A biologics license application has been submitted to the FDA for margetuximab in combination with chemotherapy for the treatment of patients with metastatic HER2-positive breast cancer, according to a press release from MacroGenics, Inc.<br />
A biologics license application (BLA) has been submitted to the FDA for margetuximab (MGAH22) in combination with chemotherapy for the treatment of patients with metastatic HER2-positive breast cancer, according to a press release from MacroGenics, Inc.1
The submission is based on the recent data from the phase III SOPHIA trial (NCT02492711), which compared margetuximab plus chemotherapy (n = 266) with trastuzumab (Herceptin) plus chemotherapy (n = 270) to determine the efficacy of margetuximab in this patient population. Data from this trial were recently presented at the 2019 San Antonio Breast Cancer Symposium (SABCS).
The results of the prespecified second interim OS analysis showed a 26.1-month median OS with margetuximab in the intention-to-treat (ITT) population (95% CI, 18.86-24.05) compared with 19.8 months (95% CI, 17.54-22.28) in patients treated with trastuzumab (HR, 0.89; 95% CI, 0.69-1.13;P= .326).2
Margetuximab plus chemotherapy also significantly improved the overall response rate (ORR) in patients with metastatic HER2-positive breast cancer when compared against trastuzumab and chemotherapy. The median ORR was 25.2% versus 13.7%, respectively, (P= .0006). Patients who received margetuximab also had an improvement in clinical benefit rate, which was 48.1% compared with the 35.6% observed in the trastuzumab group, (P= .0025). The CR rate for the margetuximab was 1.9%, and the PR rate was 23.3%. Additionally, there was a 53.8% incidence of stable disease (SD), and 15% of patients experienced disease progression (PD). In the trastuzumab arm, the CR rate was 1.5%, the PR rate was 12.2%, the SD rate of 58.5%, and a PD rate of 21.1%.
The median duration of response seen in the margetuximab arm was 6.9 months. Response duration was similar in the trastuzumab group at 7 months.
The median PFS, as assessed by the study investigators, was 5.7 months (95% CI, 5.22-6.97) in the margetuximab group versus 4.4 months (95% CI, 4.14-5.45) in the trastuzumab group (HR, 0.71; 95% CI, 0.58-0.86;P= .0006). Overall, the risk of disease progression or death was decreased by 29%.
“As the company’s first BLA submission, this is a key milestone for MacroGenics. We are grateful to the patients who participated in this study, as well as their families, and all involved in developing margetuximab,” said Scott Koenig, MD, PhD, president and CEO of MacroGenics, in a statement. “With this submission, we look forward to working with the Agency to bring margetuximab to appropriate patients. We believe the positive clinical trial results in SOPHIA demonstrate margetuximab’s potential as a treatment option for patients living with this devastating disease.”
Patients in the study were randomized to receive intravenous margetuximab at 15 mg/kg every 3 weeks plus chemotherapy or intravenous trastuzumab with a loading dose of 8 mg/kg followed by 6 mg/kg every 3 weeks plus chemotherapy. There were 4 options for chemotherapy, which were capecitabine, eribulin, gemcitabine, or vinorelbine.
The co-primary end points of the phase III SOPHIA study were PFS assessed by independent radiological review (IRR), OS, and the incidence of grade 3 or higher infusion-related reactions. The secondary end points were investigator-assessed PFS, ORR assessed by IRR, the incidence of all-grade infusion-related reactions.
Patients are aged ≥18 years with histologically proven metastatic or locally advanced relapsed/refractory HER2-positive breast cancer, with some restrictions based on the inclusion/exclusion criteria of the study.
The study is ongoing but no longer recruiting patients. The target completion date for the SOPHIA trial is March 2021. The final OS data from the phase III SOPHIA trial are expected after 385 events. MacroGenics, Inc announced that these data should be available in the second half of 2020.1