Advances in Targeted Therapies and ADCs in Gynecologic Cancer Are Highly Anticipated at the 2025 ESMO Congress

As we head into October, the 2025 ESMO Congress is just around the corner, which will feature a plethora of exciting research and updates that could potentially be practice-informing for the gynecologic cancer landscape.

“We're excited about ESMO. [Something] we have to keep track of as we're hearing the new data is what trials are currently opening up [for enrollment],” Brian Slomovitz, MD, the director of Gynecologic Oncology and cochair of the Cancer Research Committee at Mount Sinai Medical Center in New York, said in an interview with OncLive®. “We have a whole slew of trials opening up in endometrial cancer, about 9 or 10 randomized phase 3 trials that were opening up through the GOG. These are all potentially practice-changing trials. We need to really keep an eye on where the data is going and what the new studies are that are coming out that'll help us do what's better for our patients.”

To preview specific abstracts, we spoke with the following experts in gynecologic cancers:

• Premal H. Thaker, MD, MS, the David G. and Lynn Mutch Distinguished Professor of Obstetrics and Gynecology and director of Gynecological Oncology Clinical Research, and interim chief of the Division of Gynecologic Oncology at Siteman Cancer Center in Saint Louis, Missouri
• Dana M. Chase, MD, a professor of Clinical Obstetrics and Gynecology in the Division of Gynecologic Oncology at the University of California, Los Angeles

Read more below to learn more about the highly anticipated presentations and what this research could mean for clinical practice.

What Phase 3 Trials Are of Interest at ESMO 2025?

LBA40 – WES-derived Aneuploidy score (W-AS) identifies MMRd patients with reduced benefit from immunotherapy in endometrial cancer. Multi-omic analysis of the phase III AtTEnd/ENGOT-EN7 trial

Session time: Sunday, 10/19, 10:15 - 10:20 CEST

Thaker: I'm really looking forward to the WES-derived aneuploidy score that is developed in [patients with] mismatch repair–deficient [dMMR] endometrial cancer with immunotherapy, because it's a multi-omic analysis of the [phase 3] AtTEnd/ENGOT-EN7 trial [NCT03603184].

As a physician, I feel like all patients who [have] dMMR disease should do well with immunotherapy, and sadly, we realize some patients do not. We can't figure that out with only tumor mutational burden scores or by PD-L1 scoring. I'm really interested to see what this new scoring system is, which might help us determine how to counsel patients better about [treatment] expectations. Right now, it's very binary: [patients are either] mismatch repair proficient or deficient, and that's how we've looked at it before. I'm very excited to see what that late-breaking abstract will lend us to be more clinically relevant for our patients.

LBA44 – Durvalumab + paclitaxel/carboplatin + bevacizumab followed by durvalumab, bevacizumab + olaparib maintenance in patients with newly diagnosed non-tBRCA-mutated advanced ovarian cancer: final overall survival from DUO-O/ENGOT-ov46/GOG-3025

Session time: Sunday, 10/19, 10:51 – 10:56 CEST

Thaker: I'm interested in finally looking at the overall survival [OS] benefit from [the phase 3] DUO-O trial [NCT03737643].1 A lot of us haven't adopted using the addition of durvalumab [Imfinzi] with bevacizumab [Avastin] and olaparib [Lynparza] with our standard-of-care chemotherapy. When they've looked at the OS, are there some groups [of patients who] may benefit even more? Carol Aghajanian, MD, of Memorial Sloan Kettering Cancer Center, is going to be presenting [this late-breaking abstract (LBA)], so I'm hopeful that it could help us, once again, realize which patients benefit from multi-drug therapy, because that's a lot of maintenance therapy to offer a patient. However, I'm sure there are some subgroups where hopefully we can [better] understand. I'm enthusiastic to see that because all of us are still hopeful for immunotherapy to work in ovarian cancer—this could be something we can find and tease out.

LBA45 – ROSELLA (GOG3073, ENGOTov72, APGOT-OV10): relacorilant + nab-paclitaxel in the subgroup of patients with platinum-resistant ovarian cancer (PROC) previously exposed to a PARP inhibitor

Session time: Sunday, 10/19, 10:56 – 11:01 CEST

Thaker: One that's really exciting to me is looking at the subgroup analysis of the phase 3 ROSELLA trial [NCT05257408] in patients who had prior exposure to PARP inhibitors because we always feel that patients who have had prior PARP exposure, depending on how long they've been on that maintenance therapy, may have different progression-free survival benefits. Are we seeing that with this very novel, different agent, or is that not an issue at all with the use of relacorilant? I'm interested to see [the results], even though I know this is a subgroup analysis. It's just an important one because it also may help us realize what subgroups might benefit more from this novel therapy. It was a breakthrough for us at the 2025 ASCO Annual Meeting, looking at the FDA information that we saw.2

What Antibody-Drug Conjugate (ADC)–Related Data Look Interesting at ESMO 2025?

LBA42 – Raludotatug deruxtecan (R-DXd) in patients (pts) with platinum-resistant ovarian cancer (PROC): primary analysis of the phase 2 dose-optimization part of REJOICE-Ovarian01

Session time: Sunday, 10/19, 15:45 – 15:55 CEST

Chase: [R-DXd] is an ADC that targets CDH6, and it has a topoisomerase I payload. Nevertheless, I would be interested to see what the dose looks like for this ADC and the safety profile. The initial efficacy would also be interesting to see. It’s an ADC world right now, meaning a lot of the abstracts we see presented include ADCs in varying [patients with] gynecologic cancer, and they have pretty similar efficacy, but different safety profiles, with different or varying expressions of the target, in the patient's cancer cells.

1065MO – First-in-human study of AZD5335, a folate receptor α (FRα)-targeted antibody-drug conjugate, in patients with platinum-resistant ovarian cancer

Session time: Sunday, 10/19, 10:33 – 10:38 CEST

Chase: This is a new ADC with a topoisomerase I payload. Most of our ADCs that are in clinical trial right now have a topoisomerase I payload; however, what's interesting about this drug is that maybe it has a different toxicity profile than our current ADCs that target FRα, meaning, does it have ocular toxicity? Maybe not. Does it have peripheral neuropathy in patients? Maybe not. Therefore, it's going to be interesting to see its toxicity profile. Patients who are using this therapy get interstitial lung disease, so I'd be interested to see its efficacy, its safety profile, and then potentially whether it's effective in patients with varying FRα expression.

LBA43 – NAPISTAR 1-01: a phase 1 dose escalation study of TUB-040, a novel NaPi2b-targeting exatecan antibody-drug conjugate (ADC) in patients with platinum-resistant ovarian (PROC) high grade serous carcinoma (HGSC)

Session time: Sunday, 10/19, 10:38 – 10:43 CEST

Thaker: This LBA is interesting because a NaPi2b ADC is being resurrected in platinum-resistant ovarian cancer. It'd be nice to see this phase 1 study, because we know that NaPi2b is a very viable target, although we had issues with a prior ADC. Perhaps this ADC will [open up] an avenue to really target that pathway in platinum-resistant ovarian cancer. I'm excited to see that data as well; just because 1 drug doesn't necessarily work as well as we think doesn't mean that the biology of that pathway is not relevant.

What Targeted Therapy–Related Sessions Have Caught Your Eye?

1512O – NI-1801, a mesothelin x CD47 bispecific antibody: safety and activity as single agent and in combination with pembrolizumab, in heavily pretreated (≥ 4 prior lines) mesothelin expressing platinum resistant epithelial ovarian cancer patients

Session time: Monday, 10/20, 10:45 – 10:55 CEST

Chase: [NI-1801 is] a bispecific antibody that binds mesothelin and CD47 together on tumor cells to prevent CD47 from interacting with a receptor on immune cells that [have] macrophages or other immune cells. This includes [patients with] heavily pretreated, mesothelin-expressing, platinum-resistant ovarian cancer and epithelial ovarian cancer, [which includes] patients who have 4 or more prior lines [of therapy].

The reason this interests me is 2-fold: first, for these patients who have been heavily pre-treated, we're seeing them more clinically, and we're having fewer options for them. Typically, clinical trials include patients who have 3 or fewer prior lines of therapy. Therefore, to have 4 or more prior lines and have patients on a clinical trial is interesting to me, because we have those patients in the clinic, and we don't have many available therapies for them.

Additionally, many patients have seen ADCs at this point, especially with a topoisomerase 1 payload, and so it excludes them from ADC trials that have a topoisomerase 1 payload. Therefore, this is an immunotherapy-type agent that potentially wouldn't exclude the patient if they had had a prior ADC with a topoisomerase 1 payload. Second to that, we are still trying to figure out if immunotherapy can be active in [patients with] ovarian cancer. From my review of the literature, this has not yet been studied in ovarian cancer—this bispecific antibody with this mechanism of action. I would be interested to see if this has a response rate or a profile that could be interesting in [patients with] ovarian cancer.

This is just an introduction to this trial. It should be interesting to see if there's activity and how safe it is. Of course, it would have to be rolled out into phase 2 and phase 3 trials. Nonetheless, this is a particularly important patient population because there's really an unmet need in this group of patients with heavily pretreated, platinum-resistant ovarian cancer.

LBA38 – Phase 3 study of camrelizumab plus famitinib versus platinum-based chemotherapy as first-line therapy for recurrent or metastatic cervical cancer

Session time: Sunday, 10/19, 14:45 – 14:55 CEST

Chase: We don't have a lot of new phase 3 data that is being presented [in the gynecologic space]…[However,] we're getting some secondary analysis of other phase 3 trials. From what I can tell, there’s only 1 new phase 3 clinical trial that's being presented at ESMO 2025. It’s a phase 3 study of an anti-PD1 inhibitor called camrelizumab plus famitinib, which is a multitargeted TKI, and this anti-PD1 inhibitor is actually approved in China. It's not approved in the United States; however, this is a trial comparing the combination with platinum-based chemotherapy as first-line therapy for recurrent or metastatic cervical cancer.

I would be interested to see how that combination compares to platinum-based chemotherapy in recurrent or metastatic cervical cancer. Of course, it'd be nice to have a nonchemotherapy option for these patients, because chemotherapy causes so much toxicity. This is a phase 3 trial, which was really the gold standard of clinical trial research in terms of drug efficacy and toxicity. It’s interesting that we only have one phase 3 trial that's presented, and that's the one; however, there are some novel treatments that look like they're new to being presented that could maybe be developed further in some of these gynecologic cancers.

References

1. Durvalumab treatment in combination with chemotherapy and bevacizumab maintenance durvalumab, bevacizumab and olaparib treatment in advanced ovarian cancer patients (DUO-O). ClinicalTrials.gov. Updated January 29, 2025. Accessed September 30, 2025. https://clinicaltrials.gov/study/NCT03737643
2. Olawaiye A, Gladieff L, Gilbert L, et al. ROSELLA: a phase 3 study of relacorilant in combination with nab-paclitaxel versus nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer (GOG-3073, ENGOT-ov72). J Clin Oncol. 2025;43(suppl 17). doi:10.1200/JCO.2025.43.17_suppl.LBA5507