The B7-H3–targeting antibody-drug conjugate SYS6043 demonstrated early antitumor activity with a manageable safety profile in heavily pretreated patients with ovarian, endometrial, or cervical cancer, according to results from a phase 1/2 first-in-human study (NCT07415863) presented during the 2026 SGO Annual Meeting.1
Among 70 efficacy-evaluable patients with ovarian cancer, SYS6043 achieved an objective response rate (ORR) of 45.7% and a disease control rate (DCR) of 88.6%. Responses were observed regardless of B7-H3 expression status, although numerically higher activity was seen in B7-H3–positive tumors (ORR 48.2% vs 36.4%). In patients with high-grade serous ovarian cancer, the ORR reached 51.8%. The median duration of response was 6.9 months, and the median progression-free survival (PFS) was 8.3 months.
SYS6043 also demonstrated activity in other gynecologic tumor types. In endometrial cancer, the ORR was 33.3% overall and 41.7% in the 6 mg/kg cohort, with a median PFS of 8.0 months. In cervical cancer, SYS6043 achieved an ORR of 35.9% and a DCR of 82.1%, with a median PFS of 5.8 months overall and 5.7 months in the 6 mg/kg cohort.
“This is a multicenter, open-label phase 1/2 study to evaluate the safety, tolerability, and preliminary antitumor activity of SYS6043 monotherapy,” Jing Zhou, MD, of the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences, explained in his presentation of the data.
SYS6043 Demonstrates Early Activity Across Gynecologic Cancers
- Among patients with pretreated ovarian cancer, SYS6043 achieved an objective response rate of 45.7% and median PFS of 8.3 months, including higher activity in high-grade serous disease.
- Clinical activity was also observed in endometrial and cervical cancers, with objective response rates of 33.3% and 35.9%, respectively, supporting broad antitumor potential across gynecologic malignancies.
- The safety profile was manageable and consistent with topoisomerase I–based antibody-drug conjugates, with grade 3 or higher treatment-related adverse effects reported in 38.0% of patients and 6 mg/kg every 3 weeks identified as a key dose for further development.
What was the rationale for, and design of, this phase 1/2 study?
B7-H3 is highly expressed across a range of solid tumors and has been associated with poor prognosis, including increased recurrence and reduced survival in gynecologic cancers. SYS6043 is an investigational antibody-drug conjugate composed of a B7-H3–directed antibody linked via a cleavable linker to a topoisomerase I inhibitor payload, with a drug-to-antibody ratio of approximately 6.
This ongoing, multicenter, open-label phase 1/2 study is evaluating the safety, tolerability, and preliminary antitumor activity of SYS6043 monotherapy, with dose-escalation and expansion cohorts designed to establish the recommended dose.
The enrolled population reflected a heavily pretreated cohort, particularly in ovarian cancer, where most patients had platinum-resistant or refractory disease, more than 60% had received prior PARP inhibitors, and a majority had received 3 or more prior lines of therapy. Moreover, B7-H3 expression was observed in 78.1% of ovarian tumors, 59.6% of cervical tumors, and 81.8% of endometrial tumors, supporting its role as a therapeutic target.
Dose-limiting toxicities were observed at 10 mg/kg every 3 weeks, and the maximum tolerated dose for this schedule was established at 8 mg/kg, with 6 mg/kg every 3 weeks emerging as a key dose for further evaluation.
What was the safety profile of SYS6043?
Among 142 patients evaluable for safety, grade 3 or higher treatment-related adverse events occurred in 38.0% of patients.
The most common toxicities were hematologic and gastrointestinal, including anemia, decreased white blood cell and neutrophil counts, nausea, decreased appetite, and constipation. These events were primarily low grade and manageable.
Serious adverse effects occurred in 26.8% of patients, with treatment-related discontinuation in 1.4% and dose reductions in 7.7%. Two cases of interstitial lung disease were reported, including one grade 4 event leading to discontinuation.
Overall, the safety profile was consistent with other topoisomerase I–based antibody-drug conjugates and did not reveal unexpected safety signals. SYS6043 continues to be evaluated in ongoing study cohorts, with 6 mg/kg every 3 weeks identified as a key dose for further clinical development.
Editor’s Note: Zhou reported no relevant disclosures.
References
Zhou J, et al. SYS6043, a B7-H3 targeting antibody-drug conjugate in patients with advanced gynecologic cancers: a phase 1/2, first-in-human study. Presented at: 2026 Society of Gynecologic Oncology Annual Meeting; April 10-13, 2026; San Juan, Puerto Rico.
