Author of

• 36555

  +

  P86 - Targeted Therapy - Clinically Focused - New Target (ID 263)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Targeted Therapy - Clinically Focused
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 36564

    +

    P86.08 - Phase 2 Study of Zenocutuzumab (MCLA-128), a Bispecific HER2/HER3 Antibody in NRG1 Fusion-Positive Advanced Solid Tumors (ID 3619)

    00:00 - 00:00  |  Presenting Author(s): Alison M Schram
    • Abstract
    • Slides

    Introduction
    

    Neuregulin 1 (NRG1) gene fusions are oncogenic drivers in multiple cancer types. NRG1 fusion proteins bind to HER3 and signal through HER2/HER3 heterodimers, leading to increased downstream signaling and tumor growth. Clinical responses to agents that target this pathway have been reported. Zenocutuzumab (Zeno, MCLA-128) is a HER2/HER3 bispecific antibody that binds to or ‘docks’ onto the more abundant cell surface HER2 protein, potently blocking NRG1 fusion protein binding and preventing HER2/HER3 dimerization. As an initial proof-of-concept, three patients with chemotherapy-resistant NRG1­-positive KRAS-wild-type pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) who received Zeno through FDA-approved single-patient protocols showed significant tumor shrinkage. These data supported the further evaluation of Zeno in NRG1 fusion-positive cancers. A version of this Clinical Trials in Progress abstract was presented previously at ESMO Congress 2019 (685TiP, Schram et al. Reused with permission) and ASCO Virtual Congress 2020 (#302671; © 2020 American Society of Clinical Oncology, Inc. Reused with permission. All rights reserved).

    Methods
    

    The eNRGy trial is a global, open-label, multicenter phase 2 trial of Zeno in patients with solid tumors harboring NRG1 gene fusions. Main eligibility criteria include previously treated, locally advanced unresectable or metastatic NRG1 fusion-positive cancer. Genomic screening of tumor tissue is performed by local (with post-hoc central confirmation) or central (RNA sequencing) laboratories. Three cohorts of patients with NRG1 fusion-positive cancers are being enrolled: NSCLC, pancreatic cancer, and other solid tumors. The primary endpoint in all cohorts is investigator-assessed objective response rate (RECIST v1.1), and the key secondary endpoint is duration of response. Other secondary endpoints include progression-free and overall survival. Eligible patients receive a dosing regimen of 750 mg of Zeno (2-hour infusion), every 2 weeks, in 4-week cycles. The study is actively accruing patients in more than 30 sites across North America, Europe, and Asia.

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.