Sponsor: Merck Sharp & Dohme LLC (industry)
Phase: 3
Start date: April 9, 2025
Planned enrollment: 770
Sacituzumab tirumotecan (sac-TMT; SKB264; MK-2870) is an investigational antibody–drug conjugate (ADC) being evaluated across multiple solid tumors. The most mature evidence comes from randomized studies in previously treated metastatic triple-negative breast cancer (TNBC) and EGFR-mutated non-small-cell lung cancer (NSCLC). Earlier-phase activity has also been reported in hormone-receptor-positive breast, urothelial, endometrial, ovarian, cervical, gastric and other cancers. (nature.com)
Sac-TMT consists of a humanized antibody targeting TROP2, a cell-surface protein frequently overexpressed by epithelial cancers, conjugated through a hydrolytically cleavable linker to KL610023, a belotecan-derived topoisomerase I inhibitor. Its average drug-to-antibody ratio is approximately 7.4. After TROP2 binding and internalization, KL610023 is released and inhibits topoisomerase I, causing DNA damage and tumor-cell death. (frontiersin.org)
Toxicity is predominantly hematologic. In the TNBC phase 3 trial, hematologic toxicity was the most common treatment-related adverse-event category. In an earlier 59-patient TNBC cohort, 57.6% experienced grade 3 or worse treatment-related events, most commonly decreased neutrophils (25.4%), decreased white-cell counts (23.7%), anemia (22.0%) and decreased platelets (16.9%); no treatment-related deaths, interstitial lung disease or grade 3 or worse diarrhea were reported. (nature.com)
In the randomized EGFR-mutated NSCLC study, grade 3 or worse treatment-related adverse events occurred in 56% of sac-TMT recipients versus 72% with docetaxel. Longer follow-up and broader international experience remain important for defining uncommon or delayed toxicities. (pubmed.ncbi.nlm.nih.gov)
Last updated: Sep 2026
Goal: Evaluate the safety and tolerability of sacituzumab tirumotecan plus bevacizumab and determine whether maintenance sacituzumab tirumotecan, with or without bevacizumab, improves progression-free survival compared with standard care after second-line platinum-based chemotherapy.
Patients: Participants with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who have completed first-line platinum doublet chemotherapy and six cycles of second-line carboplatin doublet chemotherapy. ECOG performance status must be 0–1. Platinum-resistant or refractory disease and more than two prior systemic treatment lines are excluded.
Design: Multicenter, open-label study with an initial 6-week safety and tolerability part evaluating the combination, followed by a randomized comparison of sacituzumab tirumotecan–based maintenance versus local standard care. In the randomized part, bevacizumab may be added at the physician’s discretion in either group.
Treatments: Sacituzumab tirumotecan is given intravenously at 4 mg/kg every 2 weeks; bevacizumab, when used, is given intravenously at 15 mg/kg every 3 weeks. Sacituzumab tirumotecan is an investigational antibody–drug conjugate targeting TROP2 that delivers a topoisomerase I inhibitor to tumor cells, causing DNA damage. Randomized trials in previously treated triple-negative breast cancer and EGFR-mutated non-small-cell lung cancer have shown improved progression-free survival versus chemotherapy comparators; efficacy in this maintenance setting remains to be established. The comparator is local standard-of-care maintenance, with optional bevacizumab, an anti-VEGF therapy.
Outcomes: The initial part measures adverse events and treatment discontinuations due to adverse events over 6 weeks. The randomized part’s primary endpoint is blinded independent central review–assessed progression-free survival; secondary measures include overall survival, adverse events, treatment discontinuation, quality of life, physical and role functioning, and ovarian cancer–related abdominal and gastrointestinal symptoms, with follow-up of approximately 4 years.
Burden on patient: Estimated moderate burden. Intravenous treatment every 2 weeks, potentially alongside bevacizumab every 3 weeks, requires recurring clinic visits; imaging, safety assessments, questionnaires, and long-term follow-up add demands. Tumor tissue must be provided, but a new biopsy and intensive pharmacokinetic sampling are not specified.
Last updated: Sep 2026
Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.
Inclusion Criteria:
* Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
* Has received 4 or more cycles of platinum-based doublet chemotherapy in first-line and a total of 6 cycles of carboplatin-based doublet chemotherapy in second-line setting for ovarian cancer (OC).
* Has platinum-sensitive epithelial OC,
* Has provided tissue of a tumor lesion that was not previously irradiated
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
* Participants who are hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation (Part 1) or randomization (Part 2)
* Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
* Has an ECOG performance status of 0 to 1 assessed within 7 days before allocation (Part 1) or randomization (Part 2)
Exclusion Criteria:
* Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors), borderline tumors (low malignant potential), mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma
* Has platinum-resistant OC or platinum-refractory OC
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, or chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received more than 2 prior lines of systemic therapy for OC.
* Has received prior systemic anticancer therapy within 3 weeks or 5 half-lives (whichever is shorter) before allocation (Part 1) or randomization (Part 2)
* Has received prior radiotherapy within 2 weeks of allocation (Part 1) or randomization (Part 2), or has radiation related toxicities, requiring corticosteroids
* Has an additional malignancy that is progressing or has required active treatment within the past 3 years
* Has active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active infection requiring systemic therapy
CABA, C1118AAT, Argentina
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Prague, 150 06, Czechia
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Herlev, Capital Region, 2730, Denmark
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Nagoya, Aichi-ken, 464-8681, Japan
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Fairfax, Virginia, 22031, United States
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Jackson, Mississippi, 39216, United States
No email / No phone
Status: Active, not recruiting