FDA Accepts BLA for Fixed-Dose Subcutaneous Combination in HER2-Positive Breast Cancer

February 25, 2020

The FDA accepted a biologics license application for the fixed-dose combination of pertuzumab and trastuzumab with hyaluronidase, administered by subcutaneous injection in combination with IV chemotherapy, for the treatment of eligible patients with HER2-positive breast cancer.

The FDA accepted a biologics license application (BLA) for the fixed-dose combination of pertuzumab (Perjeta) and trastuzumab (Herceptin) with hyaluronidase, administered by subcutaneous injection in combination with intravenous (IV) chemotherapy, for the treatment of eligible patients with HER2-positive breast cancer, according to Roche, the developer of the combination.

The BLA is based on results from the phase III FeDeriCa study, which illustrated non-inferior levels of pertuzumab in the blood and comparable efficacy and safety to standard IV infusions of pertuzumab plus trastuzumab and chemotherapy. The FDA set a PDUFA date for October 18, 2020. 

“For more than 2 decades, our medicines have redefined the standard of care for people with HER2-positive breast cancer,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a press release. “Today’s acceptance builds upon our commitment by potentially offering patients a faster way to administer Perjeta and Herceptin. We’re working with the FDA to bring this treatment option to patients as quickly as possible.”

In the multicenter, 2-arm, randomized, phase III study of 500 people with HER2-positive early breast cancer who were being treated in the neoadjuvant and adjuvant settings, the primary endpoint of the study was minimum levels of pertuzumab in the blood during a given dosing interval. Secondary endpoints included safety, minimum levels of trastuzumab in the blood during a given dosing interval, and total pathological complete response (pCR).

The primary endpoint was met, with subcutaneous injection administration of the fixed-dose combination demonstrating non-inferior levels of pertuzumab in the blood during a given dosing interval (Ctrough) when compared to IV administration of the drug. The secondary endpoint of non-inferior Ctrough of trastuzumab was also met. Additionally, rates of total pCR were comparable between the treatment arms. 

The safety profile of the fixed-dose combination in combination with chemotherapy was comparable to that of IV administration of pertuzumab plus trastuzumab and chemotherapy, and no new safety signals were recognized, including no meaningful difference in cardiac toxicity. Moreover, the most common adverse events in both arms were alopecia, nausea, diarrhea, and anemia.

Subcutaneous injection administration of the fixed-dose combination takes approximately 8 minutes for the initial loading dose and approximately 5 minutes for each subsequent maintenance dose. Comparatively, it takes about 150 minutes for infusion of a loading dose of pertuzumab and trastuzumab using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the 2 medicines.

Previously, subcutaneous injection administration has been shown to be strongly preferred by the majority of patients when compared to IV administration of the same treatment, with the most common reason being that administration required less time in the clinic. The company is currently investigating patient preference for subcutaneous injection administration of the fixed-dose combination compared to standard IV administration of pertuzumab and trastuzumab in people with HER2-positive early breast cancer in the PHranceSCa study. Interim results from this phase II study will be presented at a future medical meeting. 

Reference:

FDA accepts Roche’s Biologics License Application for fixed-dose subcutaneous combination of Perjeta and Herceptin for HER2-positive breast cancer [news release]. Basel. Published February 25, 2020. roche.com/media/releases/med-cor-2020-02-25.htm. Accessed February 25, 2020.