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Anthony Brown



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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • 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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      P2.04-27 - Ph II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Advanced NSCLC (ID 14307)

      16:45 - 18:00  |  Author(s): Anthony Brown

      • Abstract

      Background

      Bemcentinib (BGB324) is a first-in-class, highly selective oral inhibitor of the AXL tyrosine kinase currently in phase II clinical development across several cancer types. AXL overexpression has been observed in pts failing anti-PD-1 therapy in several cancers whereas AXL inhibition via bemcentinib has shown synergistic effect with checkpoint blockade in pre-clinical models of NSCLC.

      In pts with advanced, pre-treated NSCLC, bemcentinib monotherapy led to disease stabilisation in 2 out of 8 pts including evidence of tumour reduction. Combination therapy of bemcentinib with EGFR inhibition indicated the potential of AXL blockade to reverse resistance to targeted therapy in advanced EGFR therapy resistant NSCLC. Evidence of immune activation following bemcentinib monotherapy was observed in AML patients.

      This open label, single-arm, two-stage Phase 2 study was designed to test whether AXL inhibition may increase the efficacy of pembrolizumab in patients with advanced, previously treated adenocarcinoma of the lung.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with documented Stage IV adenocarcinoma of the lung who had progressed on previous platinum chemotherapy and – if applicable – at least one line of licensed EGFR or ALK targeted therapy, received 200 mg/d bemcentinib po and 200 mg/q3wk pembrolizumab iv. Patients were required to consent to a fresh pre-treatment biopsy. Tumour assessments were done 9-weekly. The primary endpoint was ORR. Tumour biopsies were analysed for PD-L1 and AXL as well as immune cell populations. Plasma protein biomarker levels were measured using the DiscoveryMap v3.3 panel (Myriad RBM) in patients pre-dose and at C2D1.

      4c3880bb027f159e801041b1021e88e8 Result

      As of time of writing, the study had fully recruited its first stage. Of 24 patients enrolled, 14 were ongoing. 6 of 10 patients who had reached their first scan showed evidence of tumour shrinkage including 3 pts with partial responses in their target lesions. 2 patients had stable disease. There were no grade 4 treatment-related events. Dose reduction from 200 to 100 mg/d of bemcentinib as a consequence of adverse events was required in 12% of patients. Correlation of AXL and PD-L1 expression with response was evaluated. Soluble AXL plasma levels were increased following one cycle of treatment indicative of target engagement.

      8eea62084ca7e541d918e823422bd82e Conclusion

      A preliminary analysis of response to combination treatment during the first stage of this study as well as biomarker correlation will be presented at the meeting. Clinical trial information: NCT03184571

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