Gilead’s Trodelvy Meets Primary Endpoint of Progression-Free Survival in Phase III ASCENT-03 Breast Cancer Study

Key takeaways

Trodelvy achieves primary endpoint in first-line mTNBC: The ASCENT-03 Phase III trial demonstrated a statistically significant and clinically meaningful improvement in PFS for Trodelvy versus physician’s choice of chemotherapy in first-line metastatic triple-negative breast cancer—a key development for future protocol design and trial strategy in this population.

Study design reflects real-world treatment scenarios: The open-label, randomized design with physician’s choice comparator arms (gemcitabine + carboplatin, paclitaxel, nab-paclitaxel) reflects practical flexibility in clinical settings, enhancing applicability of trial results and easing operational execution.

Safety profile consistency supports operational scalability: The consistency of Trodelvy’s safety profile across studies, including ASCENT-03, simplifies site training, monitoring plans, and patient management protocols—reducing operational complexity for future trials involving this agent.

Gilead has shared positive results from the Phase III ASCENT-03 clinical trial of Trodelvy (sacituzumab govitecan-hziy). In patients with first-line metastatic triple-negative breast cancer (mTNBC) who are not candidates for PD-1/PD-L1 inhibitors, the study showed that Trodelvy achieved a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy, meeting the primary endpoint.¹

In a press release, Javier Cortes, MD, PhD, head of the International Breast Cancer Center in Spain and principal investigator of the ASCENT-03 study, said: “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. 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.”

ASCENT-03 trial design and treatment comparison

ASCENT-03 (NCT05382299) is a global, open-label, randomized trial. Its primary objective was to compare PFS between Trodelvy and the treatment of physician's choice in mTNBC patients. The study randomized 540 participants 1:1 to receive Trodelvy at 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle, or the treatment of physician’s choice, which included gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel.²

Key secondary endpoints include OS, ORR, and patient-reported outcomes

In addition to the primary endpoint of PFS, the study included key secondary endpoints of overall survival (OS), objective response rate (ORR), duration of response (DoR), time to onset of response, patient-reported outcomes, and safety.

In the press release, Dietmar Berger, MD, PhD, chief medical officer, Gilead Sciences, added: “The ASCENT-03 outcome represents the first clinically meaningful advance for this patient population in over 20 years versus chemotherapy. 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 ASCENT-03 remained consistent with previous clinical data, with no new safety signals discovered. While OS data were immature at the time of the primary analysis, no detriment was observed. Gilead will continue to monitor this endpoint with ongoing patient follow-up.

In light of these positive results, Gilead plans on sharing full data from ASCENT-03 at an upcoming medical conference. The company also announced it will be sharing detailed data from the Phase III ASCENT-04/KEYNOTE-D19 study at the upcoming American Society of Clinical Oncology (ASCO) meeting.

ASCENT-04 underscores potential of Trodelvy plus Keytruda in PD-L1+ mTNBC

Gilead shared initial data from ASCENT-04/KEYNOTE-D19 earlier in April. Alongside Merck’s Keytruda (pembrolizumab), Trodelvy significantly improved PFS compared to Keytruda plus chemotherapy in patients with previously untreated, PD-L1-positive mTNBC.³

The ASCENT-04/KEYNOTE-D19 trial (NCT05382286) enrolled 443 patients across multiple sites globally. The primary endpoint was PFS with key secondary endpoints including OS, ORR, and DoR.

In a press release from the time, Berger said: “These findings are the first to show the transformative potential of an antibody-drug conjugate combined with an immuno-oncology agent in early treatment lines of metastatic breast cancer. For patients with this difficult to treat type of breast cancer, these results potentially offer a new pathway that may redefine their treatment options.”

Trodelvy is currently approved in over 50 countries for second-line or later treatment of mTNBC, and in over 40 countries for pre-treated HR+/HER2- metastatic breast cancer (MBC). In addition to ASCENT-03 and ASCENT-04/KEYNOTE-D19, the therapy is being evaluated in other trials targeting HER2-negative MBC subtypes including ASCENT-05 in early-stage TNBC, and ASCENT-07 in HR+/HER2- MBC patients post-endocrine therapy.

References

2. Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer (ASCENT-03). ClinicalTrials.gov. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT05382299?term=%20NCT05382299&rank=1