Pembrolizumab

iStock, Sundry Photography Combining Trodelvy with Keytruda and pushing it into the frontline setting could “potentially double” the ADC’s market in metastatic triple-negative breast cancer, according to analysts at Truist Securities. The combination of Gilead ’s anti-TROP2 antibody-drug conjugate Trodelvy and Merck’s PD-1 blocker Keytruda boosted progression-free survival as a frontline regimen in patients with a highly aggressive form of breast cancer, as per a Monday readout. Reacting to these findings, analysts at Truist Securities told investors in a Monday note that the late-stage “win” could “potentially double the addressable market” for Trodelvy in metastatic triple-negative breast cancer (mTNBC). Currently, Trodelvy is approved for mTNBC as a monotherapy, and only in patients who have undergone at least two prior lines of systemic therapies. Gilead did not reveal specific data in its Monday release, only announcing that Trodelvy plus Keytruda “significantly improved” progression-free survival (PFS) as opposed to Keytruda plus chemotherapy. The study, dubbed ASCENT-04/KEYNOTE-D19, involved patients with inoperable or mTNBC whose tumors express the PD-1 marker. More than 440 patients were enrolled in the study. Data for overall survival, a key secondary outcome, were not available in the readout, though Gilead noted an “early trend in improvement” in favor of the Trodelvy combo. Safety findings were consistent with what had previously been established for Trodelvy and Keytruda separately. ASCENT-04 did not document new signals of concern. Gilead plans to share Monday’s results with regulatory authorities and present detailed findings at an upcoming scientific meeting. Approval for this Trodelvy regimen in this indication is expected in 2026, according to the Truist analysts, who noted that if it wins regulatory clearance, it could “eventually face competition” from emerging PD-L1 combination therapies, particularly those that also use VEGF blockers. Of these, the Truist analysts specifically named Summit Therapeutics and its development partner Akeso, which in September 2024 shook the space with a Phase III readout from their HARMONi-2 study, claiming that their bispecific antibody ivonescimab beat Keytruda as a frontline therapy for non-small cell lung cancer (NSCLC). Ivonescimab works by targeting both the PD-1 and VEGF pathways, in turn disrupting cancer cells’ ability to evade the immune system and preventing the formation of new blood vessels that would otherwise enrich the tumor. Last year’s readout also showed that ivonescimab bested Keytruda in various patient subgroups, though analysts were measured in their optimism , highlighting the need for more robust overall survival findings and more diverse data. BioNTech is also playing in this space, announcing last month that its own PD-1/VEGF bispecific BNT327 led to a confirmed objective response rate of more than 85% in a Phase II NSCLC study.

– The First Pivotal Phase 3 Trial to Demonstrate Superiority of a TROP-2 Antibody-Drug Conjugate, Trodelvy, Plus Keytruda Versus Standard of Care Keytruda plus Chemotherapy in 1L mTNBC – – Trodelvy Plus Keytruda Shows an Early Trend in Improvement for Overall Survival Versus Standard of Care in Patients with Previously Untreated PD-L1+ (CPS ≥10) mTNBC – FOSTER CITY, CA, USA I April 21, 2025 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive topline results from the Phase 3 ASCENT-04/KEYNOTE-D19 study, demonstrating that Trodelvy ® (sacituzumab govitecan-hziy) plus Keytruda ® (pembrolizumab) significantly improved progression-free survival (PFS) compared to Keytruda and chemotherapy in patients with inoperable (unresectable) locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1 (CPS ≥ 10). The study met its primary endpoint, showing a statistically significant and clinically meaningful improvement in PFS. 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. “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,” said Dietmar Berger, MD, PhD, Chief Medical Officer, Gilead Sciences. “For patients with this difficult to treat type of breast cancer, these results potentially offer a new pathway that may redefine their treatment options.” “For patients with metastatic triple-negative breast cancer, there is a critical need for more effective treatment options,” said Dr. Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute and primary investigator of the ASCENT-04 study. “These data suggest that the combination of sacituzumab govitecan-hziy and pembrolizumab may offer a new treatment approach—bringing together a potent antibody drug conjugate with immunotherapy to improve outcomes for patients.” Overall survival (OS) is a key secondary endpoint and was not mature at the time of the PFS primary analysis. However, in the ASCENT-04 study, there was an early trend in improvement for OS with Trodelvy plus Keytruda. Gilead will continue to monitor OS outcomes, with ongoing patient follow-up and further analyses planned. Detailed results from the study will be presented at a future medical meeting and discussed with regulatory authorities. The use of Trodelvy plus Keytruda in patients with previously untreated PD-L1+ metastatic TNBC is investigational, and the safety and efficacy of this use have not been established. The significant and meaningful improvement in PFS demonstrated in ASCENT-04 further reinforces the potential of Trodelvy plus Keytruda as a much-needed new treatment option for patients with previously untreated inoperable (unresectable) PD-L1+ locally advanced or mTNBC. Trodelvy is the only approved Trop-2-directed antibody-drug conjugate (ADC) that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers: 2L+ mTNBC and pre-treated HR+/HER2- mBC. It is a Category 1 preferred treatment for both indications per the National Comprehensive Cancer Network ® (NCCN ® ) Clinical Practice Guidelines in Oncology (NCCN Guidelines i ) 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. With established healthcare professional experience, Trodelvy has shown consistent outcomes across clinical trials and real-world studies in 50,000+ patients across ~50 countries over ~5 years. It has now demonstrated improved outcomes in three Phase 3 breast cancer trials and is being studied in several ongoing clinical trials, aiming to extend survival across diverse tumor types and disease stages. Currently, Gilead has three ongoing Phase 3 studies investigating Trodelvy across HER2- (IHC 0, IHC 1+ or IHC 2+/ISH–) mBC, including the upcoming ASCENT-03 pivotal trial in 1L mTNBC patients who are not candidates for PD-L1 based therapy, the ASCENT-05 pivotal trial in patients with early-stage TNBC (eTNBC), and the ASCENT-07 pivotal trial in patients with HR+/HER2- mBC who have received endocrine therapy. Trodelvy is also being investigated in additional Phase 3 studies in other disease settings, including in lung and gynecological 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 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 being investigated for use in other TNBC and HR+/HER2- breast cancer populations, as well as a range of tumor types where Trop-2 is highly expressed, including extensive-stage small cell lung cancer and first-line metastatic non-small cell lung cancer where Trodelvy has shown clinical activity through the TROPiCS-03 proof-of-concept study and the EVOKE-02 proof-of-concept study, respectively. 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, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. i 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