– Trodelvy – the First Trop-2-Directed ADC – Delivers a Durable and Clinically Meaningful 3.3 Month Improvement in Median Overall Survival vs. Comparator Chemotherapy in Phase 3 TROPiCS-02 Study –

– Overall Survival Benefit Observed with Trodelvy in Patients with HER2-low (IHC 1+, IHC2+/ISH-) and HER2-IHC0 Status –

FOSTER CITY, CA, USA I June 05, 2023 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced longer-term overall survival (OS) results from the Phase 3 TROPiCS-02 study evaluating Trodelvy® (sacituzumab govitecan-hziy) versus comparator chemotherapy (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- (IHC0, IHC1+, IHC2+/ISH-) metastatic breast cancer who received endocrine-based therapies and at least two chemotherapies. In this exploratory analysis, Trodelvy demonstrated a clinically meaningful improvement in median OS benefit compared to TPC (median OS: 14.5 months vs. 11.2 months; hazard ratio (HR): 0.79; [95% CI: 0.65-0.95]; nominal p=0.0133). These findings will be shared as an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #1003). This abstract has also been selected to be included in the 2023 Best of ASCO® program, which will be held this summer following the ASCO Annual Meeting.

“These longer-term results show the durable overall survival benefit of sacituzumab govitecan over traditional chemotherapy in pre-treated HR+/HER2- metastatic breast cancer,” said Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute, and Associate Professor of Medicine, Harvard Medical School. “At this stage of disease, sequential chemotherapy is common, and benefits may become smaller with subsequent lines of therapy. The potential for a novel agent that may allow patients to live longer is especially meaningful.”

Progression-free survival (PFS) rates for Trodelvy vs. TPC were consistently higher at landmark milestones of 6, 12 and 18 months (45.6% vs. 29.4%, 21.7% vs. 8.4% and 14.4 vs. 4.7%, respectively). Similarly, OS rates for Trodelvy vs. TPC were consistently higher at landmark milestones of 12, 18, and 24 months (60.9% vs. 47.1%, 39.2% vs. 31.7%, and 25.7% vs. 21.1%, respectively). Ninety-two percent of patients in TROPiCS-02 were also eligible for evaluation of OS by HER2 status, as measured by immunohistochemistry (HER2 IHC0, n=217; HER2-low, n=283). Patients treated with Trodelvy demonstrated improved OS versus TPC in both the HER2 IHC0 (median OS: 13.6 months vs. 10.8 months; HR: 0.85 [95% CI: 0.63-1.14]) and HER2-low groups (median OS: 15.4 vs. 11.5 months; HR: 0.75 [95% CI: 0.57-0.97]).

“With these longer-term results in pre-treated HR+/HER2- metastatic breast cancer, Trodelvy has demonstrated proven survival benefit for patients who have had few options until now,” said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. “We believe Trodelvy has the potential to transform outcomes for women across many different types of breast cancers. The survival benefit demonstrated for patients with pre-treated metastatic HR+/HER2- and metastatic triple-negative breast cancer are just the beginning of our clinical development journey. Our ambition is to extend this benefit to more patients, earlier in their treatment journey, where the potential impact is greatest.”

In TROPiCS-02, the most common grade ≥3 treatment emergent adverse events were neutropenia (52%), diarrhea (10%) and fatigue (6%) in the Trodelvy arm, and neutropenia (39%), thrombocytopenia (4%), fatigue (4%) and dyspnea (4%) for those treated with TPC. No new safety signals were identified. No patients treated with Trodelvy in TROPiCS-02 experienced interstitial lung disease (ILD). Trodelvy has a well-characterized safety profile consistent with that in previous studies. In the TROPiCS-02 study, the discontinuation rate due to adverse reactions was 6% for Trodelvy and 4% for patients on single-agent chemotherapy.

Trodelvy was approved in February 2023 by the U.S. Food and Drug Administration for the treatment of adult patients with unresectable locally advanced or metastatic HR+/HER2- breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. The European Medicines Agency has also validated a Type II Variation Marketing Authorization Application for Trodelvy in HR+/HER2- metastatic breast cancer.

Trodelvy is also recommended as a Category 1, preferred treatment for metastatic HR+/HER2- breast cancer by the National Comprehensive Cancer Network® (NCCN®) as defined in the Clinical Practice Guidelines in Oncology (NCCN Guidelines®).i

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- Breast Cancer

Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/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 disease, the five-year relative survival rate is 34%. As patients with HR+/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 cancer who were previously treated with endocrine therapy, CDK4/6 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 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:

  • Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
  • 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.
  • Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see full Prescribing Information, including BOXED WARNING.

About Gilead Sciences

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.


i Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer Version 4.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

SOURCE: Gilead Sciences