A Phase 3, Randomized, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Sacituzumab Tirumotecan Maintenance Treatment With or Without Bevacizumab Versus Standard of Care After Second-line Platinum-based Doublet Chemotherapy in Participants With Platinum-sensitive Recurrent Ovarian Cancer (TroFuse-022/ENGOT-ov84/GOG-3103)

Overview

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)

Mechanism of Action

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)

Efficacy

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:

• Endometrial Cancer Cohort (n = 44):
• Objective Response Rate (ORR): 34.1% (confirmed ORR: 27.3%)
• Disease Control Rate (DCR): 75.0%
• Median Progression-Free Survival (PFS): 5.7 months (95% CI, 3.7–9.4)

• Median Duration of Response (DOR): 5.7 months (range, 3.8 to 7.4+)

• Ovarian Cancer Cohort (n = 40):

• ORR: 40.0% (confirmed ORR: 35.0%)
• DCR: 75.0%
• Median PFS: 6.0 months (95% CI, 3.9–7.3)
• Median DOR: 5.3 months (range, 2.1 to 24.4+)

(onclive.com)

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:

• Sac-TMT Arm (n = 130):
• Median PFS: 5.7 months (95% CI, 4.3 to 7.2)
• ORR: 43.8%

• Median Overall Survival (OS): Not reached (95% CI, 11.2 to NE)

• Chemotherapy Arm (n = 133):

• Median PFS: 2.3 months (95% CI, 1.6 to 2.7)
• ORR: 12.8%
• Median OS: 9.4 months (95% CI, 8.5 to 11.7)

Sac-TMT demonstrated a statistically significant improvement in PFS and OS compared to chemotherapy. (ascopubs.org)

Safety

In the KL264-01 trial, treatment-related adverse events (TRAEs) occurred in all patients:

• Endometrial Cancer Cohort:
• Grade ≥3 TRAEs: 72.7%

• Common TRAEs: Anemia (88.6%), decreased white blood cell count (81.8%), decreased neutrophil count (65.9%)

• Ovarian Cancer Cohort:

• Grade ≥3 TRAEs: 67.5%
• Common TRAEs: Anemia (85.0%), decreased white blood cell count (60.0%), decreased neutrophil count (57.5%)

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:

• Neutrophil count decreased: 32.3%
• Anemia: 27.7%
• White blood cell count decreased: 25.4%

(ascopubs.org)

Further Reading

• Sacituzumab Tirumotecan Shows Antitumor Activity in Previously Treated Endometrial, Ovarian Cancers
• Sacituzumab Tirumotecan (SKB264/MK-2870) in Patients with Previously Treated Locally Recurrent or Metastatic Triple-Negative Breast Cancer: Results from the Phase III OptiTROP-Breast01 Study

Last updated: Apr 2025

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