Clinical Trials

Date: 2017-05-22

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the 9th World Congress of Melanoma

Company: BergenBio (Norway)

Product: BGB324 in combination with pembrolizumab or dabrafenib+trametinib

Action mechanism:

• AXL inhibitor/ receptor tyrosine kinase inhibitor.  BGB324 is a first-in-class, highly selective small molecule inhibitor of the Axl receptor tyrosine kinase that blocks the epithelial-mesenchymal transition, which is a key driver of metastasis and drug-resistance.. Preclinical in vivo studies have shown that BGB324 has both single agent activity in leukemia and solid tumors and is very effective in preventing and reversing acquired resistance to existing therapies including cytotoxics, protein kinase inhibitors and other targeted therapies.

Disease: melanoma

Therapeutic area: Cancer - Oncology

Country: Norway

Trial details:

• This is an investigator initiated randomized randomized clinical phase 1b/2 clinical trial comparing safety and efficacy of the Axl inhibitor BGB324 in combination with pembrolizumab or dabrafenib+trametinib with that of pembrolizumab or dabrafenib+trametinib alone. Patients with non-resectable stage III or stage IV melanoma will be stratified based on BRAF mutation and tumor load to start dabrafenib+trametinib (BRAF mutation and high tumor load) or pembrolizumab (BRAF wild type or BRAF mutation and low tumor load) in first line. The patients will be randomized 2:1 to receive BGB324 in combination with pembrolizumab or dabrafenib+trametinib or to receive pembrolizumab or dabrafenib+trametinib alone. A 3+3 dose escalation will be performed for the combination of BGB324 and dabrafenib+trametinib. There is a major focus on predictive markers of treatment response evaluated in blood samples and biopsies. (NCT02872259)

Latest news:

• • On October 18, 2017, BerGenBio announced that the clinical trial of BGB324 in combination with either Mekinist® (trametinib) plus Tafinlar® (dabrafenib) or Keytruda® in advanced melanoma have been presented at the 9th World Congress of Melanoma. Dr. Oddbjørn Straume, consultant oncologist at Haukeland University Hospital and Professor at the University of Bergen Centre for Cancer Biomarkers present a poster entitled: A Phase Ib/II randomised study of BGB324 in combination with pembrolizumab or dabrafenib/trametinib in patients with advanced melanoma. The presentation has introduced the trial design and study background as well as present safety data of metastatic melanoma patients treated to date.
• Dr Oddbjørn Straume reported that the recommended Phase 2 dose (RP2D) of BGB324 in combination with trametinib and dabrafenib had been established. In addition, Dr Straume presented early data demonstrating that BGB324 is well tolerated in combination with either dabrafenib and trametinib or pembrolizumab.
• Patient recruitment in all three arms of the Phase 2 study is ongoing and seeks to demonstrate safety and efficacy of BGB324 in combination with pembrolizumab or dabrafenib and trametinib in the first-line and second line setting. A parallel biomarker study is ongoing in collaboration with MIT and Harvard Medical School.
• • On May 22, 2017, BerGenBio announced that the first patients have been dosed and continue on therapy in a Phase I/II randomised trial evaluating the addition of BerGenBio’s highly selective, potent and orally bio-available AXL inhibitor BGB324 to standard of care treatments in patients with advanced, non-resectable or metastatic melanoma. The trial, which is sponsored by Haukeland University Hospital (Bergen, Norway), with the support of BerGenBio, plans to enrol up to 92 melanoma patients from several Norwegian hospitals.
• Patients recruited into the study will be randomised based on their tumour load and BRAF mutational status* to receive either:
• • Pembrolizumab (Keytryda®) +/- BGB324, or• Dabrafenib (Tafinlar®) and trametinib (Mekinist®) +/- BGB324
• Endpoints of the study are objective response rate as well as progression free survival, duration of response and overall survival.
• In parallel with the clinical trial, leading Norwegian experts in treating melanoma together with collaborators at Massachusetts Institute of Technology and Harvard Medical School (Boston, USA) are conducting a comprehensive programme of explorative biomarker analyses.

Is general: Yes