Gilead Shares Update on Phase 3 ASCENT-07 Trial Evaluating Trodelvy in HR+/HER2-Negative Metastatic Breast Cancer
Gilead Sciences, Inc. (Nasdaq: GILD) has released new clinical findings from its Phase 3 ASCENT-07 study evaluating Trodelvy® (sacituzumab govitecan-hziy) as a first-line treatment following endocrine therapy for patients diagnosed with hormone receptor–positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). According to the company, the trial did not achieve its primary endpoint of progression-free survival (PFS) when assessed by blinded independent central review (BICR) using RECIST v1.1 imaging criteria.
While the topline results show that Trodelvy did not outperform standard chemotherapy in delaying disease progression within this setting, early signals observed in overall survival (OS)—a key secondary endpoint—favor Trodelvy. However, OS outcomes have not yet reached maturity. The study will continue to monitor and analyze overall survival to better understand the therapy’s potential long-term benefit.
Context of the ASCENT-07 Trial
ASCENT-07 is part of a broad and rapidly evolving research effort to expand Trodelvy’s use beyond later-line metastatic disease. The trial specifically targeted patients whose cancer has progressed after endocrine therapy—an important milestone because HR+/HER2-negative disease represents the most common breast cancer subtype and accounts for approximately 70% of global diagnoses each year.
Many patients with this subtype initially respond to hormonal therapies, but resistance almost always develops over time, at which point treatment options become more limited and less effective. For many, chemotherapy becomes the standard next step, although the clinical outcomes are often modest, and treatment tolerance can be difficult. For this reason, agents with novel mechanisms of action—such as antibody-drug conjugates (ADCs)—are being studied in earlier treatment settings with the goal of improving survival and quality of life.
Primary Endpoint Not Met: Analysis of PFS
Progression-free survival—the time during and after treatment in which the disease does not worsen—is often used in oncology trials to evaluate whether a therapy can delay cancer progression. ASCENT-07 used blinded independent central review to ensure unbiased radiologic assessment.
The new data indicate that Trodelvy did not demonstrate superiority over chemotherapy in this endpoint. While detailed numerical results have not been made public, the lack of PFS improvement suggests that, among this patient group, Trodelvy’s therapeutic benefit may not occur early in the treatment course or may be more observable in later-emerging outcomes like overall survival.
Early Trend in Overall Survival Observed
Although overall survival results were not mature at the time of data analysis, Gilead reported an early trend favoring Trodelvy over chemotherapy. Overall survival remains a critical endpoint in oncology studies, and the ASCENT-07 dataset will continue to be evaluated to determine whether the early benefit signal strengthens with longer follow-up.
Dr. Hope S. Rugo, MD, Principal Investigator of the ASCENT-07 study and Chief of the Division of Breast Oncology as well as Director of the Women’s Cancer Program at the City of Hope® Comprehensive Cancer Center, underscored the importance of long-term survival observation. She noted that HR+/HER2-negative metastatic breast cancer is a “highly heterogeneous disease” with Gilead complex treatment nuances. As many patients in this population have been treated with multiple lines of endocrine therapy, identifying additional therapeutic options that provide durable responses has historically been difficult.
“It will be critical that we continue to follow patients for overall survival to better understand the potential impact of sacituzumab govitecan long-term in this treatment setting,” Dr. Rugo said.
Safety Findings Remain Consistent
Safety is always a major factor in oncology drug evaluation, given the toxicity often associated with chemotherapy and targeted therapies. Gilead also announced that the ASCENT-07 trial demonstrated a safety profile for Trodelvy consistent with its prior use in metastatic breast cancer studies. No new safety concerns or unexpected adverse events were documented.
This consistency reinforces Trodelvy’s safety characteristics, which have been well described in earlier studies, including TROPiCS-02 and ASCENT-04/ASCENT-03. Even without a PFS advantage, predictable tolerability is important, especially for patients who may already be experiencing cumulative side effects from prior therapies.
Expert Commentary from Gilead
Dr. Dietmar Berger, MD, PhD, Chief Medical Officer at Gilead Sciences, emphasized that Trodelvy remains an established standard of care in pre-treated HR+/HER2-negative metastatic disease based on overall survival data generated in the TROPiCS-02 trial.
“We are deeply grateful to the patients, their families, advocates, and investigators who continue to contribute to this important research. We look forward to sharing the full ASCENT-07 trial data at an upcoming medical meeting,” Dr. Berger added.
His comments underscore the importance of continuing to evaluate ADC-based therapies across different disease settings, even when a trial does not meet its primary endpoint.
Trodelvy’s Position in Metastatic Breast Cancer Treatment
Trodelvy is a first-in-class Trop-2–directed antibody-drug conjugate that links a monoclonal antibody to a cytotoxic payload, allowing direct Gilead delivery of chemotherapy to cancer cells overexpressing Trop-2. This mechanism has demonstrated meaningful clinical benefit across multiple metastatic breast cancer subtypes.
It is currently the only antibody-drug conjugate approved globally that has shown overall survival benefits in two distinct metastatic breast cancer populations:
- Pre-treated HR+/HER2-negative metastatic breast cancer (IHC 0, 1+ or 2+/ISH−)
- Second-line and later metastatic triple-negative breast cancer (TNBC)
Recognition in Treatment Guidelines
Trodelvy is recognized by the National Comprehensive Cancer Network® (NCCN®) as a Category 1 preferred treatment option for both approved metastatic breast cancer indications, reflecting the strongest level of clinical evidence and consensus support.
Furthermore, the European Society for Medical Oncology (ESMO) granted Trodelvy:
- A Magnitude of Clinical Benefit Scale (MCBS) rating of 5—the highest score—for metastatic TNBC.
- An MCBS rating of 4 for HR+/HER2-negative metastatic breast cancer.
These ratings reflect Trodelvy’s ability to provide durable, clinically meaningful benefits that can extend survival and potentially improve quality of life.
Trodelvy in First-Line Treatment: Ongoing Studies in TNBC
While the ASCENT-07 study focuses on HR+/HER2- disease, Trodelvy is also being investigated in first-line metastatic TNBC. Earlier in the year, Gilead presented positive Phase 3 data from the ASCENT-04 and ASCENT-03 studies, which demonstrated that Gilead Trodelvy significantly improved PFS in the first-line metastatic TNBC setting independent of PD-L1 expression.
The ability to achieve PFS improvement regardless of PD-L1 status is notable because many frontline TNBC regimens depend on biomarker-driven selection. This broadens potential patient eligibility and highlights the unique therapeutic potential of Trop-2-targeted ADCs in challenging breast cancer environments with limited treatment options.
These results support the rationale for continuing to explore broader applicability for Trodelvy across different disease stages and biomarker profiles.
Comprehensive Development Program
Gilead is executing a deep, global clinical development strategy designed to expand Trodelvy’s utility across tumor types and earlier stages of cancer. Beyond ASCENT-07, the company is advancing:
- ASCENT-05: Phase 3 evaluation in high-risk early-stage triple-negative breast cancer (eTNBC)
- Additional Phase 3 studies in lung cancer and gynecologic malignancies
These trials reflect Gilead’s belief that Trop-2–directed ADCs may carry significant value in a wide range of solid tumors. Researchers hope that introducing such targeted strategies earlier in treatment pathways could potentially offer greater long-term benefit, particularly in cancers with historically poor prognoses.
Investigational Use Disclaimer
Trodelvy’s use as an initial treatment after endocrine therapy in HR+/HER2-negative metastatic breast cancer remains investigational. Its safety and efficacy for this specific population have not been established.
Similarly, its use in first-line metastatic TNBC—despite the positive Phase 3 findings—has not yet been approved by regulatory authorities.
HR+/HER2-Negative Metastatic Breast Cancer: An Overview
HR+/HER2-negative metastatic breast cancer is the most common subtype of breast cancer, representing approximately 70% of cases globally, or about 400,000 new diagnoses annually.
Treatment Pathways and Need for Better Options
Endocrine therapy is typically the first-line approach for HR+/HER2-negative mBC and has historically helped improve outcomes. Gilead Therapies such as aromatase inhibitors, estrogen receptor antagonists, and selective estrogen receptor degraders (SERDs) are often used either alone or in combination with CDK4/6 inhibitors.
However, nearly all patients with metastatic disease ultimately develop resistance to endocrine therapy. Once resistance occurs, chemotherapy becomes the primary treatment option, but response rates and survival outcomes are often limited. Toxicities associated with chemotherapy can significantly affect quality of life, and the attrition rate between successive lines of therapy is high.
These challenges highlight substantial unmet medical needs, especially for therapies that can extend survival while minimizing adverse effects.
Biomarker Considerations in HR+/HER2- Disease
ASCENT-07 evaluated Trodelvy across different HER2 expression levels:
- IHC 0
- IHC 1+
- IHC 2+/ISH−
These categories align with evolving understanding of HER2-low tumors, which have recently attracted attention because of new treatments targeting this subset. However, the progression of disease even after endocrine therapy continues to present a difficult clinical challenge regardless of HER2 expression, underscoring the need for additional therapeutic innovation.
Despite ASCENT-07 not meeting its primary endpoint, Gilead remains committed to advancing Trodelvy and other ADC programs. Continued follow-up for overall survival in ASCENT-07 will be crucial in determining whether the early positive trend strengthens into a meaningful survival benefit. Over time, these findings will help clinicians evaluate Trodelvy’s potential role in earlier-line settings for HR+/HER2-negative metastatic breast cancer.
Trodelvy’s broader clinical profile—including strong OS results in later-line disease and PFS improvement in first-line TNBC—reinforces its position as a Gilead foundational therapy among antibody-drug conjugates. The expanding global development program also signals optimism that ADCs may ultimately reshape treatment paradigms across multiple tumor types.
About the ASCENT-07 Study
The ASCENT-07 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of Trodelvy (sacituzumab govitecan-hziy) compared with treatment of physician’s choice chemotherapy in patients with locally advanced, inoperable, or HR+/HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) metastatic breast cancer who have received prior endocrine therapy and are candidates for cytotoxic chemotherapy. The study enrolled 654 patients across nearly 30 countries.
Patients were randomized 2:1 to receive either sacituzumab govitecan-hziy (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) or treatment of physician’s choice, which included a choice of single-agent chemotherapy including capecitabine, paclitaxel and nab-paclitaxel. Treatment continued until BICR-verified disease progression or unacceptable toxicity.
The primary endpoint of the study is PFS as assessed by BICR according to RECIST v1.1 criteria. Key secondary endpoints include overall survival, objective response rate, quality of life, and safety.
More information about ASCENT-07 is available at ClinicalTrials.gov: NCT05840211.
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