On February 15, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported topline data from BGBC008, a phase 2 trial evaluating its lead compound bemcentinibin combination with MSD’s anti-PD-1 therapy pembrolizumab in 2L+ Non-Small Cell Lung Cancer (NSCLC) patients (Press release, BerGenBio, FEB 15, 2023, View Source [SID1234627251]).

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BGBC008 Topline Data

The open-label, multi-center, single arm, multi-cohort, international phase 2 trial conducted in collaboration with MSD (Merck and Co., Inc. Rahway, NJ, USA), enrolled 90 evaluable patients with disease progression at study entry, who had received at least one prior line of chemotherapy, immunotherapy, or the combination. Enrolled patients received the combination of bemcentiniband pembrolizumab until disease progression as assessed by investigators. Topline results from the total evaluable population:

A clinically meaningful survival benefit and evidence of disease control was demonstrated with bemcentinibin combination with pembrolizumab regardless of prior therapy, providing a median overall survival (mOS) of 13.0 months (95% CI: 10.1, 16.7), median progression free survival (mPFS) of 6.2 months (95% CI: 4.6, 9.8), disease control rate (DCR) of 51.1% (95% CI: 40.3, 61.8) and overall response rate (ORR) of 11.1% (95% CI: 6.2, 18.1).
A significant (p-value < 0.05) and clinically meaningful improvement in mOS based on AXL tumor proportion score (TPS) was observed. Patients with AXL TPS > 5 (46% of evaluable patients) achieved a mOS of 14.8 months (95% CI: 12.4, 29.6) compared to patients with AXL TPS < 5, who achieved a mOS of 9.9 months (95% CI: 6.7, 17.4). In addition, patients with an AXL TPS > 5 had a mPFS of 8.7 months (95% CI: 6.0, 14.8) compared to 4.6 months (95% CI: 2.7, 8.1) for patients with AXL TPS < 5. The ORR for AXL TPS > 5 was 21.9%.
The observed mOS was similar regardless of patient PD-L1 status.
Treatment with bemcentinib in combination with pembrolizumab was well-tolerated.
"We are very encouraged by the topline data" said Martin Olin, Chief Executive Officer of BerGenBio. "Treatment with bemcentinib in combination with pembrolizumab demonstrated long survival benefit and sustained disease control, particularly in patients with AXL TPS > 5, substantiating the relevance of AXL as a target and bemcentinib’s selective inhibition capabilities in NSCLC. Notably, the survival benefit was observed regardless of PD-L1 status. The data support our ongoing phase 1b/2a trial in 1L STK11m NSCLC patients, of whom approximately 80% have AXL expression. This subgroup of NSCLC represents more than 30,000 patients in the US and five largest European countries, for whom there is currently no effective targeted therapy available."

James Spicer, PhD, FRCP, Professor of Experimental Cancer Medicine at King’s College London and Principal Investigator of the BGBC008 trial, remarked, "The reported data shows that the combination of bemcentinib and pembrolizumab is well-tolerated in patients with NSCLC, and is particularly active in patients with tumour AXL expression. Other evidence suggests that current therapies are less effective in NSCLC with loss of the tumour suppressor gene STK11, and that AXL inhibition can restore susceptibility. Further investigation is warranted to confirm the role of AXL inhibition in STK11-mutated NSCLC patients, who are under-served by currently available therapeutic options."

The Company plans to present further details of the BCBG008 trial at an upcoming medical conference.

First-Line STK11m NSCLC Trial (BGBC016)

BerGenBio is studying bemcentinibin a global, open-label, phase 1b/2a trial evaluating bemcentinibin combination with the current standard of care of pembrolizumab and platinum doublet chemotherapy, for the treatment of 1L NSCLC patients with mutations in the STK11 gene. More than 30,000 NSCLC patients (US and EU5) harbor STK11 mutations which are associated with poor prognosis with currently available therapies. The Company believes that STK11 mutations create a severely immunosuppressed tumor microenvironment associated with AXL expression and activation, resulting in the development of drug resistance, immune evasion, and metastases.