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.
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