The randomized phase IIb METRIC trial could possibly pave the way for the first FDA approval for a targeted therapy for patients with triple-negative breast cancer. <br />
The METRIC study, which has recently completed accrual, enrolled patients diagnosed with metastatic TNBC, adequate bone marrow, liver, and renal function, and confirmed expression of gpNMB. This was determined by submitting a tissue sample from the advanced disease setting for analysis. Additionally, patients received no more than 2 prior chemotherapy treatments, including an anthracycline and a taxane.
Currently, the only approved treatment for patients in this space is chemotherapy, which has created excitement around the METRIC trial and the potential that glembatumumab vedotin has shown thus far. This antibody-drug conjugate is a novel approach designed to target a very difficult-to-treat patient population.
Prior to the METRIC study, glembatutmumab vedotin was investigated in the randomized phase II EMERGE study, which showed an objective response rate (ORR) of 6% with the antibody-drug conjugate versus 7% for investigator-selected chemotherapy in all comers; however, response rates reached 30% in patients with gpNMB expression in ≥25% of tumor cells.1Response rates were also significantly improved in patients with TNBC, reaching 18% in this population overall, and 40% when considering those with gpNMB-overexpressing TNBC.
In the METRIC trial, 327 women with high levels of gpNMB expression were randomized 1:1 to glembatumumab vedotin or standard capecitabine. About 40% of TNBC and approximately 20% of breast cancers overall exhibit overexpression of gpNMB. Overexpression of gpNMB has historically been associated with reduced survival in breast cancer, small cell lung cancer, and glioblastoma.
The primary endpoint of the METRIC trial is progression-free survival (PFS), and a final data analysis will occur after 203 PFS events. Secondary endpoints include ORR, duration of response (DOR), overall survival (OS), and adverse events.
Enrollment in the trial was completed in late August 2017, announced the company conducting the trial, Celldex Therapeutics. The company predicts topline results for the primary endpoint of PFS will be available in the middle of 2018.
"We are extremely grateful to the METRIC investigators and the patients and families who supported this trial," Anthony Marucci, co-founder, president and chief executive officer of Celldex Therapeutics, said in a statement. "Patients with triple-negative breast cancer have very limited treatment options. We believe glemba holds significant promise as a potential new targeted treatment for patients with this devastating disease and look forward to topline data, likely in the second quarter of 2018."
Many are focused on TNBC both because of the high unmet need and the progress that is being made. In addition to the METRIC study, trial results investigating immunotherapy are highly anticipated for this patient population. This is partly due to the high mutational load that can be found with triple-negative tumors.
1. Yardley DA, Weaver R, Melisko ME, et al. EMERGE: a randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB-expressing breast cancer.J Clin Oncol.2015;33(14):1609-1619. doi: 10.1200/ JCO.2014.56.2959.