At the 2026 Society of Gynecologic Oncology (SGO) Annual Meeting in San Juan, Puerto Rico, the spotlight shone on a trio of promising antibody-drug conjugates (ADCs) that could reshape the landscape for women battling hard-to-treat gynecologic cancers. From new data on B7-H3–targeted therapies to the unveiling of GSK’s Mocertatug Rezetecan (Mo-Rez), the event showcased a flurry of advances that have researchers, clinicians, and patients alike paying close attention.
For decades, women facing recurrent or platinum-resistant ovarian, endometrial, or cervical cancer have had limited options—especially after standard chemotherapy fails. But the latest clinical trials unveiled at the SGO conference are offering a new sense of hope. According to CancerNetwork, the phase 1/2 trial of DB-1311/BNT324, a novel B7H3 ADC, showed notable antitumor activity in patients with previously treated cervical cancer and platinum-resistant ovarian cancer (PROC). The numbers speak volumes: among 33 patients with second- and third-line cervical cancer, the overall response rate (ORR) was 42.4%, with a disease control rate (DCR) of 81.8%. Median progression-free survival (PFS) clocked in at 7.0 months—a meaningful stretch for those who’ve already cycled through multiple lines of therapy.
Digging deeper, the DB-1311/BNT324 data revealed that the therapy’s impact held steady across tumor histologies. Patients with squamous cervical cancer (n=21) had an ORR of 42.9% and a DCR of 81.0%, while those with adenocarcinoma (n=11) saw a slightly higher ORR of 45.5% and a DCR of 81.8%. Notably, second-line patients experienced an ORR of 50.0% and a DCR of 91.7%, with a median PFS of 8.7 months. Even those in the third-line setting, typically a tough group to treat, showed an ORR of 40.0% and a DCR of 80.0%.
The story was similar—if not more impressive—in the PROC cohort. Out of 30 patients, the ORR soared to 53.3%, with a DCR of 83.3% and a median PFS of 9.5 months. For those who’d previously received bevacizumab, the ORR and DCR were 54.5% and 77.3%, respectively; prior PARP inhibitor use didn’t dampen efficacy either, with an ORR of 57.9% and a DCR of 84.2%. In a subset of patients with the longest follow-up (median 12.1 months), the ORR was 58.3% and the median duration of response reached 8.0 months. "[We saw] encouraging [overall response rate (ORR)] and [progression-free survival (PFS)] in patients with previously treated cervical cancer or PROC, regardless of prior treatment or histology," commented Dr. Ira S. Winer, who presented the findings.
Of course, efficacy is only half the equation. Safety data from the DB-1311/BNT324 trial were closely scrutinized. Treatment-related adverse events (TRAEs) occurred in 87.8% of patients, with grade 3 or higher events in 54.1%. Importantly, dose reductions and discontinuations due to TRAEs were relatively low, and no deaths were attributed to the treatment. The most common side effects were manageable, and the overall safety profile was deemed acceptable for this patient population. A global phase 2 trial combining DB-1311/BNT324 with pumitamig is now enrolling, aiming to build on these promising results.
Meanwhile, another B7-H3–targeting ADC, SYS6043, made waves with its early antitumor activity across a range of gynecologic cancers. As reported by OncLive, the phase 1/2 first-in-human study included heavily pretreated patients, many of whom had platinum-resistant or refractory disease and prior exposure to PARP inhibitors. Among 70 efficacy-evaluable ovarian cancer patients, SYS6043 achieved an ORR of 45.7% and a DCR of 88.6%, with a median PFS of 8.3 months. The benefit was even more pronounced in high-grade serous ovarian cancer, where the ORR hit 51.8%.
SYS6043 also showed promise in endometrial and cervical cancers. For 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. Cervical cancer patients saw an ORR of 35.9% and a DCR of 82.1%, with a median PFS of 5.8 months. "This is a multicenter, open-label phase 1/2 study to evaluate the safety, tolerability, and preliminary antitumor activity of SYS6043 monotherapy," explained Dr. Jing Zhou of the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences. Importantly, responses were observed regardless of B7-H3 expression status, though B7-H3–positive tumors trended toward better outcomes.
The safety profile of SYS6043 was in line with expectations for topoisomerase I–based ADCs. Among 142 safety-evaluable patients, grade 3 or higher TRAEs occurred in 38.0%. The most common side effects were anemia, decreased white blood cell and neutrophil counts, nausea, decreased appetite, and constipation—mostly low grade and manageable. Serious adverse events were reported in 26.8% of patients, but treatment-related discontinuation was rare (1.4%), and dose reductions occurred in 7.7%. Two cases of interstitial lung disease were noted, including one severe event that led to discontinuation. The 6 mg/kg every three weeks dosing schedule has been identified as the key dose moving forward.
Not to be outdone, GSK’s Mo-Rez (Mocertatug Rezetecan) ADC also captured headlines. As reported by The Guardian, early-stage trials involving 224 patients worldwide revealed that Mo-Rez shrank or eliminated tumors in 62% of ovarian cancer patients who had failed chemotherapy and in 67% of endometrial cancer patients. The therapy is administered intravenously every three weeks, and only a handful of patients needed to discontinue due to side effects, with nausea being the most common complaint.
These results, combined with data from a separate intermediate trial in China, have given GSK the confidence to leap directly into late-stage trials. Five global clinical studies are planned in the coming months, including sites in the UK. Hesham Abdullah, GSK’s global head of cancer research and development, summed up the sentiment at the SGO meeting: "Treatment of gynaecological cancers remains a major challenge, with a pressing need for new therapies that offer improved response rates. With Mo-Rez we now have compelling evidence of a promising clinical profile."
The stakes are high: endometrial cancer affects 1.6 million women globally, with 417,000 new cases each year, while ovarian cancer impacts 843,000 people and sees 240,000 new diagnoses annually. GSK, which only re-entered oncology less than a decade ago after selling its cancer portfolio to Novartis in 2015, now touts Mo-Rez as a "key asset" in its growing cancer pipeline. CEO Luke Miels, who took the helm in January 2026, has made it clear that speeding up drug development is a top priority. The company expects Mo-Rez to become a blockbuster, with peak annual sales projected to surpass £2 billion, helping GSK reach its ambitious £40 billion sales target by 2031.
In the competitive world of cancer therapeutics, these new ADCs—DB-1311/BNT324, SYS6043, and Mo-Rez—represent a beacon of hope for patients who have run out of options. While more research and larger trials are needed to confirm long-term benefits and safety, the strong response rates, manageable side effects, and rapid pace of development suggest that a new era in gynecologic cancer care may be just around the corner.
For patients and clinicians facing the daunting reality of recurrent or resistant disease, the pipeline has rarely looked more promising.