ATI-1150

– First Pivotal Phase 3 Trial to Show Superiority of a TROP-2 Antibody-Drug Conjugate, Trodelvy, Plus Keytruda Versus Standard of Care in 1L Metastatic TNBC – – Early Trend in Improvement in Overall Survival Observed – FOSTER CITY, CA, USA I May 31, 2025 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced Trodelvy ® (sacituzumab govitecan-hziy) plus Keytruda ® (pembrolizumab) reduced the risk of disease progression or death by 35% (HR: 0.65) versus standard of care Keytruda plus chemotherapy in first-line treatment for patients with PD-L1+ (CPS ≥10) metastatic triple-negative breast cancer (TNBC). Trodelvy when given in combination with Keytruda resulted in a median progression-free survival (PFS) of 11.2 months vs 7.8 months when Keytruda was given in combination with chemotherapy. These data from the pivotal Phase 3 ASCENT-04/KEYNOTE-D19 study will be presented today as a late-breaking oral presentation at the 2025 ASCO Annual Congress (Abstract #LBA109). “These results are an important advancement for patients with PD-L1–positive metastatic triple-negative breast cancer, a population for whom first-line options remain limited,” said Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04 study. “By combining sacituzumab govitecan with pembrolizumab, we’re seeing meaningful gains in progression-free survival and a promising trend in overall survival—findings that could support a new frontline standard of care for this aggressive disease.” “The ASCENT-04 results build on Gilead’s aspiration of transforming the treatment of breast cancer with Trodelvy in earlier lines of therapy,” said Dietmar Berger, MD, PhD. “Together with the recently reported clinically meaningful topline results from our first-line monotherapy study, these data reinforce our confidence in Trodelvy’s utility both as a single agent and in combination with immunotherapy in the frontline metastatic TNBC setting. We are actively engaging with the FDA to explore a potential regulatory path forward for this combination for the benefit of patients.” For the primary endpoint, the median PFS was 11.2 months (95% CI: 9.3-16.7) with Trodelvy plus Keytruda compared to 7.8 months (95% CI: 7.3-9.3) with Keytruda plus chemotherapy, with a median follow-up of 14 months. A highly statistically significant and clinically meaningful improvement was observed with Trodelvy plus Keytruda (n=221), showing a 35% reduction in the risk of disease progression or death (HR: 0.65; p<0.001) in the intent to treat population compared to standard of care Keytruda plus chemotherapy combination (n=222). The PFS benefit was generally consistent across key prespecified subgroups. A numerically higher overall response rate was observed for the Trodelvy plus Keytruda combination [60% (95% CI: 52.9-66.3) versus 53% (95% CI: 46.4-59.9)], including 13% and 8% with a complete response, respectively, in the Trodelvy plus Keytruda and Keytruda plus chemotherapy arms. Notably, a substantially longer duration of response was observed with Trodelvy plus Keytruda [16.5 months (95% CI: 12.7-19.5) versus 9.2 months (95% CI: 7.6-11.3)]. Encouraging trends in overall survival (OS) were also observed, but data are immature at the time of PFS primary analysis. Overall survival follow-up remains ongoing and will continue to be monitored as a key secondary endpoint. The safety profile of Trodelvy plus Keytruda in the ASCENT-04 study was consistent with the known safety profile of each agent. No new safety signals were identified with the combination and the combination did not exacerbate the safety profile of either therapy. The most frequent (≥10% of patients) grade ≥3 treatment-emergent adverse events with Trodelvy plus Keytruda were neutropenia (43%) and diarrhea (10%), and with Keytruda plus chemotherapy were neutropenia (45%), anemia (16%) and thrombocytopenia (14%). Fewer patients discontinued treatment due to adverse events on the Trodelvy plus Keytruda arm than with Keytruda plus chemotherapy (12% vs. 31%). In addition to ASCENT-04, Gilead on May 23 announced topline results from ASCENT-03 demonstrating a highly statistically significant and clinically meaningful improvement in PFS compared to chemotherapy in patients with first-line metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitors . Detailed results from the ASCENT-03 study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy plus Keytruda in patients with first-line PD-L1+ metastatic TNBC and Trodelvy as monotherapy in patients with first-line metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitors are investigational, and the safety and efficacy of these uses have not been established. KEYTRUDA ® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About Triple-Negative Breast Cancer with PD-L1+ Tumors 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 is diagnosed more frequently in younger and premenopausal women and is more prevalent in 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 mTNBC, the five-year survival rate is 12%, compared with 28% for those with other types of mBC. Despite progress in treatment, first-line mTNBC has seen limited new approvals in recent years for tumors that express PD-L1+, and additional options are urgently needed. Despite recent advances, over 50% of patients do not receive treatment beyond first-line, reinforcing the urgent need for new options to help improve patient outcomes. Breast cancers expressing PD-L1 are overall more aggressive and associated with reduced survival time. About the ASCENT-04/KEYNOTE-D19 Study In 2021, Gilead entered a collaboration with Merck & Co. to investigate sacituzumab govitecan in combination with pembrolizumab in the Phase 3 trial, ASCENT-04/KEYNOTE-D19. The ASCENT-04/KEYNOTE-D19 study is a global, open-label, randomized Phase 3 trial evaluating the efficacy and safety of sacituzumab govitecan in combination with pembrolizumab compared with treatment of chemotherapy plus pembrolizumab in patients with previously untreated, inoperable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1. The study enrolled 443 patients across multiple study sites. Patients were randomized in a 1:1 ratio to receive either sacituzumab govitecan (10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle) plus pembrolizumab (200 mg intravenously on Day 1 of a 21-day cycle) or chemotherapy plus pembrolizumab. The chemotherapy regimen 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 allowed to crossover and receive sacituzumab govitecan upon disease progression. The primary endpoint of the study is progression-free survival (PFS) as determined by BICR using 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-04/KEYNOTE-D19 is available at ClinicalTrials.gov: NCT05382286 . 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: 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, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. SOURCE: Gilead Sciences