The first patient was dosed with the combination of bemcentinib (BGB324), pembrolizumab (Keytruda), and doublet chemotherapy, for the treatment of patients with first-line non–small cell lung cancer (NSCLC) harboring STK11 mutations (STK11m) in a phase 1b/2a trial (NCT05469178).1
"Approximately 20% of [patients with] non-squamous NSCLC harbor STK11m and do not currently have effective treatment options," Martin Olin, chief executive officer of BerGenBio, stated in the press release. "One specific attribute of this group is that they almost all demonstrate high levels of AXL activation. We are elated to have dosed the first patient in our trial and to continue our evaluation of bemcentinib and its ability to inhibit AXL to revive STK11m NSCLC patients' response to checkpoint inhibitors and chemotherapy."
About the Phase 1b/2a Study
Trial Name: Phase 1b/2a Safety and Tolerability Study of Bemcentinib With Pembrolizumab/Carboplatin/Pemetrexed in Subjects With Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/With a STK11 Mutation
ClinicalTrials.gov Identifier: NCT05469178
Sponsor: BerGenBio ASA
+47 559 61 159, firstname.lastname@example.org
Completion Date: August 11, 2025
In the global, open-label, phase 1b/2a trial, investigators are assessing the safety, tolerability, and efficacy of bemcentinib in combination with current standard of care in untreated advanced/metastatic patients with non-squamous NSCLC patients with STK11 mutations and no actionable mutations.2
Bemcentinib is an anti-AXL inhibitor. In a preclinical model, systemic AXl inhibition using bemcentinib caused the expansion of tumor-associated T cells along with restoring therapeutic response to anti-PD-1 check point inhibitors.
The phase 1b portion of the study will evaluate the safety and feasibility of bemcentinib in combination with pembrolizumab and doublet chemotherapy in patients with treatment-naive advanced or metastatic non-squamous NSCLC, regardless of STK11 status, while the phase 2a expansion portion will assess the efficacy of bemcentinib in this same combination in patients with first-line advanced or metastatic non-squamous NSCLC harboring STK11m. Treatment with bemcentinib will be given once daily until a reason for discontinuation has been met or for up to 2 years,
The trial has an estimated enrollment of 64 patients who must be aged 18 years and older with a histologically confirmed or cytologically confirmed diagnosis of stage IIIb/IIIc or metastatic stage IV non-squamous NSCLC to be included in the study. Patients are required to have not received prior systemic treatment for their advanced or metastatic NSCLC, and they must have measurable disease per RECIST 1.1 criteria as assessed by the investigator.
The primary end points are the number of patients with dose-limiting toxicities in phase 1b, and objective response rate at 6 and 12 months in phase 2a.
The study is currently dosing patients and has an estimated study completion date of August 11, 2025.
"Today, STK11 mutations are correlated with a very poor prognosis for patients suffering from NSCLC. These mutations are widely recognized for their ability to impede the activity of anti-PD-1/L1 therapy,” the trial's lead investigator, Rajwanth Veluswamy, MD, MSCR, an assistant professor of medicine of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai, stated in the press release.1 “My colleagues and I are driven to find a better outcome for this large patient population and are eager to assess bemcentinib's potential in achieving this goal."
1. BerGenBio announces first patient dosed in phase 1b/2a trial evaluating bemcentinib in 1st line non-small cell lung cancer with STK11 mutations. News release. BerGenBio ASA. March 9, 2023. Accessed March 10, 2023. https://bit.ly/3Yy307X
2. A study to investigate the safety, tolerability, and preliminary anti-tumor activity of bemcentinib in combination with pembrolizumab plus pemetrexed and carboplatin in adult participants with untreated non-squamous non-small cell lung cancer. ClinicalTrials.gov. Updated September 9, 2022. Accessed March 10, 2023. https://clinicaltrials.gov/ct2/show/NCT05469178