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Nora Pencheva

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    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      OA02.05 - First-In-Human Phase 1/2 Trial of Anti-AXL Antibody–Drug Conjugate (ADC) Enapotamab Vedotin (EnaV) in Advanced NSCLC (Now Available) (ID 343)

      10:30 - 12:00  |  Author(s): Nora Pencheva

      • Abstract
      • Presentation
      • Slides


      AXL, a transmembrane receptor tyrosine kinase, is aberrantly expressed in various cancers, and associated with poor prognosis and treatment resistance. AXL overexpression is associated with resistance to PD-1 immune checkpoint inhibitors (Hugo et al. 2016). EnaV, a novel ADC of anti-AXL human IgG1 and monomethyl auristatin E, demonstrated potent anti-tumor activity in preclinical models, including NSCLC (Boshuizen et al. 2018). In a phase 1, dose escalation, multi-cohort trial (NCT02988817) in heavily pretreated patients with relapsed or refractory solid tumors, EnaV 2.2 mg/kg once every 3 weeks (1Q3W; recommended phase 2 dose) showed preliminary anti-tumor activity. Here we present initial results from patients with NSCLC in the phase 2a, expansion phase of this trial.


      We analyzed data from EnaV 2.2 mg/kg 1Q3W, in the cohort of pretreated patients with stage III/IV NSCLC without sensitizing EGFR mutations (EGFR WT) or ALK rearrangements (ALK-) who had failed ≤4 prior lines of therapy, including platinum-based chemotherapy and PD-1/PD-L1 inhibitor (either in combination or sequentially). Endpoints include safety, objective response rate (ORR; RECIST 1.1), and AXL expression in fresh tumor biopsies (immunohistochemistry).


      In the EGFR WT/ALK- cohort, 26 patients (median age 65.5 years, range 38–74; 57.7% male) with ECOG PS of 0 (11.5%) or 1 (88.5%) have been enrolled. Most patients (23/26) were treated with a checkpoint inhibitor. At a median follow-up of 18 weeks (range: 2–54), the most common (≥20%; any grade) treatment-emergent adverse events (TEAEs) were fatigue, constipation, nausea, decreased appetite, decreased weight, diarrhea, and vomiting. Two patients had a TEAE leading to dose reduction. Grade ≥3 TEAEs occurred in 12 patients, with the most common being gastrointestinal disorders in eight patients (constipation [n=1]; colitis, diarrhea, nausea, vomiting [n=2 each]; abdominal distension [n=1]. The confirmed ORR is 19% (95% CI: 8.5%, 37.9%). The disease control rate (CR+PR+SD) is 50% (13/26). Nine of 12 (75%) evaluable fresh biopsies were positive for AXL tumor cell staining.


      In this high unmet need patient population, with advanced EGFR WT and ALK- NSCLC who are pretreated with PD-1/PD-L1 inhibitors and platimum-based therapies, EnaV monotherapy demonstrated a manageable safety profile and encouraging preliminary clinical activity. This cohort has expanded to allow up to 60 patients to gain further knowledge of AXL as a potential biomarker for responsiveness to EnaV and to gather additional data on safety and efficacy. Funding: Genmab A/S

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