Margetuximab plus chemotherapy showed positive results in a second pre-specified interim overall survival analysis for the phase 3 SOPHIA study.
Adding margetuximab to chemotherapy prolonged overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, according to results from an interim analysis of a phase 3 study.
Margetuximab is an investigational monoclonal antibody that targets the HER2 oncoprotein, which is expressed by tumor cells in breast cancer. Similar to trastuzumab, margetuximab has HER2-binding and antiproliferative effects.
For patients with relapsed or refractory HER2-positive disease, ongoing HER2 blockade is recommended, but there is currently no approved therapy for third-line treatment and beyond.
The phase 3 SOPHIA study is evaluating margetuximab plus chemotherapy compared with trastuzumab plus chemotherapy in 536 patients with HER2-positive metastatic breast cancer. Patients in the study must have received at least 2 prior lines of anti-HER2-directed therapy in the metastatic setting, or in the case of having received (neo)adjuvant pertuzumab, at least 1 prior line of anti-HER2-directed therapy, and who have received at least 1 and no more than 3 prior lines of therapy overall in the metastatic setting.
The updated data are from the second pre-specified interm OS analysis based on 270 events.
For the study, 266 patients received margetuximab given intravenously at 15 mg/kg every 3 weeks and 270 patients received intravenous trastuzumab at 6 mg/kg or 8 mg/kg for loading dose. Both groups also received 1 of 4 chemotherapy agents (capecitabine, eribulin, gemcitabine, or vinorelbine) given at the standard dose.
In the intent-to-treat (ITT) population, the median OS of patients treated with margetuximab plus chemotherapy was extended by 1.8 months compared with that of patients who received trastuzumab and chemotherapy (21.6 months versus 19.8 months; hazard ration [HR]=0.885; 95% CI: 0.693-1.130; p=0.326).
Additionally, among the approximately 85% of patients carrying a CD16A 158F allele variation, the median OS was prolonged by 4.3 months in the margetuximab group compared with thr trastuzumab group (23.7 months versus 19.4 months; HR-0.793; 95% CI: 0.607-1.035; p=0.087), according to the study.
Of the approximately 15% of patients who were homozygous for the CD16A 158V allele, the trastuzumab arm performed better than the margetuximab arm, the study found.
The safety profile of margetuximab plus chemotherapy was generally tolerable and comparable with that of trastuzumab plus chemotherapy. Infusion-related reactions were more common with margetuximab treatment than with trastuzumab and were mostly grade 1 or 2 and associated with the first dose.
The final pre-specified OS analysis is planned after 385 events have accrued, which is projected to occur in 2020, according to MacroGenics. The first sequential primary endpoint of progression-free survival in the ITT population was achieved, with statistical significance as previously reported.
Detailed results from the second interim OS analysis were presented during an oral session at the 2019 San Antonio Breast Cancer Symposium.
MacroGenics Announces Second Interim Overall Survival Data from Phase 3 SOPHIA Study of Margetuximab in Patients with HER2-Positive Metastatic Breast Cancer [news release]. MacroGenics' website. http://ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-second-interim-overall-survival-data-phase. Accessed October 24, 2019.