No woman left behind – Ovarian cancer enters new eras of development
Today marks World Ovarian Cancer Day, a global effort to recognize the women living with this disease and the accelerating progress being made to treat it. This year’s theme, “No Woman Left Behind,” captures a central inequity in ovarian cancer: scientific advances are expanding treatment options, yet many women globally still face barriers to timely diagnosis, specialist care, biomarker testing, and novel therapies. In 2022, an estimated 324,603 women were diagnosed with ovarian cancer worldwide and 206,956 died of the disease. The World Ovarian Cancer Coalition (WOCC) reports that around 70% of women diagnosed live in low- and middle-income countries, and that by 2050, diagnoses are projected to rise by 55%, with deaths rising by close to 70%.
Much of that increase will occur in regions where novel therapies remain unapproved or inconsistently available. At the same time, the ovarian cancer treatment landscape is rapidly evolving beyond platinum-taxane chemotherapy toward biomarker-targeted treatments, for which biomarker testing is required.
In the 1L maintenance setting, PARP inhibitors marked one of the first major shifts toward biomarker-directed ovarian cancer treatment, beginning with the FDA approval of olaparib (Lynparza, AstraZeneca) in December 2018 for BRCA-mutated disease following response to 1L platinum-based chemotherapy, followed by niraparib (Zejula, GSK). More recently, innovation has extended into platinum-resistant disease, although many new options remain limited to molecularly defined subgroups. AbbVie’s mirvetuximab soravtansine (Elahere), the first antibody-drug conjugate (ADC) approved specifically for ovarian cancer, gained FDA full approval in March 2024 for patients with high FRα-expressing tumours, reinforcing both the promise and the access challenge of biomarker-restricted treatment. Similarly, in the last quarter, pembrolizumab (Keytruda, Merck) plus paclitaxel ± bevacizumab was approved for another restricted population: patients with platinum-resistant disease whose tumours express PD-L1 (CPS ≥1).
Last quarter also marked the FDA approval of relacorilant (Lifyorli, Corcept) in combination with nab-paclitaxel, representing a different kind of advance. As the first approved selective glucocorticoid receptor antagonist in ovarian cancer, relacorilant introduces a novel mechanism designed to modulate glucocorticoid receptor signaling and enhance chemotherapy activity, rather than target a tumour-associated antigen or immune biomarker. Thus, unlike FRα- or PD-L1-directed strategies, relacorilant does not require biomarker selection, positioning it as an option for a wide range of patients with platinum-resistant ovarian cancer.
Similarly, ADC development is now casting a wider net across ovarian cancer, with late-stage programs evaluating whether targeted payload delivery can move beyond biomarker-restrictions, show activity regardless of receptor expression, and move beyond the poor-prognostic platinum-resistant setting. Select examples of the wide-range of programs include:
- RAINFOL: Genmab’s FRα-directed ADC rinatabart sesutecan (Rina-S) is the next ADC expected to be approved in ovarian cancer, with a first launch guided to 2027 in platinum-resistant patients, regardless of FRα expression levels. Notably, Genmab recently initiated a head-to-head trial of Rina-S against the standard-of-care platinum-doublet chemotherapy typically used in 2L platinum sensitive patients
- BEHOLD: Originating in China from Hansoh Pharma, GSK’s B7-H4-directed ADC mocertatug rezetecan (Mo-Rez) is moving into a Phase 3 program spanning platinum-resistant, platinum-sensitive ovarian cancer and 1L maintenance options for HRD-negative patients (i.e., those typically ineligible for PARP inhibitors), underscoring an overarching ambition to address the unmet needs in ovarian cancer
- DESTINY: AstraZeneca/Daiichi Sankyo’s HER2-directed ADC trastuzumab deruxtecan (T-DXd; Enhertu) received a tumor-agnostic accelerated approval in HER2-positive solid tumors, but was restricted to patients with HER2 IHC 3+ expression. T-DXd is now being evaluated in the 1LM setting across a broader HER2-expressing population (IHC 1+ to 3+), reflecting efforts to expand use beyond the current narrow label
- REJOICE: Daiichi Sankyo/Merck’s CDH6-directed ADC raludotatug deruxtecan (R-DXd) is being advanced through the global Phase 2/3 studies in platinum-resistant ovarian cancer, regardless of CDH6 expression status.
- TREVI: AstraZeneca’s FRα-directed ADC torvutatug samrotecan (Torvu-Sam) is being tested across both FRα-high and FRα-low platinum-resistant disease. In FRα-high disease, the trial is a direct head-to-head against Elahere, making it one of the clearest tests of whether a next-generation FRα ADC can displace current ADCs.
- FRAmework: Lilly’s FRα-directed ADC sofetabart mipitecan (Sofe-M) has accelerated directly from Phase 1 into a Phase 3 trial as the space grows increasingly competitive, aiming to capture both PARPi-treated and PARPi-naive recurrent disease.
- TroFuse: Merck’s TROP2-directed ADC sacituzumab tirumotecan (sac-TMT) is being evaluated in TroFuse-022 as maintenance therapy in both 1L and 2L settings. The ovarian program builds on established activity across lung, breast, and other solid tumors
Together, these programs show that ADC developers are no longer only asking whether these agents can work in biomarker-selected patients, but whether they can move earlier in treatment and expand benefit across broader populations, including PSOC, maintenance, and even neoadjuvant/adjuvant settings. As ADCs move into earlier lines, differentiation will depend not only on target selection, but also on safety and tolerability, particularly as payload-driven toxicities including ILD, hematologic toxicities, and ocular events continue to emerge.
Overall, inequitable access to biomarker testing remains a major barrier in ovarian cancer globally, increasing the need for therapies that can benefit broader patient populations regardless of biomarker status, which is the direction ADC development is headed. Ensuring equitable global access to these novel therapies will be critical to translating these advances into meaningful outcomes for all women, so that no woman is left behind.
