Everest Medicines‘ U.S.-based licensing partner Immunomedics earlier today confirmed that the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) submitted for sacituzumab govitecan-hziy (marketed as Trodelvy™ in the United States) for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease.

The approval came almost one and a half months ahead of its U.S. Prescription Drug User Fee Act (PDUFA) date of June 2, 2020.

Sacituzumab govitecan is an antibody-drug conjugate (ADC) that links SN-38, the active metabolite of irinotecan, via a hydrolyzable linker to a humanized monoclonal antibody against the human trophoblast cell-surface antigen 2 (Trop2).

Trop2 is a membrane antigen that is frequently over-expressed in many common epithelial cancers. Sacituzumab govitecan delivers high concentrations of the SN-38 payload to tumors.

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Metastatic triple-negative breast cancer (TNBC) is a highly aggressive disease and accounts for approximately 15% of all breast cancer types worldwide. [1][2][3]

The median age of breast cancer diagnoses tends to be younger in China than in western countries, and the percentage of TNBC molecular subtype has increased to 20.3% in the past 10 years. TNBC cells lack sufficient estrogen, progesterone, or HER2 receptor expression to benefit from the use of hormonal or HER2-directed therapy. Overall survival among patients with this form of breast cancer has not changed in the past 20 years, which highlights the need for advances in therapeutic options for these patients.[4][5][6][7][8]

License agreement
In April 2019, Everest Medicines entered into an exclusive license agreement to develop, register, and commercialize sacituzumab govitecan in Greater China, South Korea, and certain Southeast Asian countries and territories.

On April 22, 2020, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of People’s Republic of China approved the Clinical Trial Application (CTA) of sacituzumab govitecan, which will allow Everest Medicines to initiate a pivotal Phase III clinical trial of this investigational therapy for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease in China.

Everest Medicines confirmed that it plans to initiate this trial in the first half of 2020.

The FDA previously granted Breakthrough Therapy Designation and Priority Review to sacituzumab govitecan, which was approved under the Accelerated Approval Program based on the objective response rate (ORR) and duration of response (DoR) observed in a single-arm, multicenter, Phase II study conducted in 108 patients.

Immunomedics’ confirmatory Phase III ASCENT study (NCT02574455) was recently halted by the independent Data Safety Monitoring Committee for “compelling evidence of clinical benefit across multiple endpoints.”

First approved ADC for mTNBC
“Sacituzumab govitecan is the first ADC approved therapy for metastatic TNBC worldwide. mTNBC is a highly aggressive cancer with limited existing therapeutic options and an overall survival rate that has remained unchanged for two decades. This important approval provides clinicians with a novel treatment option for treating patients with this devastating disease,” stated Professor Binghe Xu, M.D., Ph.D., Chief of the National Clinical Research Center for Anti-Cancer Drugs and Principle Investigator of Trodelvy China Registration Study.

“As clinicians, we look forward to the initiation of a clinical trial in China to help advance this important drug for Chinese patients as quickly as possible.”

“We are excited to continue our efforts to potentially bring Trodelvy to greater China and other select Asian countries and territories. The US approval of Trodelvy validates and has the potential to accelerate Everest’s clinical development in China and Asia. We are committed to broadening the potential use of this important new medicine across other oncology indications in collaboration with our partner, Immunomedics, as we continue to focus our work to address disease areas with high unmet need in the Asia region,” said Yang Shi, MD, Chief Medical Officer for Oncology and Immunology at Everest Medicines.

A growing number of patients
“As the incidence of triple-negative breast cancer continues to rise in China, many patients are left with no therapeutic options after second-line chemotherapy treatments. These patients are in urgent need of a breakthrough therapy with the potential to extend their lives. I am very excited to learn that sacituzumab govitecan has been approved by the FDA and look forward to the possibility of making this medicine available to benefit breast cancer patients in China,” noted professor Anli Shi, President of Beijing Love Book Cancer Foundation and President of Cancer Rehabilitation Society of CACA (CRS).

“The approval of Trodelvy by the US FDA is great news for patients with mTNBC and further validation of the Everest Medicines model to in-license global innovation for development in China and Asia. With our recent CTA approval in China we are working to quickly bring this medicine to Chinese patients who suffer from mTNBC as our development team doubles-down on their efforts to accelerate clinical development in China,” noted Kerry Blanchard, M.D., Ph.D., the Chief Executive Officer Everest Medicines.

Clinical trial
ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT) – NCT02574455

References
[1] DeSantis CE, Fedewa SA, Goding Sauer A, Kramer JL, Smith RA, Jemal A. Breast cancer statistics, 2015: convergence of incidence rates between black and white women. CA Cancer J Clin 2016;66:31-42.
[2] Plasilova ML, Hayse B, Killelea BK, Horowitz NR, Chagpar AB, Lannin DR. Features of triple-negative breast cancer: analysis of 38,813 cases from the National Cancer Database. Medicine (Baltimore) 2016;95(35):e4614.
[3] Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ ethnicity, poverty, and state. J Natl Cancer Inst 2015;107(6):djv048.
[4] Khosravi-Shahi P, Cabezón-Gutiérrez L, Custodio-Cabello S. Metastatic triple-negative breast cancer: optimizing treatment options, new and emerging targeted therapies. Asia Pac J Clin Oncol 2018;14: 32-9.
[5] Brufsky A, Valero V, Tiangco B, et al. Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial. Breast Cancer Res Treat 2012;133: 1067-75.
[6] Perez EA, Patel T, Moreno-Aspitia A. Efficacy of ixabepilone in ER/PR/HER2- negative (triple negative) breast cancer. Breast Cancer Res Treat 2010;121:261-71.
[7] Park IH, Im SA, Jung KH, et al. Randomized open-label phase III trial of irinotecan plus capecitabine versus capecitabine monotherapy in patients with metastatic breast cancer previously treated with anthracycline and taxane: PROCEED trial (KCSG BR 11-01). Cancer Res Treat 2019; 51:43-52.
[8] Twelves C, Awada A, Cortes J, et al. Subgroup analyses from a phase 3, open-label, randomized study of eribulin mesylate versus capecitabine in pretreated patients with advanced or metastatic breast cancer. Breast Cancer (Auckl) 2016;10:77- 84