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Julio Peguero

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    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.13-10 - Ph I/II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Erlotinib in pts with EGFRm NSCLC   (ID 14272)

      16:45 - 18:00  |  Author(s): Julio Peguero

      • Abstract


      Bemcentinib is a first-in-class, oral, selective AXL TKI which is being evaluated as a combination therapy across several phII clinical trials. Increased AXL expression is associated with innate immune suppression and the appearance of resistance to targeted therapies in models of NSCLC and pt samples. AXL inhibition via bemcentinib prevents the appearance of such resistance in vivo and has shown immunomodulatory effect in AML patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This study was designed to confirm the safety and tolerability of bemcentinib as a monotherapy and when administered in combination with erlotinib (arm A). Pts with activating EGFR mutation driven NSCLC who had progressed on an approved EGFR inhibitor (arm B) or were receiving erlotinib in the first line setting (arm C) were treated with bemcentinib at RP2D in combination with full dose erlotinib to evaluate the potential of bemcentinib to reverse or prevent resistance to EGFR targeted therapy, respectively. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) at C1D1 and C2D1.

      4c3880bb027f159e801041b1021e88e8 Result

      2 out of 8 pts (25%) with stage IV disease who received bemcentinib monotherapy achieved SD for close to 1 year including evidence of tumour shrinkage of 19% in 1 pt. 1 pt who had progressed on previous erlotinib monotherapy (12.5%) achieved a PR receiving bemcentinib in combination with erlotinib and remains on treatment well beyond 2 years later (arm A). A further 3 pts had SD at 6 wks. 11 patients (4 female, median age 58; 38-67) were enrolled in arm B and had received a median of 2 (1 - 4) previous lines of cytotoxic chemotherapy and a median of 2 previous EGFR inhibitors. 2 of these 11 pts (18%) including 1 pt who was refractory to erlotinib therapy at the onset of combination therapy remain on treatment more than 6 months into therapy at the time of writing with best responses of PR and SD, respectively. 1 further pt had SD at 6 weeks. The most common treatment-related AEs have been gastrointestinal and rash.There was no evidence of any impact of bemcentinib on erlotinib pharmacokinetics. Protein biomarkers predictive of pt benefit following bemcentinib treatment were identified.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Bemcentinib can be safely administered in combination with erlotinib to pts with NSCLC and achieves additional benefit in a proportion of patients who do not have T790M and have progressed on EGFR inhibition or are maintained on erlotinib alone. Clinical trial information: NCT02424617.