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Phase 1/2 study of single agent MCLA-128, a full length IgG1 bispecific antibody targeting the HER3 pathway: overall safety at the recommended phase 2 dose (R2PD) and preliminary activity in HER2+ metastatic gastric/gastroesophageal junction cancer (GC/GEJ)

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Maria Alsina

Citation

Annals of Oncology (2018) 29 (suppl_8): viii205-viii270. 10.1093/annonc/mdy282

Authors

M. Alsina1, A. Varga2, A. Amatu3, J.H.M. Schellens4, P.O. Witteveen5, V. Boni6, V. Moreno7, K. Bol8, A. Lourbakos8, M. Magin Ferrer9, E. Wasserman10

Author affiliations

  • 1 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 2 Ditep, Gustave Roussy, 94805 - Villejuif/FR
  • 3 Medico Oncologo, ASST Grande Ospedale Metropolitano Niguarda, 20162 - Milan/IT
  • 4 Clinical Pharmacology & Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 5 Hoofd Medische Oncologie, UMC - University Medical Center Utrecht, 3584 CX - Utrecht/NL
  • 6 Medical Oncology, START Madrid-CIOCC HM Hospital Sanchinarro, Madrid/ES
  • 7 Medical Oncology-start Madrid-fjd, University Hospital "Fundacion Jimenez Diaz", 28040 - Madrid/ES
  • 8 Clinical Pharmacology, Merus NV, Utrecht/NL
  • 9 Clinical research, Merus NV, Utrecht/NL
  • 10 Medical Oncology, Merus NV, Utrecht/NL
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Resources

Background

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).

Methods

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.

Results

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+.

Conclusions

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

EudraCT: 2014-003277-42.

Legal entity responsible for the study

Merus NV.

Funding

Merus NV.

Editorial Acknowledgement

Dr Sarah MacKenzie, Oncology Therapeutic Development.

Disclosure

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.

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