Puma Submits sNDA for Neratinib Combo Therapy for HER2-Positive Metastatic Breast Cancer

Puma Biotechnology submitted a supplemental New Drug Application to the FDA for neratinib (Nerylnx) in combination with capecitabine for the treatment of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

Puma Biotechnology is seeking FDA approval for neratinib (Nerylnx) in combination with capecitabine for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, according to a press release.

The company submitted a supplemental New Drug Application (sNDA) to the FDA for this indication in patients who have failed 2 or more prior lines of HER2-directed treatments.

Neratinib was previously approved by the FDA in 2017 for the extended adjuvant treatment of adults with early-stage HER2-overexpressed/amplified breast cancer following adjuvant trastuzumab-based therapy.

The submission of the current sNDA is based on data from the phase 3 NALA clinical trial, which evaluated neratinib plus capecitabine versus lapatinib (Tykerb) plus capecitabine in patients with third-line HER2-positive metastatic breast cancer.

In the study, 621 patients were randomized to receive either neratinib plus capecitabine or lapatinib plus capecitabine, with the co-primary endpoints being centrally confirmed progression-free survival (PFS) and overall survival (OS).

According to the findings, treatment with neratinib plus capecitabine demonstrated a statistically significant improvement in centrally confirmed PFS (hazard ratio=0.76, p=0.0059) compared with treatment with lapatinib plus capecitabine.

In a prespecified analysis, the mean PFS for patients was 8.8 months for patients treated with neratinib plus capecitabine and 6.6 months for those treated with lapatinib plus capecitabine. Further, the prespecified means analysis showed a median OS of 21 months for patients treated with neratinib plus capecitabine compared with 18.7 months for lapatinib plus capecitabine.

Overall, the primary analyses demonstrated that neratinib plus capecitabine demonstrated improvement in OS compared with the other treatment group. The median OS for patients treated with neratinib plus capecitabine was 21 months compared with 18.7 months for patients treated with lapatinib plus capecitabine.

Additionally, the overall cumulative incidence for intervention for central nervous system (CNS) metastases at 54 months was 22.8% among patients in the neratinib plus capecitabine group and 29.2% of patients in the lapatinib plus capecitabine group. The data also demonstrated that neratinib plus capecitabine resulted in a longer median duration of response (8.54 months) compared with lapatinib plus capecitabine (5.55 months).

“We are very pleased to announce this important regulatory milestone,” Alan H. Auerbach, chief executive officer and president of Puma, said in a statement. “Although the use of HER2-directed agents in the metastatic setting has positively impacted the treatment of the disease in the first- and second-line settings, patients with HER2-positive metastatic breast cancer who have progressed on 2 or more prior treatments continue to need additional treatment options. We look forward to working with the FDA during its review of this submission.”

Reference

Puma Biotechnology Submits a Supplemental New Drug Application to US FDA for Neratinib to Treat HER2-Positive Metastatic Breast Cancer [news release]. Puma Biotechnology. https://www.pumabiotechnology.com/pr20190701.html. Accessed July 1, 2019.