#United States #FDA Approval #Sacituzumab #Foster City #Metastatic Breast Cancer

FDA Approves Sacituzumab Govitecan for TNBC

On June 24, Gilead Sciences announced that the U.S. Food and Drug Administration (FDA) has granted approval for Sacituzumab Govitecan, a first-in-class antibody-drug conjugate targeting TROP-2, to be used as a first-line treatment for adults with locally advanced or metastatic triple-negative breast cancer (TNBC). This approval positions Sacituzumab Govitecan as a valuable monotherapy for patients who are unsuitable for treatment with PD-1/PD-L1 inhibitors, as well as in combination with pembrolizumab (Keytruda) for PD-L1 positive patients.

Dr. Sara Tolaney, the Director of the Breast Oncology program at Dana-Farber Cancer Institute and the lead investigator of the ASCENT-03 and ASCENT-04 trials, emphasized the importance of initial treatment options for metastatic TNBC patients. She stated, "The approval is encouraging news for patients and the clinical community, providing a new option that can transform initial treatment for all patients regardless of PD-L1 status."

The FDA's decision was based on the statistically significant and clinically meaningful progression-free survival (PFS) results from both the ASCENT-03 and ASCENT-04 trials. In these studies, Sacituzumab Govitecan demonstrated a substantial reduction in the risk of disease progression or death as a first-line treatment for metastatic TNBC. The ASCENT-03 trial showed that monotherapy with Sacituzumab Govitecan reduced this risk by 38% compared to chemotherapy for patients not eligible for PD-1/PD-L1 therapy, while the ASCENT-04 trial presented a 35% risk reduction for patients receiving Sacituzumab Govitecan along with Keytruda compared to chemotherapy plus Keytruda.

Both trials also suggested that the Sacituzumab Govitecan-based regimen offered a longer duration of response. The median duration of response (DOR) was reported at 12.2 months for the ASCENT-03 trial and 16.5 months for the ASCENT-04 trial, outperforming the 7.2 month and 9.2 month durations observed in the chemotherapy arms, respectively.

Ricki Fairley, CEO and co-founder of TOUCH, The Black Breast Cancer Alliance, expressed how significant this new first-line treatment option is for the TNBC community, which has often faced limited treatment opportunities. "For many women who are relatively young and busy with life, being diagnosed with TNBC can lead to poor prognoses. It's crucial that they have access to promising treatment options like Sacituzumab Govitecan, which can be used even without the combination of Keytruda."

Dietmar Berger, M.D., PhD, Chief Medical Officer of Gilead Sciences, added, "This FDA approval provides a new standard of care for the most aggressive types of breast cancer, having limited treatment options for previous decades. Sacituzumab Govitecan is now available as a formidable backbone therapy for patients requiring first-line treatment for metastatic TNBC."

The findings from ASCENT-03 and ASCENT-04 have led to Sacituzumab Govitecan receiving a Category 1 recommendation as a treatment option for first-line therapy in PD-L1 positive and negative metastatic TNBC patients according to the National Comprehensive Cancer Network (NCCN) guidelines. Furthermore, it holds Category 1 recommendations for second-line treatments for TNBC patients with treatment histories as well.

Sacituzumab Govitecan is already established among health care professionals, having been administered to over 75,000 patients across more than 60 countries over the past six years. It stands out as the only ADC that has shown significant survival benefits for both metastatic TNBC after second-line treatment and for hormone receptor-positive, HER2-negative metastatic breast cancer cases. It has exhibited positive results in four Phase III trials targeting HER2-negative metastatic breast cancer patients.

Summary of Sacituzumab Govitecan

Sacituzumab Govitecan is designed to target TROP-2, a cell surface antigen expressed in more than 90% of breast and lung cancers. Its payload, SN-38, is a topoisomerase I inhibitor linked to an antibody through a unique hydrolysable linker, providing potent activity both at the TROP-2 positive cells and in the tumor microenvironment through a bystander effect.

Currently, Sacituzumab Govitecan is approved as a drug for treating TNBC in second-line therapies in over 60 countries, as well as for previous treatment histories of hormone receptor-positive, HER2-negative breast cancers in more than 50 countries. Gilead is actively pursuing approval submissions based on the ASCENT-03 and ASCENT-04 results worldwide.

In ongoing Phase III trials, the drug continues to be evaluated for various cancers exhibiting high TROP-2 expression, including in combinations with pembrolizumab, for early intervention treatments in TNBC as well as lung and gynecological cancers.

Important Safety Information

The approval of Sacituzumab Govitecan comes with important safety information regarding potential adverse effects such as neutropenia and diarrhea. It could also lead to severe allergic reactions that may necessitate pre-treatment preparations. Patients must be carefully monitored for potential side effects, especially in high-risk cases, ensuring both clinical efficacy and patient safety in the administration of this groundbreaking treatment. Studies have indicated that adverse effects may include nausea and vomiting, presenting with significant incidences across the patient population, and necessitating the inclusion of supportive therapies to manage these effects.