Across 371 European CTIS Phase II and Phase III lung cancer trial records, objective response rate / overall response (ORR/OR) is the most frequent endpoint family overall, appearing in 284 records (76.5%) and as a primary endpoint in 174 records (46.9%). Phase II is response-led, with ORR/OR primary in 131 of 221 records (59.3%), while Phase III is survival-led, with progression-free survival (PFS) primary in 66 of 150 records (44.0%) and overall survival (OS) primary in 55 of 150 records (36.7%).
The four most frequently measured endpoint families across any role were ORR/OR in 284 of 371 records (76.5%), OS in 272 (73.3%), safety/tolerability in 267 (72.0%), and PFS/PFS2 in 262 (70.6%). DOR was also common, appearing in 189 records (50.9%).
European lung cancer endpoint packages remain anchored in radiographic response and time-to-event survival. For CTIS/EU submissions, ORR, PFS, OS, DOR, and safety are the de facto core endpoint set.
ORR/OR was the leading primary endpoint family in 174 of 371 records (46.9%). Secondary endpoints were broader: ORR/OR appeared as secondary in 238 records (64.2%), OS in 230 (62.0%), PFS/PFS2 in 226 (60.9%), and safety/tolerability in 219 (59.0%). Exploratory/other endpoints were uncommon, appearing in 11 records (3.0%).
| Endpoint family | Primary | Secondary | Exploratory / other |
|---|---|---|---|
| ORR/OR | 174 / 46.9% | 238 / 64.2% | 2 / 0.5% |
| PFS/PFS2 | 106 / 28.6% | 226 / 60.9% | 2 / 0.5% |
| Safety / tolerability | 96 / 25.9% | 219 / 59.0% | 7 / 1.9% |
| OS | 80 / 21.6% | 230 / 62.0% | 1 / 0.3% |
| DOR | 7 / 1.9% | 187 / 50.4% | 0 / 0.0% |
| Patient-reported outcomes / QoL | 5 / 1.3% | 132 / 35.6% | 6 / 1.6% |
| PK | 19 / 5.1% | 111 / 29.9% | 1 / 0.3% |
| Biomarkers / molecular testing | 20 / 5.4% | 53 / 14.3% | 7 / 1.9% |
ORR is the main primary-endpoint workhorse, especially for Phase II expansion and activity studies. Secondary endpoint packages are much more standardized around OS, PFS, safety, DOR, QoL, PK, and immunogenicity.
In Phase II records, ORR/OR was primary in 131 of 221 records (59.3%), followed by safety/tolerability in 85 (38.5%). In Phase III records, PFS/PFS2 was primary in 66 of 150 records (44.0%), OS in 55 (36.7%), and ORR/OR in 43 (28.7%).
Phase II lung cancer trials are still optimized for antitumor activity and dose/safety confidence. Phase III submissions move toward regulatory survival anchors, especially PFS and OS, with DFS/EFS emerging in earlier-stage and perioperative studies.
Non-small cell lung cancer (NSCLC) accounted for 319 of 371 records (86.0%), while small cell lung cancer (SCLC) accounted for 41 records (11.1%). NSCLC primary endpoints were led by ORR/OR in 151 of 319 records (47.3%) and PFS in 92 (28.8%); SCLC primary endpoints were led by ORR/OR in 18 of 41 (43.9%) and OS in 16 (39.0%).
| Group | Records | Leading primary endpoint families |
|---|---|---|
| NSCLC | 319 / 86.0% | ORR/OR 151 (47.3%); PFS 92 (28.8%); safety 80 (25.1%); OS 62 (19.4%) |
| SCLC | 41 / 11.1% | ORR/OR 18 (43.9%); OS 16 (39.0%); PFS 12 (29.3%); safety 12 (29.3%) |
| Advanced / metastatic disease | 143 / 38.5% | ORR/OR 72 (50.3%); PFS 45 (31.5%); safety 40 (28.0%); OS 38 (26.6%) |
| Early / resectable or locally advanced | 40 / 10.8% | PFS 14 (35.0%); ORR/OR 13 (32.5%); pCR/MPR 7 (17.5%); DFS/EFS 7 (17.5%) |
| EGFR-mutant disease | 34 / 9.2% | PFS 14 (41.2%); ORR/OR 12 (35.3%); PK 6 (17.6%); safety 6 (17.6%) |
NSCLC endpoint strategy largely mirrors the overall dataset because it dominates the cohort. SCLC shows a stronger OS signal among primary endpoints, while earlier-stage and resectable studies add DFS/EFS and pathological response endpoints to the usual ORR/PFS backbone.
Modality groups were non-mutually exclusive because combination trials often included multiple drug classes. Small molecules appeared in 251 records (67.7%), monoclonal antibodies in 214 (57.7%), antibody-drug conjugates (ADCs) in 69 (18.6%), and bispecific antibodies in 35 (9.4%). ADC-containing trials were especially ORR-heavy, with ORR/OR primary in 44 of 69 records (63.8%).
ADC-containing lung cancer trials lean more strongly toward ORR as a primary endpoint than small-molecule, monoclonal-antibody, or bispecific-antibody records. This fits an activity-demonstration strategy where radiographic response is central before larger survival-confirmatory programs.
Patient-reported outcomes / quality of life (QoL) appeared in 139 of 371 records (37.5%) but were primary in only 5 records (1.3%), confirming their role as secondary evidence. Biomarker or molecular testing endpoints appeared in 68 records (18.3%), while RECIST was referenced in 244 records (65.8%) and blinded independent central review / BIRC / BICR in 95 records (25.6%).
For CTIS submissions, RECIST-based radiographic assessment remains central, while QoL and biomarkers usually support rather than replace the primary endpoint. BICR is especially important in Phase III, where independent review appears in primary endpoint text for one-third of records.
Trial records averaged 1.66 primary endpoint entries, 6.42 secondary endpoint entries, and 0.06 exploratory/other endpoint entries. Multi-primary designs appeared in 140 of 371 records (37.7%), including 94 of 221 Phase II records (42.5%) and 46 of 150 Phase III records (30.7%). The median interval from initial CTIS submission to first authorization was 95 days overall.
CTIS lung cancer submissions usually present a dense secondary endpoint architecture, while explicitly exploratory/other endpoint fields are rare. Phase III records have a longer median authorization interval than Phase II, consistent with more confirmatory survival-oriented packages.
ORR/OR = objective response rate / overall response. PFS = progression-free survival. OS = overall survival. DOR = duration of response. DCR/DC = disease control rate / disease control. DFS/EFS = disease-free survival / event-free survival. pCR/MPR = pathologic complete response / major pathologic response. PK = pharmacokinetics. QoL = quality of life. RECIST = Response Evaluation Criteria in Solid Tumors. BICR/BIRC = blinded independent central review / blinded independent review committee. CTIS = Clinical Trials Information System.