Sponsor: Merck Sharp & Dohme LLC (industry)
Phase: 3
Start date: Dec. 15, 2023
Planned enrollment: 614
Sacituzumab tirumotecan (sac-TMT), also known as SKB264 or MK-2870, is an investigational antibody-drug conjugate (ADC) targeting TROP2, a cell surface glycoprotein overexpressed in various cancers. (prnewswire.com)
Sac-TMT comprises a monoclonal antibody directed against TROP2 linked to a topoisomerase I inhibitor payload. This design facilitates targeted delivery of the cytotoxic agent to TROP2-expressing tumor cells, aiming to enhance antitumor efficacy while minimizing systemic toxicity. (prnewswire.com)
Endometrial and Ovarian Cancers
In the phase 2 KL264-01 trial (NCT04152499), sac-TMT monotherapy was evaluated in patients with previously treated advanced endometrial and ovarian cancers. Preliminary results presented at the 2024 ESMO Congress showed:
Median Duration of Response (DOR): 5.7 months (range, 3.8 to 7.4+)
Ovarian Cancer Cohort (n = 40):
Triple-Negative Breast Cancer (TNBC)
The phase 3 OptiTROP-Breast01 study (NCT05347134) compared sac-TMT to physician's choice of chemotherapy in patients with previously treated locally recurrent or metastatic TNBC. Results indicated:
Median Overall Survival (OS): Not reached (95% CI, 11.2 to NE)
Chemotherapy Arm (n = 133):
Sac-TMT demonstrated a statistically significant improvement in PFS and OS compared to chemotherapy. (ascopubs.org)
In the KL264-01 trial, treatment-related adverse events (TRAEs) occurred in all patients:
Common TRAEs: Anemia (88.6%), decreased white blood cell count (81.8%), decreased neutrophil count (65.9%)
Ovarian Cancer Cohort:
No TRAEs led to death, and there were no reports of drug-related interstitial lung disease or pneumonitis. (onclive.com)
In the OptiTROP-Breast01 study, common grade ≥3 TRAEs in the sac-TMT arm included:
Last updated: Apr 2025
The TroFuse-007 trial (NCT06170788) is a Phase 3 study evaluating the combination of sacituzumab tirumotecan (sac-TMT) and pembrolizumab versus pembrolizumab alone in the first-line treatment of metastatic non-small cell lung cancer (NSCLC) with PD-L1 tumor proportion score (TPS) ≥50%.
As of July 29, 2025, the trial is ongoing, with an expected completion date of January 25, 2028. (fdaaa.trialstracker.net)
Pembrolizumab monotherapy is a standard first-line treatment for advanced or metastatic NSCLC with PD-L1 TPS ≥50%. However, some patients do not respond or experience disease progression. TROP2 overexpression is associated with poor prognosis in NSCLC. Sac-TMT, a TROP2-targeting antibody-drug conjugate, has shown encouraging antitumor activity and a manageable safety profile in relapsed or refractory NSCLC. The complementary mechanisms of sac-TMT and pembrolizumab may provide enhanced antitumor activity when combined. (jto.org)
No early results from the TroFuse-007 trial have been reported as of August 3, 2025.
In December 2024, the FDA granted breakthrough therapy designation to sac-TMT for advanced or metastatic nonsquamous NSCLC with EGFR mutations after progression on TKI and platinum-based chemotherapy. This designation was based on phase 2 data highlighting sac-TMT's potential in NSCLC treatment. (pharmacytimes.com)
Last updated: Aug 2025
Goal: The trial aims to determine whether the combination of sacituzumab tirumotecan and pembrolizumab improves overall survival compared to pembrolizumab alone as first-line therapy in patients with metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression (TPS ≥50%).
Patients: The study population includes adults with histologically or cytologically confirmed metastatic squamous or nonsquamous NSCLC, without actionable EGFR, ALK, or ROS1 mutations, who have not received prior therapy for metastatic disease and have PD-L1 expression ≥50% as determined by central laboratory immunohistochemistry. Patients must have an ECOG performance status of 0–1, no active CNS metastases or severe ocular, GI, or autoimmune conditions, and adequate organ function.
Design: This is a randomized, open-label, phase 3 controlled trial comparing the investigational combination versus standard immunotherapy. Participants will be assigned to receive either sacituzumab tirumotecan plus pembrolizumab, or pembrolizumab alone, in the first-line setting.
Treatments: The experimental arm consists of sacituzumab tirumotecan given as an intravenous infusion on Days 1, 15, and 29 of each 6-week cycle plus pembrolizumab 400 mg IV every 6 weeks for up to 18 cycles. Sacituzumab tirumotecan is an antibody-drug conjugate targeting TROP2, highly expressed in several cancers. The payload is a belotecan-derivative topoisomerase I inhibitor released via a pH-sensitive and enzymatic cleavable linker, enabling a bystander effect. Early clinical data in NSCLC and breast cancer suggest substantial improvements in response rates and progression-free survival, with notable cytopenias as primary toxicities. The comparator arm is pembrolizumab monotherapy 400 mg IV every 6 weeks, a standard first-line option in this biomarker-selected NSCLC population.
Outcomes: The primary endpoint is overall survival. Key secondary endpoints include progression-free survival, objective response rate, duration of response, patient-reported quality of life measures (EORTC QLQ-C30 and QLQ-LC13), symptom control (dyspnea, cough, chest pain), time to deterioration in these domains, and standard safety endpoints including adverse event rates and treatment discontinuation due to toxicity.
Burden on patient: The patient burden is moderate. Treatment involves regular intravenous infusions every 3 weeks (for sacituzumab tirumotecan) and every 6 weeks (for pembrolizumab) for up to 18 cycles, as well as pretreatment medications to reduce infusion reactions during initial cycles of the combination therapy. Assessments are in line with typical registrational solid tumor trials, including imaging, laboratory monitoring, and health-related quality of life questionnaires. No protocol-mandated biopsies or intensive pharmacokinetic sampling are described. The frequency of clinic visits and infusions is higher in the combination arm compared to pembrolizumab monotherapy but remains broadly consistent with standard first-line NSCLC regimens.
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of squamous or nonsquamous NSCLC
* Confirmation that epidermal growth factor receptor- (EGFR-), anaplastic lymphoma kinase- (ALK-), or proto-oncogene tyrosine-protein kinase ROS (ROS1-) directed therapy is not indicated as primary therapy
* Provided tumor tissue that demonstrates programmed cell death ligand 1 (PD-L1) expression in ≥50% of tumor cells as assessed by an immunohistochemistry (IHC) central laboratory
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization.
* A life expectancy of at least 3 months.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
Exclusion Criteria:
* Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
* Has Grade ≥2 peripheral neuropathy.
* History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention.
* Received prior systemic anticancer therapy for their metastatic NSCLC.
* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor Note: Prior treatment with an anti-PD-1, anti-PD- L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic resectable NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
* Received radiation therapy to the lung that is \>30 Gy within 6 months of start of study intervention.
* Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
* Known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Known intolerance to sacituzumab tirumotecan or pembrolizumab and/or any of their excipients; for pembrolizumab, severe hypersensitivity (≥Grade 3) is exclusionary.
* Known hypersensitivity to sacituzumab tirumotecan or other biologic therapy.
* Active autoimmune disease that has required systemic treatment in the past 2 years.
* History of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
* Active infection requiring systemic therapy
* Concurrent active Hepatitis B and Hepatitis C virus infection.
* Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* History of allogeneic tissue/solid organ transplant.
* Requires treatment with a strong inhibitor or inducer of Cytochrome P450 3A4 (CYP3A4) at least 14 days before the first dose of study intervention and throughout the study.
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Ankara, 06800, Turkey
No email / 1-888-577-8839
Status: Recruiting
Denizli, 20070, Turkey
No email / 1-888-577-8839
Status: Recruiting
Istanbul, 34722, Turkey
No email / 1-888-577-8839
Status: Recruiting
Samsun, 55139, Turkey
No email / 1-888-577-8839
Status: Recruiting
Ankara, 06200, Turkey
No email / 1-888-577-8839
Status: Recruiting
Ankara, 06520, Turkey
No email / 1-888-577-8839
Status: Recruiting
Adana, 01140, Turkey
No email / 1-888-577-8839
Status: Recruiting
London, England, NW3 2QG, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Portsmouth, Hampshire, PO6 3LY, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Canterbury, Kent, CT1 3NG, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
London, London, City Of, SE1 9RT, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Central Middlesbrough, Middlesbrough, TS4 3BW, United Kingdom
No email / 1-888-577-8839
Status: Recruiting
Burbank, California, 91505, United States
No email / 888-577-8839
Status: Recruiting
Grand Junction, Colorado, 81501, United States
No email / 888-577-8839
Status: Recruiting
Marietta, Georgia, 30060, United States
No email / 888-577-8839
Status: Recruiting
Louisville, Kentucky, 40202, United States
No email / 888-577-8839
Status: Recruiting
Scarborough, Maine, 04074, United States
No email / 888-577-8839
Status: Recruiting
Worcester, Massachusetts, 01655, United States
No email / 508-334-3579
Status: Recruiting
Minneapolis, Minnesota, 55407, United States
No email / 888-577-8839
Status: Recruiting
Hattiesburg, Mississippi, 39401, United States
No email / 888-577-8839
Status: Recruiting
Reno, Nevada, 89502, United States
No email / 888-577-8839
Status: Recruiting
Cleveland, Ohio, 44106, United States
No email / 888-577-8839
Status: Recruiting
Corvallis, Oregon, 97330, United States
No email / 888-577-8839
Status: Recruiting
Houston, Texas, 77030, United States
No email / 888-577-8839
Status: Recruiting
Hanoi, Ha Noi, 100000, Vietnam
No email / +84904690818
Status: Recruiting
Hanoi, Ha Noi, 100000, Vietnam
No email / +842438326249
Status: Recruiting
Hanoi, Ha Noi, 100000, Vietnam
No email / +842471066858
Status: Recruiting
HCM, Ho Chi Minh, 700000, Vietnam
No email / +84 28 3869 0277
Status: Recruiting
Ho Chi Minh, 700000, Vietnam
No email / +842838554137
Status: Recruiting
Ho Chi Minh, 700000, Vietnam
No email / +842836227722
Status: Recruiting