U.S. FDA Approves Trodelvy® in Pre-treated HR+/HER2- Metastatic Breast CancerHR+/HER2- Metastatic Breast Cancer

03 Feb 2023
pipelinereview.com
Clinical ResultDrug ApprovalPhase 3Priority ReviewASCO
-- First Trop-2 Directed ADC to Demonstrate Overall Survival Benefit in HR+/HER2- Metastatic Breast CancerHR+/HER2- Metastatic Breast Cancer Patients who had Received Prior Endocrine-based Therapy and at Least Two Chemotherapies --
-- Trodelvy has Now Improved Survival in both Pre-Treated HR+/HER2- Metastatic Breast CancerHR+/HER2- Metastatic Breast Cancer and in Second-Line Metastatic Triple-Negative Breast Cancer --
FOSTER CITY, CA, USA I February 03, 2023 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced the U.S. Food and Drug Administration (FDA) has approved Trodelvy® (sacituzumab govitecan-hziy) for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. The approval is based on statistically significant and clinically meaningful progression-free survival and overall survival data from the Phase 3 TROPiCS-02 study. Trodelvy is now also recommended as a Category 1, preferred treatment for metastatic HR+/HER2- breast cancerHR+/HER2- breast cancer by the National Comprehensive Cancer Network® (NCCN®) as defined in the Clinical Practice Guidelines in Oncology (NCCN Guidelines®)i.
“Despite decades of advances, people living with pre-treated HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer need new treatment options. Nearly all people with this type of breast cancer will eventually develop resistance to endocrine-based therapies and progress on available chemotherapies,” said Hope S. Rugo, MD, Professor of Medicine and Director, Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center, U.S. and principal investigator of the TROPiCS-02 study. “This approval is significant for the breast cancer community. We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than three months with a quality of life benefit for these women is exceptional.”
In the TROPiCS-02 study, Trodelvy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit of 3.2 months versus comparator single-agent chemotherapy (treatment of physician’s choice; TPC) (median OS: 14.4 months vs. 11.2 months; hazard ratio [HR]=0.79; 95% CI: 0.65-0.96; p=0.02). Trodelvy also demonstrated a 34% reduction in risk of disease progression or death (median PFS: 5.5 versus 4.0 months; HR: 0.66; 95% CI: 0.53-0.83; p=0.0003). Three times as many people treated with Trodelvy were progression free at one year versus those treated with chemotherapy (21% versus 7%). In a post-hoc analysis, data demonstrated Trodelvy’s efficacy across HER2-low and IHC0 status in pre-treated metastatic breast cancer patients in the TROPiCS-02 trial.
Trodelvy also significantly improved additional secondary endpoint measures, including objective response rate and time to deterioration (TTD) assessed by the Global Health Status/Quality of Life and Fatigue scale per EORTC-QLQ-C30. No statistically significant difference in TTD in Pain Scale was observed.
“The FDA approval is an important step forward for both women and men living with metastatic breast cancer, especially for those individuals whose tumor is no longer responding to endocrine-based therapies and who are facing a poor prognosis,” said Laura Carfang, Executive Director, SurvivingBreastCancer.org. “We need to combat this terrible disease, and all options that potentially slow its progress and extend life for those living with metastatic breast cancer are welcomed.”
“We are pleased that Trodelvy could now provide new hope for people living with pre-treated HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer, building on the transformative role that Trodelvy is already playing for people with metastatic triple-negative breast cancer,” said Daniel O'Day, Chairman and Chief Executive Officer, Gilead Sciences. “We thank the physicians, patients and their families who put their trust in the TROPiCS-02 study and helped make this milestone possible.”
The safety profile for Trodelvy was consistent with prior studies, with no new safety signals identified in this patient population. In TROPiCS-02 the most frequent serious adverse reactions (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes. No patients treated with Trodelvy experienced interstitial lung disease.
This review by the FDA was conducted under Project Orbis and granted Priority Review.
The European Medicines Agency has also validated a Type II Variation Marketing Authorization Application for Trodelvy in HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer.
Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.
About HR+/HER2- Metastatic Breast CancerHR+/HER2- Metastatic Breast Cancer
Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancerHR+/HER2-) breast cancer is the most common type of breast cancer and accounts for approximately 70% of all new cases. Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic diseaseHR+/HER2- metastatic disease, the five-year relative survival rate is 30%. As patients with HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy. In this setting, it is common to receive multiple lines of chemotherapy regimens over the course of treatment, and the prognosis remains poor.
About the TROPiCS-02 Study
The TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physicians’ choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitorCDK4/6 inhibitor and two to four lines of chemotherapy for metastatic disease. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures. In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test. More information about TROPiCS-02 is available at https://clinicaltrials.gov/ct2/show/NCT03901339.
About Trodelvy
Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.
Trodelvy is approved in more than 40 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Trodelvy is also approved in the U.S. to treat certain patients with pre-treated HR+/HER2- metastatic breast cancerHR+/HER2- metastatic breast cancer and has an accelerated approval for treatment of certain patients with second-line metastatic urothelial cancer; see below for full indication statements.
Trodelvy is also being developed for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.
U.S. Indications for Trodelvy
In the United States, Trodelvy is indicated for the treatment of adult patients with:
Please see full Prescribing Information, including BOXED WARNING.
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.
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