|The following article features coverage from the Society of Immunotherapy of Cancer (SITC) 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Combination treatment with pembrolizumab plus the AXL inhibitor bemcentinib was well tolerated and demonstrated antitumor activity among patients with AXL-positive non-small cell lung cancer (NSCLC) that was previously treated with an immune checkpoint inhibitor (ICI), according to the results of a phase 2 trial presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).
AXL is a transmembrane receptor tyrosine kinase that promotes resistance to T-cell–mediated elimination and is associated with poor outcomes and anti–programmed cell death 1 (PD-1) treatment failure. Bemcentinib is a first-in-class, selective AXL kinase inhibitor that showed immune-mediated antitumor effects in preclinical studies.
“Presumably, bemcentinib inhibition of AXL reverses this state of immune suppression in the microenvironment, and promotes checkpoint inhibitor re-engagement,” James Spicer, PhD, FRCP, of King’s College London, and presenter of the study, said.
The single-arm, 2-stage phase 2 BGBC008 trial treated patients with previously treated metastatic NSCLC with bemcentinib plus pembrolizumab. Patients were assigned to 1 of 3 cohorts: cohort A included 48 patients who previously received chemotherapy; cohort B included 29 patients who previously received an ICI, and cohort C included 29 patients who had previously received combination pembrolizumab plus chemotherapy.
The primary endpoint was objective response rate (ORR) and the secondary endpoints included progression-free survival (PFS), OS, disease control rate (DCR), and safety. Biomarker analysis was an exploratory analysis.
Results from cohort A were previously reported, including a median overall survival (OS) of 17.3 months compared with 12.4 months for AXL-positive or -negative disease, respectively. The present interim analysis was of the 16 patients evaluable for efficacy from cohort B.
At baseline, cohort B comprised 3 patients who were previously treated with 1 therapy and 9 who had received at least 2 treatments. Among 12 patients with biomarker data, 58% had AXL-positive disease and 75% had PD-L1–positive disease.
Among the 15 patients evaluable for efficacy, 86% of patients with AXL-positive disease achieved a clinical benefit including 1 patient who achieved a partial response. There were no responses among patients whose disease was AXL-negative. The median PFS was 4.73 months compared with 1.87 months among patients with AXL-positive or AXL-negative disease, respectively (hazard ratio [HR], 0.22; 95% CI, 0.04-1.26; P =.066).
Bemcentinib was well tolerated. Among the 73 patients evaluable for safety, the most common grade 3 or higher treatment-related adverse events (TRAEs) were elevations in alanine aminotransferase and aspartate aminotransferase, asthenia, and anemia. There were no reports of grade 5 TRAEs.
Dr Spicer concluded that “bemcentinib-pembrolizumab combined are well tolerated and clinically active in ICI-refractory cAXL-positive NSCLC.” He noted that these results support the further development of bemcentinib.
Disclosure: The presenter disclosed financial relationships with BerGenBio, AstraZeneca, Bristol Myers Squibb, Genmab, GlaxoSmithKline, Lilly, and Roche.
Read more of Cancer Therapy Advisor‘s coverage of the SITC 2020 meeting by visiting the conference page.
Spicer J et al. A PhII study of bemcentinib, a first-in-class selective AXL kinase inhibitor, in combination with pembrolizumab Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting; November 11-14, 2020.