Sponsor: Merck Sharp & Dohme LLC (industry)
Phase: 3
Start date: April 9, 2025
Planned enrollment: 770
Sacituzumab tirumotecan (sac-TMT; SKB264; MK-2870) is a TROP2-directed antibody–drug conjugate (ADC) that couples the same anti‑TROP2 monoclonal antibody used in sacituzumab govitecan to a belotecan‑derived topoisomerase I inhibitor payload (KL610023) via a sulfonyl‑pyrimidine–CL2A–carbonate linker; the average drug‑to‑antibody ratio (DAR) is ~7.4. Early- and late‑phase studies report antitumor activity across multiple solid tumors, most notably triple‑negative breast cancer (TNBC), hormone‑receptor–positive/HER2‑negative (HR+/HER2–) breast cancer, non–small cell lung cancer (NSCLC), and urothelial carcinoma. (jhoonline.biomedcentral.com)
Regulatory note: Sacituzumab tirumotecan received approval in China (November 2024) for pretreated advanced TNBC; it remains investigational in the United States with multiple ongoing phase 3 trials. (onclive.com)
Breast cancer
- Phase 1/2 (first‑in‑human, MK‑2870‑001; data cutoff June 29, 2023):
- TNBC expansion: ORR 34.8% at 4 mg/kg (n=23) and 38.9% at 5 mg/kg (n=36). (jhoonline.biomedcentral.com)
- HR+/HER2– expansion: ORR 31.7% (n=41); median DOR 9.5 months; median PFS 8.0 months; median OS 13.9 months. (jhoonline.biomedcentral.com)
- Phase 3 (OptiTROP‑Breast01; randomized vs physician’s‑choice chemotherapy; TNBC):
- PFS (BICR): 5.7 vs 2.3 months; HR 0.31 (95% CI 0.22–0.45).
- ORR: 43.8% vs 12.8%.
- Interim OS: HR 0.53 (95% CI 0.36–0.78). (ascopubs.org)
Lung cancer
- Phase 1b/2 (ASCO 2024; treatment‑naive metastatic NSCLC) sac‑TMT + KL‑A167 (anti‑PD‑1):
- Cohort 1A and 1B showed ORR 48.6% and 77.6%, respectively; 6‑month PFS rates 69.2% and 84.6%. A phase 3 study of sac‑TMT + pembrolizumab in first‑line PD‑L1 TPS ≥50% NSCLC is ongoing (NCT06170788). (ovid.com)
- Nature Medicine publications (April 2025) reported results in previously treated metastatic TNBC (phase 3) and advanced NSCLC (phase 1/2 and phase 2); DOIs: 10.1038/s41591‑025‑03630‑w (TNBC) and 10.1038/s41591‑025‑03638‑2 (NSCLC). (nature.com)
Urothelial carcinoma
- ASCO GU 2025 (MK‑2870‑001 cohort): sac‑TMT 5 mg/kg Q2W in previously treated unresectable/metastatic UC:
- Second‑line (n=11): ORR 45.5% (1 CR, 4 PR).
- Third‑line or later (n=38): ORR 26.3%.
- Median PFS ~5.0–5.8 months; median OS 11.5 months (3L+). (ascopubs.org)
Across studies, the most common treatment‑related grade ≥3 adverse events include myelosuppression (neutrophil count decreased, white blood cell count decreased) and anemia; dermatologic events and stomatitis occurred in early dose‑finding.
Notes: Dosing, efficacy, and safety data reflect study‑specific populations and cutoffs (e.g., June 29, 2023 for MK‑2870‑001 expansions; June 21/Nov 30, 2023 for interim PFS/OS in OptiTROP‑Breast01; June 30/May 21, 2024 for ASCO GU 2025 UC efficacy/safety). Cross‑trial comparisons should be made cautiously. (jhoonline.biomedcentral.com)
Last updated: Oct 2025
Goal: To determine whether maintenance sacituzumab tirumotecan, with or without bevacizumab, improves progression-free survival versus standard-of-care maintenance after completion of second-line platinum-based doublet chemotherapy in platinum-sensitive recurrent ovarian cancer, and to characterize safety and tolerability (Part 1 safety run-in; Part 2 efficacy).
Patients: Adults with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who are platinum-sensitive, have completed at least 4 cycles of first-line platinum doublet and 6 cycles of second-line carboplatin-based doublet, have ECOG 0–1, and can provide non-irradiated tumor tissue. Key exclusions include nonepithelial histologies, platinum-resistant or -refractory disease, significant ocular surface disease, inflammatory bowel disease, uncontrolled cardiovascular/cerebrovascular disease, prior steroid-requiring pneumonitis/ILD, active CNS metastases, more than two prior systemic lines, and recent anticancer therapy or radiotherapy. Controlled HIV, HBV, and HCV infection are permitted per protocol criteria.
Design: Multicenter, randomized, open-label Phase 3 study with a Part 1 safety run-in of sacituzumab tirumotecan plus bevacizumab, followed by Part 2 randomization to sacituzumab tirumotecan with optional bevacizumab versus standard-of-care maintenance with optional bevacizumab. Approximately 770 participants will be enrolled and followed for disease progression and survival.
Treatments: Experimental maintenance: sacituzumab tirumotecan 4 mg/kg IV every 2 weeks; bevacizumab 15 mg/kg IV every 3 weeks is mandated in Part 1 and optional in Part 2 at investigator discretion. Standard-of-care maintenance per local practice, with optional bevacizumab 15 mg/kg IV every 3 weeks. Sacituzumab tirumotecan is a TROP2-directed antibody-drug conjugate linking an anti-TROP2 antibody to a belotecan-derivative topoisomerase I inhibitor via a dual-cleavable linker (average drug-to-antibody ratio ~7.4). The membrane-permeable payload enables a bystander effect after extracellular pH-sensitive or intracellular enzymatic cleavage. In Phase 3 TNBC, sacituzumab tirumotecan improved PFS and OS versus chemotherapy and showed objective responses around 44%, with common grade ≥3 AEs including neutropenia, anemia, and leukopenia. Early-phase data in NSCLC suggest high response rates in combination with PD-L1 blockade; multiple Phase 3 programs are ongoing across tumor types.
Outcomes: Primary endpoints: Part 1 safety and tolerability (incidence of AEs and discontinuations within 6 weeks); Part 2 progression-free survival by blinded independent central review per RECIST 1.1. Key secondary endpoints: overall survival; incidence of AEs and treatment discontinuations; patient-reported outcomes including EORTC QLQ-C30 global health/quality of life, physical and role functioning, and EORTC QLQ-OV28 abdominal/GI symptom scale. Time horizon for efficacy and safety in Part 2 is up to approximately 4 years.
Burden on patient: Moderate. Treatment requires IV infusions every 2 weeks for sacituzumab tirumotecan with potential additional Q3W bevacizumab visits, leading to frequent clinic attendance. Standard safety labs and monitoring for ADC-related toxicities (myelosuppression, mucositis) and bevacizumab-related risks (hypertension, proteinuria, wound-healing, bleeding) are expected. Imaging at intervals typical for ovarian cancer maintenance and collection of a baseline tumor tissue sample add procedures but are standard for Phase 3 maintenance trials. No intensive pharmacokinetic schedules are specified; thus, while visit frequency is higher than oral maintenance strategies, overall procedural burden aligns with common infusion-based maintenance regimens.
Last updated: Oct 2025
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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No email / No phone
Status: Active, not recruiting