An interview with: Javier C Cortés MD PhD, Breast Cancer Medical Oncologist, IOB Madrid, Institute of Oncology, Madrid, and International Breast Cancer Centre, Barcelona, Spain

BERLIN, Germany—Treatment with the antibody drug conjugate (ADC) sacituzumab govitecan (that targets the Trop-2 cancer-associated protein, delivering a cytotoxic topoisomerase inhibitor payload) has significantly improved progression-free survival in patients with newly-diagnosed metastatic triple-negative breast cancer who were not candidates for treatment with immune checkpoint inhibition and had received no prior therapy.

At the European Society for Medical Oncology (ESMO) 2025 Annual Congress Javier C Cortés MD PhD from the Institute of Oncology in Madrid and the International Breast Cancer Centre in Barcelona reported data from the ASCENT-03 study showing that treatment with sacituzumab govitecan brought clinically meaningful benefits with toxicities that were found to be manageable.

At the congress Cortés talked about the new findings with Peter Goodwin:

Audio Journal of Oncology: Javier C Cortes MD PhD

“[GOODWIN] Peter Goodwin here in Berlin …..……….Audio Journal of Oncology, I’m Peter Goodwin. 9:47secs

ESMO ABSTRACT:

LBA20 – “Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i)”

Speaker: Javier C. Cortés (Barcelona, Spain)

Authors: Javier C. Cortés (Barcelona, Spain), Aditya Bardia (Los Angeles, United States of America), Kevin Punie (Antwerp, Belgium), Carlos H. Barrios (Porto Alegre, Brazil), Sara A. Hurvitz (Seattle, United States of America, CA),Andreas Schneeweiss (Heidelberg, Germany), Joohyuk Sohn (Seoul, Republic of Korea), Eriko Tokunaga (Fukuoka, Japan), Adam M. Brufsky (Pittsburgh, United States of America, PA), Yeon Hee Park (Seoul, Republic of Korea), Binghe Xu (Beijing, China), Roberto Hegg (São Paulo, Brazil), Mafalda Oliveira (Barcelona, Spain), Alessandra Fabi (Rome, Italy), Natalya Vaksman (Miami, United States of America), Theresa Valdez (Miami, United States of America), Xinrui Zhang (Miami, United States of America), Catherine Lai (Foster City, United States of America, CA), Sara M. Tolaney (Boston, United States of America, MA)

Background

Significant PFS benefit was observed with SG vs chemo in pretreated metastatic (m)TNBC (ASCENT) and with SG + pembrolizumab vs chemo + pembrolizumab in first-line (1L) PD-L1+ mTNBC (ASCENT-04). For pts with mTNBC who cannot receive PD-(L)1i, treatment options are limited. We report primary results from the randomized phase 3 ASCENT-03 study (NCT05382299) of 1L SG vs chemo in pts with locally advanced unresectable or mTNBC who are unable to receive a PD-(L)1i.

Methods

Pts had centrally confirmed PD-L1− mTNBC (defined as combined positive score [CPS] < 10) or PD-L1+ mTNBC (CPS ≥ 10) but were unable to receive PD-(L)1i due to a comorbidity or prior use in the curative setting. Randomization (1:1) to SG (10 mg/kg IV, days 1 & 8 in 21-day cycles) or chemo (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) was stratified by disease status and geography. The primary end point was PFS by BICR. Key secondary end points included overall survival (OS), ORR and DOR by BICR, and safety.

Results

558 pts (279 in each group) with mTNBC were randomized. With a median follow-up of 13.2 mo, SG showed a significant improvement in median PFS vs chemo (9.7 vs 6.9 mo; HR, 0.62; 95% CI, 0.50-0.78; P < .0001); median DOR was 12.2 mo vs 7.2 mo (Table). OS data were immature. The most frequent grade ≥ 3 TEAEs were neutropenia (43%) and diarrhea (9%) with SG and neutropenia (41%) and anemia (16%) with chemo.

Conclusions

SG led to a statistically significant and clinically meaningful improvement in PFS and more durable responses vs chemo in 1L mTNBC. The safety profile of SG was manageable and consistent with its known profile; treatment discontinuation rate due to TEAEs was lower with SG vs chemo. These data support SG as a potential new standard of care for pts with previously untreated mTNBC who are unable to receive a PD-(L)1i. Table: LBA20

Clinical trial identification

NCT05382299.

Editorial acknowledgement

Editorial assistance was provided by Peggy Robinet, PharmD, PhD, and Sonal S. Joshi, PhD, of Parexel, and funded by Gilead Sciences, Inc.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

PRESS RELEASE:

ASCENT-03: Trodelvy® Demonstrates Highly Statistically Significant & Clinically Meaningful Improvement in Progression Free Survival in Patients With First-line Metastatic Triple-Negative Breast Cancer Who Are Not Candidates for Checkpoint Inhibitors

– Second Positive Phase 3 Trial in First-line Metastatic TNBC Where Trodelvy Has Demonstrated a Clinically Meaningful Benefit Versus Standard of Care Chemotherapy –

– Trodelvy Has the Potential to Be the Backbone of Treatment and the First Antibody-Drug Conjugate for All Patients Across First-line Metastatic TNBC –

FOSTER CITY, Calif.–(BUSINESS WIRE)– Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive topline results from the Phase 3 ASCENT-03 study of Trodelvy® (sacituzumab govitecan-hziy). The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy in patients with first-line metastatic triple-negative breast cancer (mTNBC) who are not candidates for PD-1/PD-L1 inhibitors, meaning they are PD-L1 negative or are ineligible to receive immunotherapy.

“Almost half of the patients diagnosed with metastatic triple-negative breast cancer do not receive treatment beyond first-line, demonstrating an urgent need for innovative treatment options in this early setting,” said Dr. Javier Cortes, Head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study. “Traditional chemotherapy has been the standard of care for early treatment of metastatic triple-negative breast cancer, and we know that therapeutic advances in this disease area serve a critical unmet need for patients and the broader oncology community.”

Together with the recently announced positive results from the ASCENT-04 study evaluating Trodelvy plus Keytruda® in patients with previously untreated PD-L1+ metastatic TNBC, Trodelvy now has the potential to be the backbone treatment for all patients across first-line mTNBC. Detailed data from the ASCENT-04 study will be shared during the American Society of Clinical Oncology (ASCO) meeting taking place May 30 – June 3, 2025.

“The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years versus chemotherapy,” said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. “By addressing this aggressive and difficult to treat disease earlier, we can potentially improve treatment options for the high unmet need that patients with metastatic triple-negative breast cancer face.”

The safety profile of Trodelvy in the ASCENT-03 study was consistent with prior studies, and no new safety signals were identified in this patient population. Overall survival (OS) is a key secondary endpoint and was not mature at the time of PFS primary analysis. No OS detriment was observed. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analysis planned.

Detailed results from the ASCENT-03 study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy in first-line mTNBC is investigational, and the safety and efficacy of this use have not been established.

Healthcare professionals have well-established experience with Trodelvy, which has shown generally consistent outcomes across both clinical trials and real-world studies in 60,000+ patients across 50+ countries over approximately five years. It is the only antibody-drug conjugate (ADC) with four positive Phase 3 trials in HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) metastatic breast cancer (mBC), and remains the only approved Trop-2-directed ADC that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers: 2L mTNBC and pre-treated HR+/HER2- mBC.

Trodelvy is a Category 1 preferred treatment for both currently approved indications per the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelinesi) and the only ADC with an ESMO Magnitude of Clinical Benefit Scale (MCBS) rating of 5 for mTNBC. Trodelvy also has an MCBS rating of 4 for women with HR+/HER2- mBC.

Currently, Gilead has additional ongoing Phase 3 studies investigating Trodelvy across HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer including the ASCENT-07 pivotal trial in patients with HR+/HER2- mBC who have received endocrine therapy, and the ASCENT-05 pivotal trial in patients with early-stage TNBC (eTNBC). Trodelvy is also being evaluated in additional Phase 3 studies across a range of tumor types, including in lung and gynecologic cancers.

Gilead would like to thank the patients, families, investigators and advocates who have contributed and continue to contribute to this important research. We remain committed to advancing care to address the unmet needs for the breast cancer community.

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Triple-Negative Breast Cancer (In Patients Who Are Not Candidates for PD-1/PD-L1 inhibitors)

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionately impacts younger, pre-menopausal as well as Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of mBC.

Chemotherapy remains the mainstay of treatment in first-line mTNBC patients who are not candidates for PD-1/PD-L1 inhibitors, and the need to improve outcomes continues to be high. In mTNBC overall, ~50% of patients do not receive treatment beyond 1L setting, demonstrating a need for additional effective earlier-line treatment options.

About the ASCENT-03 Study

The ASCENT-03 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of sacituzumab govitecan compared with treatment of physician’s choice in patients with previously untreated, locally advanced, inoperable, or metastatic triple-negative breast cancer (mTNBC) whose tumors do not express PD-L1, or who are PD-L1 positive and previously treated with a PD-(L)1 inhibitor in the curative setting. ~540 patients were enrolled across multiple study sites worldwide.

Patients were randomized 1:1 to receive either sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) or treatment of physician’s choice, which included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel. Treatment continued until blinded independent central review (BICR)-verified disease progression or unacceptable toxicity. Patients randomized to chemotherapy were eligible to crossover to sacituzumab govitecan upon disease progression.

The primary endpoint of the study is progression-free survival (PFS) as assessed by BICR according to RECIST v1.1. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), time to onset of response (TTR), patient-reported outcomes (PROs), and safety.

More information about ASCENT-03 is available at ClinicalTrials.gov: NCT05382299.

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 lung 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 tumor microenvironment through a bystander effect.

Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer.

Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression. These studies with Trodelvy, both in monotherapy and in combination with pembrolizumab, involve earlier lines of treatment for TNBC and HR+/HER2- breast cancer—including in curative settings—as well as in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.

INDICATIONS

TRODELVY® (sacituzumab govitecan-hziy) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate 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.