Across 47 European CTIS Phase II & III endometrial/uterine cancer trials, endpoint strategy is split between response-driven Phase II development and survival-driven Phase III confirmation. Primary endpoints were led by objective response rate (ORR) in 19/47 trials (40.4%) and safety/dose-finding in 17/47 (36.2%), while Phase III primary endpoints shifted strongly toward overall survival (OS) in 11/18 trials (61.1%) and progression-free survival (PFS) in 10/18 (55.6%).
The endpoint inventory contained 86 primary endpoint entries, 311 secondary endpoint entries, and 2 explicitly exploratory endpoint entries. At trial level, ORR was the most common primary endpoint family, while safety and ORR were tied as the most common secondary endpoint families.
European CTIS endometrial/uterine cancer protocols most often use ORR and safety to make the primary development decision, then surround that decision with secondary survival, response durability, disease control, PK, QoL, and immunogenicity endpoints.
Phase II trials accounted for 29/47 studies (61.7%) and were dominated by primary ORR in 18/29 trials (62.1%) and safety/dose-finding in 14/29 (48.3%). Phase III trials accounted for 18/47 studies (38.3%) and shifted to primary OS in 11/18 trials (61.1%) and primary PFS in 10/18 (55.6%).
The CTIS/EU pattern is clear: Phase II protocols mostly test whether a therapy produces measurable tumour response and acceptable safety, while Phase III protocols anchor the primary regulatory question in OS and PFS.
Endometrial-only studies represented 19/47 trials (40.4%), while multi-tumour basket studies including endometrial cancer represented 28/47 (59.6%). Endometrial-only trials used primary PFS and OS more often, while basket trials relied more on ORR and safety/dose-finding.
| Disease setting | Trials | Top primary endpoint pattern |
|---|---|---|
| Endometrial-only | 19 / 47 · 40.4% | PFS 9/19 (47.4%) and OS 9/19 (47.4%) |
| Basket / multi-tumour | 28 / 47 · 59.6% | ORR 16/28 (57.1%) and safety 14/28 (50.0%) |
Endometrial-only CTIS submissions look more confirmatory, with PFS/OS as leading primary endpoints. Basket trials including endometrial cancer are more signal-seeking, with ORR and safety/dose-finding dominating primary endpoint choices.
Three modality groups were large enough for comparison: small molecules appeared in 29/47 trials (61.7%), monoclonal antibodies in 18/47 (38.3%), and antibody-drug conjugates (ADCs) in 14/47 (29.8%). Trials may include more than one modality, so modality denominators overlap.
| Modality | Trials | Most common primary endpoint families | Notable secondary signal |
|---|---|---|---|
| Small molecule | 29 | OS 12/29 (41.4%); PFS 11/29 (37.9%) | DOR 23/29 (79.3%) |
| Monoclonal antibody | 18 | ORR 8/18 (44.4%); OS/PFS/safety 6/18 each (33.3%) | Secondary ORR 16/18 (88.9%) |
| ADC | 14 | Safety 7/14 (50.0%); OS and ORR 6/14 each (42.9%) | PK 9/14 (64.3%) |
ADC trials carry the heaviest safety and PK endpoint burden, while monoclonal antibody trials most consistently keep ORR in the endpoint package. Small-molecule studies are more balanced between survival endpoints and response/durability endpoints.
The 47-trial EU CTIS cohort was weighted toward 2024 authorizations, with 27/47 trials (57.4%) in 2024, 12/47 (25.5%) in 2025, and 8/47 (17.0%) in 2026. Across the CTIS period, Phase III submissions consistently used PFS/OS as the primary confirmatory anchor.
For sponsors preparing EU CTIS submissions in endometrial/uterine cancer, the practical benchmark is a two-layer package: ORR/safety for Phase II decision-making and PFS/OS for Phase III confirmation, with DOR, DCR, QoL, PK, ADA, and biomarker endpoints used as supporting evidence.
The same endpoint data also show how often trials include patient-reported outcomes, biomarker endpoints, and explicitly exploratory endpoint packages.
QoL has become a meaningful secondary endpoint layer, especially in Phase III where it appeared in 10/18 trials (55.6%). Exploratory endpoints were rarely labelled as such, so biomarker work is usually embedded inside secondary endpoint packages rather than separated into an exploratory section.
ORR = objective response rate; PFS = progression-free survival; OS = overall survival; DOR = duration of response; DCR = disease control rate; QoL = quality of life; PRO = patient-reported outcome; PK = pharmacokinetics; ADA = anti-drug antibody; ADC = antibody-drug conjugate; CTIS = Clinical Trials Information System.