was confirmed by FISH in all CBR patients. 4 of the 6 CBR pts had HER2 IHC 3+.
MCLA-128 is very well tolerated with mainly grade 1/2 AEs. Promising single agent antitumor activity was seen in heavily pretreated GC/GEJ pts progressing on anti-HER2 therapy. Further clinical exploration of MCLA-128 in GC/GEJ pts is warranted.
Clinical trial identification
Legal entity responsible for the study
Dr Sarah MacKenzie, Oncology Therapeutic Development.
M. Alsina, A. Varga, A. Amatu, J.H.M. Schellens, P.O. Witteveen, V. Boni, V. Moreno: Institution participates in corporate-sponsored research (Merus NV). K. Bol, A. Lourbakos, M. Magin Ferrer, E. Wasserman: Employee: Merus NV.