Merck’s Sacituzumab Tirumotecan Cuts Risk of Death by 32% in Advanced Endometrial Cancer in Phase 3 TroFuse-005 Trial
Merck, known as MSD outside the United States and Canada, has announced positive results from the pivotal Phase 3 TroFuse-005 clinical trial evaluating sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate (ADC), in patients with advanced or recurrent endometrial cancer. The study evaluated patients whose disease had progressed following previous platinum-based chemotherapy and anti-programmed death receptor 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) immunotherapy.
The findings demonstrated statistically significant and clinically meaningful improvements in both primary endpoints, overall survival (OS) and progression-free survival (PFS), as well as the key secondary endpoint of objective response rate (ORR), compared with treatment of physician’s choice (TPC), consisting of doxorubicin or paclitaxel.
According to Merck, TroFuse-005 is the first global Phase 3 trial in this patient population to demonstrate statistically significant improvements in both overall survival and progression-free survival with a TROP2-directed antibody-drug conjugate compared with chemotherapy. The results represent a potential advancement for patients with advanced or recurrent endometrial cancer who have limited treatment options after receiving platinum-based chemotherapy and immunotherapy.
The late-breaking results were presented for the first time during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2026 as Presentation #LBA11. The data were also selected for an official ESMO press briefing and published simultaneously in The Lancet.
The findings support the continued clinical development of sac-TMT as a potential treatment option for patients whose disease progresses after standard systemic therapies. Based on the TroFuse-005 results, the U.S. Food and Drug Administration (FDA) has accepted Merck’s Biologics License Application (BLA) for priority review, with a target action date of June 15, 2027.
TroFuse-005 Demonstrates Significant Overall Survival Improvement
TroFuse-005 evaluated sac-TMT in patients with advanced or recurrent endometrial cancer who had previously received platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 immunotherapy. The trial compared the investigational ADC with physician-selected chemotherapy, specifically doxorubicin or paclitaxel.
At the prespecified interim analysis, the study had a median follow-up of 14.0 months. The results showed that patients treated with sac-TMT experienced a substantial reduction in the risk of death compared with those receiving chemotherapy.
Sac-TMT reduced the risk of death by 32%, corresponding to a hazard ratio (HR) of 0.68, with a 95% confidence interval (CI) of 0.55–0.84 and a p-value of less than 0.0001. Median overall survival reached 19.0 months in the sac-TMT arm, compared with 12.1 months in the TPC arm.
This represented an improvement of 6.9 months in median overall survival, an important outcome for patients whose cancer has progressed following established chemotherapy and immunotherapy treatments.
The overall survival results are particularly relevant because patients with advanced or recurrent endometrial cancer who experience disease progression after these therapies may face a difficult treatment landscape. The improvement observed in TroFuse-005 suggests that sac-TMT could provide a new approach to extending survival in this population, subject to regulatory approval.
The results also distinguish sac-TMT from conventional chemotherapy in this clinical setting. Rather than demonstrating an improvement in only one measure of disease control, the investigational treatment met both of its primary endpoints, indicating benefits in overall survival and the time patients lived without disease progression or death.
Although the findings are encouraging, the results represent data from the reported interim analysis. Longer follow-up and additional clinical and regulatory assessments will contribute to a more complete understanding of the treatment’s long-term benefits and risks.
Progression-Free Survival Improves by 41%
In addition to extending overall survival, sac-TMT significantly improved progression-free survival, the second primary endpoint of the TroFuse-005 study.
Patients receiving sac-TMT experienced a 41% reduction in the risk of disease progression or death compared with those receiving physician’s-choice chemotherapy. The hazard ratio was 0.59, with a 95% CI of 0.50–0.70 and a p-value of less than 0.0001.
Median progression-free survival was 7.2 months for patients treated with sac-TMT, compared with 3.9 months for patients in the chemotherapy arm. This represented an improvement of 3.3 months.
Progression-free survival is an important measure in advanced cancer trials because it evaluates how long patients live without their disease worsening or death occurring. For patients whose cancer has returned or progressed after previous treatment, delaying further progression may help preserve treatment options and provide additional time before another therapeutic intervention becomes necessary.
The results showed that the benefit of sac-TMT extended beyond tumor response alone. The combination of improved progression-free survival and overall survival indicates that the treatment affected both disease control and the duration of patients’ lives in the study population.
The statistical significance of the two primary endpoints strengthens the evidence supporting sac-TMT’s potential role in treating advanced or recurrent endometrial cancer following platinum-based chemotherapy and immunotherapy.
Objective Response Rate More Than Doubles
TroFuse-005 also demonstrated a significant improvement in objective response rate, a key secondary endpoint measuring the proportion of patients whose tumors shrink by a predefined amount following treatment.
The objective response rate was 35.1% among patients receiving sac-TMT, compared with 17.3% in the chemotherapy arm. The absolute difference between the groups was 17.8 percentage points, with a 95% CI of 11.6–23.9 and a p-value of less than 0.00001.
The response rate observed with sac-TMT was more than twice that reported with physician’s-choice chemotherapy, providing additional evidence of its antitumor activity.
Complete responses were observed in 6.1% of patients in the sac-TMT arm and 4.5% of patients receiving chemotherapy. Complete response refers to the disappearance of detectable evidence of cancer according to the applicable response criteria, although it does not necessarily mean that the disease has been permanently eliminated.
The duration of response also favored sac-TMT. Patients receiving the investigational ADC had a median duration of response of 11.1 months, with a 95% CI of 9.2–13.0 months. In comparison, the median duration of response in the chemotherapy arm was 6.9 months, with a 95% CI of 5.4–9.1 months.
These findings suggest that sac-TMT not only helped a greater proportion of patients achieve a tumor response but also was associated with responses that lasted longer than those observed with chemotherapy.
Taken together, the improvements in objective response rate, duration of response, progression-free survival and overall survival provide a consistent picture of clinical activity across several important measures of treatment effectiveness.
Investigators Highlight Potential to Change Treatment Approaches
Domenica Lorusso, MD, the study’s global lead investigator, lead investigator for the European Network for Gynaecological Oncological Trial Groups (ENGOT), and professor of obstetrics and gynecology at Humanitas University and Humanitas San Pio X in Milan, highlighted the significance of the findings.
Lorusso noted that sac-TMT is the first TROP2-directed ADC to demonstrate an overall survival improvement compared with chemotherapy in this setting through a global Phase 3 clinical trial. She also emphasized the higher response rate and longer duration of response observed among patients treated with the investigational medicine.
According to Lorusso, endometrial cancer incidence and mortality rates are increasing worldwide, underscoring the need for additional effective treatments. She said the TroFuse-005 results have the potential to influence treatment approaches for patients who have already received platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 immunotherapy.
The findings address an important clinical need. Patients whose endometrial cancer progresses after these therapies may require subsequent treatment options that can provide meaningful disease control while balancing adverse effects and maintaining quality of life.
Dean Y. Li, MD, president of Merck Research Laboratories, also emphasized the overall survival benefit demonstrated in the trial.
Li said sac-TMT improved overall survival by almost seven months among women with endometrial cancer whose disease progressed following platinum-based chemotherapy and anti-PD-1 treatment. He described the result as a meaningful advance for patients who face a median survival of less than one year with currently available therapies in this setting.
Merck believes that sac-TMT’s bifunctional linker could contribute to its potential as a cornerstone treatment for certain patients with advanced or recurrent endometrial cancer. The company is working with regulatory authorities to advance the program and has indicated that it hopes to make the medicine available to patients as quickly as possible, subject to the FDA’s review and decision.
Safety Profile Remains Consistent With Earlier Studies
The safety findings from TroFuse-005 were consistent with previously reported studies of sac-TMT, and investigators identified no new safety signals.
Treatment-related adverse events (TRAEs) of any grade occurred in 97.1% of patients treated with sac-TMT, compared with 89.6% of patients receiving physician’s-choice chemotherapy.
Although treatment-related adverse events were common in both groups, Merck reported that most events in the sac-TMT arm were low grade and could be managed with supportive care and dose modifications. Treatment discontinuation rates remained relatively low in both groups.
Grade 3 or higher treatment-related adverse events occurred in 54.4% of patients receiving sac-TMT and 41.4% of patients in the chemotherapy arm. These higher-grade events highlight the importance of monitoring patients throughout treatment and managing adverse effects appropriately.
The most common Grade 3 or higher clinical safety events reported with sac-TMT were:
- Anemia: 23.7% of patients.
- Neutropenia: 20.1% of patients.
- Oral mucositis or stomatitis: 9.9% of patients.
Anemia involves reduced levels of red blood cells or hemoglobin and can contribute to fatigue and weakness. Neutropenia is characterized by a reduction in neutrophils, a type of white blood cell that helps the body fight infections. Oral mucositis or stomatitis refers to inflammation affecting the lining of the mouth and may cause discomfort, sores and difficulties with eating or drinking.
These adverse events can require clinical monitoring, supportive treatment, temporary treatment interruptions or dose adjustments, depending on their severity and the patient’s overall condition.
Despite the incidence of treatment-related adverse events, treatment discontinuation due to adverse events was reported in 3.1% of patients receiving sac-TMT, compared with 4.9% of patients receiving physician’s-choice chemotherapy.
Treatment-related adverse events leading to death occurred in 0.8% of patients in each treatment arm, corresponding to three patients per group.
The study also reported that health-related quality of life was maintained over time with sac-TMT. This finding is relevant in the context of advanced cancer treatment, where extending survival and delaying disease progression must be considered alongside treatment tolerability and patients’ day-to-day well-being.
The overall safety results provide additional context for evaluating sac-TMT’s clinical benefits. While higher-grade treatment-related adverse events were more frequent with the investigational ADC than with chemotherapy, the reported discontinuation rate was low. Further regulatory review will assess the full benefit-risk profile of the medicine.
FDA Accepts BLA for Priority Review
Following the TroFuse-005 results, the FDA accepted Merck’s Biologics License Application for priority review. The application seeks approval of sac-TMT for adults with endometrial cancer who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, either separately or in combination.
The FDA has established a Prescription Drug User Fee Act (PDUFA) target action date of June 15, 2027.
Priority review is intended to expedite the review of applications for medicines that, if approved, may offer significant improvements in the safety or effectiveness of treating, diagnosing or preventing serious conditions. The designation accelerates the review timeline but does not guarantee approval.
The FDA will evaluate the submitted evidence, including the efficacy results, safety findings and overall benefit-risk profile, before making a regulatory decision.
Merck also plans to discuss the TroFuse-005 data with regulatory authorities in other markets. These discussions could support the development of additional regulatory submissions, although approval timelines and requirements may differ between jurisdictions.
If approved, sac-TMT could become a new treatment option for patients with advanced or recurrent endometrial cancer following platinum-based chemotherapy and immunotherapy. The potential availability of an ADC with demonstrated improvements in overall and progression-free survival could be particularly important for patients who have limited options after disease progression.
Sac-TMT Advances Merck’s Broader Oncology Pipeline
The TroFuse-005 results form part of Merck’s broader clinical development strategy for sac-TMT, which is being developed in collaboration with Kelun-Biotech.
Merck’s TroFuse clinical development program currently includes 18 ongoing global Phase 3 trials evaluating sac-TMT across multiple tumor types and treatment settings. The company describes the program as the broadest Phase 3 development effort for a TROP2-directed ADC to date in terms of the range of diseases and treatment settings being investigated.
Ten of the Phase 3 trials focus on cancers affecting women, reflecting Merck’s continued investment in research addressing unmet needs in women’s health and oncology.
In addition to advanced or recurrent endometrial cancer, the program is evaluating sac-TMT in a range of malignancies, including bladder, breast, cervical, gastric, non-small cell lung and ovarian cancers.
The clinical program covers different stages of disease and is assessing sac-TMT both as a standalone treatment and in combination with immunotherapies. These studies are intended to determine where the investigational ADC may offer meaningful clinical benefits across different cancer types and treatment settings.
One of the ongoing studies is TroFuse-033, which is evaluating sac-TMT in first-line mismatch repair-proficient endometrial cancer. This trial addresses a different clinical setting from TroFuse-005, which focuses on patients whose advanced or recurrent disease has progressed after previous platinum-based chemotherapy and immunotherapy.
Merck reported that 14 of the 18 Phase 3 studies are designed to address unmet medical needs through potential first-in-class opportunities. The breadth of the program reflects the company’s strategy of evaluating sac-TMT across multiple indications rather than limiting its development to a single cancer type.
However, results from TroFuse-005 cannot automatically be applied to other malignancies or treatment settings. Each indication requires evaluation through its own clinical studies to establish the appropriate benefit-risk profile and determine whether regulatory approval is warranted.
A Potential New Option for Patients With Advanced Endometrial Cancer
Endometrial cancer develops in the lining of the uterus and is among the most common gynecologic cancers. Although treatment can be effective for many patients diagnosed at earlier stages, advanced, recurrent or treatment-resistant disease remains a significant challenge.
For patients whose cancer progresses after platinum-based chemotherapy and PD-1 or PD-L1 immunotherapy, subsequent treatment decisions can be difficult. Available options depend on individual clinical circumstances, previous treatments, tumor characteristics and the patient’s overall health.
The TroFuse-005 results suggest that sac-TMT may offer an additional approach for this population. The investigational ADC demonstrated improvements across overall survival, progression-free survival, objective response rate and duration of response compared with physician’s-choice chemotherapy.
The reported reduction in the risk of death by 32%, together with a 6.9-month improvement in median overall survival, represents the central finding of the study. The 41% reduction in the risk of disease progression or death and the more than twofold objective response rate further support the treatment’s potential.
At the same time, the safety results show that treatment-related adverse events remain an important consideration, particularly anemia, neutropenia and oral mucositis or stomatitis. Clinical monitoring and appropriate supportive care will be essential if the medicine receives approval.
With the BLA accepted for priority review and an FDA target action date of June 15, 2027, sac-TMT is progressing through the regulatory process in the United States. Merck’s planned engagement with other regulatory authorities may also help determine the medicine’s potential availability in additional markets.
The TroFuse-005 findings mark a significant development in the clinical investigation of TROP2-directed antibody-drug conjugates for advanced or recurrent endometrial cancer. The next steps will involve regulatory evaluation and continued research to clarify the treatment’s role in the broader oncology landscape.
If approved, sac-TMT could expand the treatment options available to patients whose disease has progressed after established therapies, while the ongoing TroFuse program will continue to assess its potential across several other tumor types and stages of cancer.
About TroFuse-005
TroFuse-005 is a randomized, active-controlled, open-label, multicenter, global Phase 3 trial (ClinicalTrials.gov,NCT06132958) evaluating sac-TMT versus TPC in patients with endometrial carcinoma who have received prior platinum-based chemotherapy and anti-PD-1/anti-PD-L1 immunotherapy either together or separately.
The trial enrolled 776 patients who were randomized to receive either sac-TMT or TPC, consisting of doxorubicin or paclitaxel. Sac-TMT (4 mg/kg) was administered on Day 1 of each two-week treatment cycle. Doxorubicin (60 mg/m²) was administered on Day 1 of each three-week treatment cycle and paclitaxel (80 mg/m²) was administered on Days 1, 8 and 15 of each four-week treatment cycle.
The study has dual primary endpoints: PFS by blinded independent central review (BICR), defined as the time from randomization to the first documented disease progression or death from any cause, and OS, defined as the time from randomization to death from any cause. A key secondary endpoint is ORR, and other secondary endpoints include duration of response, incidence of adverse events, treatment discontinuation due to adverse events and change from baseline in global health status/quality-of-life scores.
About sacituzumab tirumotecan (sac-TMT)
Sac-TMT is an investigational TROP2-directed ADC with a belotecan-derived topoisomerase I inhibitor payload and a unique bifunctional linker designed with the potential to maximize payload delivery to tumor cells and minimize payload loss while circulating in the body.
TROP2 is overexpressed on tumor cells compared to healthy cells in many common cancers, and through the TroFuse clinical development program, Merck is evaluating sac-TMT in 18 ongoing global Phase 3 trials across multiple tumor types, the broadest range of disease and treatment settings compared to any TROP2-directed ADC to date. The TroFuse development program spans early-to-late-stage disease in more than nine disease areas and includes more than 15,000 patients worldwide. Numerous Phase 3 trials are exploring sac-TMT as monotherapy and in combination with immunotherapies, aiming to improve survival and quality of life for patients with advanced and earlier-stage cancers.
About endometrial cancer
Endometrial cancer (also referred to as endometrial carcinoma) begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. More than 90% of uterine body cancers occur in the endometrium. In the U.S., it is estimated there will be approximately 68,270 patients diagnosed with endometrial cancer and approximately 14,450 patient deaths from the disease in 2026. Globally, endometrial cancer is the sixth most common cancer in women and the 15th most common cancer overall. Following primary treatment, patients face a risk of their cancer returning, often as distant metastasis, which is associated with poorer outcomes.
About Merck’s research in women’s cancers
Merck is advancing research aimed at expanding treatment options for certain breast and gynecologic (ovarian, cervical and endometrial) cancers, with a goal of improving outcomes for more patients affected by these diseases. Breast cancer and gynecologic cancers are the first and second most commonly occurring cancer types among women worldwide, respectively, and Merck aims to provide options to patients facing these devastating diseases.
With more than 30 clinical trials in more than 20,000 patients around the world, Merck is driving innovative research to purposefully advance standards of care in women’s cancers. Merck’s research efforts include trials focused on evaluating its medicines in earlier stages, as well as identifying novel mechanisms and new combinations with these treatments. Through our portfolio and pipeline, Merck is working to address the impact of women’s cancers on patients, their families and communities globally.
About the Merck and Kelun-Biotech strategic collaboration
Sac-TMT was developed by Kelun-Biotech. Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. Under a collaboration agreement, Kelun-Biotech has granted Merck the exclusive rights to develop, manufacture and commercialize sac-TMT in all territories outside of Greater China (which includes Mainland China, Hong Kong, Macau and Taiwan).
Merck’s focus on cancer
Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 20 novel mechanisms. With one of the largest clinical development programs across more than 25 tumor types, we strive to advance breakthrough science that will shape the future of oncology.
By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.