Clinical Trial Intelligence

Which Endpoints Are Measured Most Often in European Phase II & III Lymphoma Trials?

11 July 2026

Across 224 CTIS phase-listed European lymphoma Phase II and Phase III trial entries from 2024–2026, the most frequently measured endpoint families were overall survival (OS) in 173 entries (77.2%), safety/adverse events in 167 (74.6%), progression-free survival (PFS) in 165 (73.7%), objective/overall response rate (ORR) in 157 (70.1%), and complete response/remission in 151 (67.4%). The endpoint strategy differs sharply by phase: Phase II primary endpoints are response-led, while Phase III primary endpoints are dominated by PFS.

224
CTIS phase-listed lymphoma entries
173
entries measured OS
75
used CR/CRR as primary endpoint family
48/73
Phase III entries used PFS as a primary endpoint family

Which endpoint families appear most often overall?

OS was the most frequently measured endpoint family, appearing in 173 of 224 CTIS entries (77.2%). Safety/adverse events followed closely at 167 entries (74.6%), PFS at 165 (73.7%), ORR at 157 (70.1%), and complete response/remission at 151 (67.4%). Endpoint categories are trial-level presences and can overlap when one endpoint measures several related constructs.

Endpoint family present anywhere in the trial record
Overall survival (OS)77.2%
Safety / adverse events74.6%
Progression-free survival (PFS)73.7%
Objective / overall response rate (ORR)70.1%
Complete response / remission67.4%
Duration of response (DOR)52.7%
Quality of life / patient-reported outcomes40.2%
Pharmacokinetics (PK)27.7%
Percentages use 224 CTIS Phase II/III lymphoma entries as denominator.
Interpretation

European lymphoma CTIS submissions are not dominated by a single endpoint; they use a dense efficacy-and-safety package. OS, safety, PFS, ORR, and CR/CRR each appear in more than two-thirds of entries, suggesting that even response-driven lymphoma programs routinely retain survival and safety endpoints for regulatory comparability.

How do primary, secondary, and exploratory endpoints differ?

Primary endpoint fields were present in 210 of 224 entries (93.8%), secondary endpoint fields in 195 (87.1%), and formal other/exploratory endpoint fields in 11 (4.9%). Primary endpoints were led by complete response/remission in 75 entries (33.5%), PFS in 72 (32.1%), ORR in 67 (29.9%), and safety in 60 (26.8%). Secondary endpoints were led by OS in 169 entries (75.4%) and safety in 139 (62.1%).

Top endpoint families by official endpoint role
Primary
CR/CRR: 75 (33.5%)
PFS: 72 (32.1%)
ORR: 67 (29.9%)
Safety: 60 (26.8%)
OS: 31 (13.8%)
Secondary
OS: 169 (75.4%)
Safety: 139 (62.1%)
ORR: 137 (61.2%)
CR/CRR: 131 (58.5%)
PFS: 128 (57.1%)
Other / exploratory
Biomarkers / PD: 7 (3.1%)
QoL / PRO: 6 (2.7%)
Safety: 5 (2.2%)
PFS: 4 (1.8%)
MRD: 3 (1.3%)
CR/CRR = complete response / complete response rate; PD = pharmacodynamics; MRD = measurable/minimal residual disease.
Interpretation

The primary endpoint layer is split between response and time-to-event efficacy, while the secondary layer carries the broader regulatory evidence package. Formal exploratory endpoint fields are rare in CTIS lymphoma records, but biomarker, pharmacodynamic, QoL, and MRD concepts still appear frequently inside secondary endpoint structures.

How do Phase II and Phase III lymphoma endpoint strategies differ?

The cohort contained 151 Phase II-listed entries (67.4%) and 73 Phase III-listed entries (32.6%). In Phase II, primary endpoints were response-led: CR/CRR appeared in 69 of 151 entries (45.7%), ORR in 60 (39.7%), and safety in 55 (36.4%). In Phase III, PFS became the dominant primary endpoint, appearing in 48 of 73 entries (65.8%), ahead of OS in 18 (24.7%).

Primary endpoint families by phase
Endpoint family Phase II Phase III
PFS24/151 (15.9%)48/73 (65.8%)
CR/CRR69/151 (45.7%)6/73 (8.2%)
ORR60/151 (39.7%)7/73 (9.6%)
Safety / AEs55/151 (36.4%)5/73 (6.8%)
OS13/151 (8.6%)18/73 (24.7%)
Phase II denominator: 151 entries; Phase III denominator: 73 entries.
Interpretation

Phase II lymphoma submissions emphasize early efficacy and tolerability signals, especially CR/CRR, ORR, and safety. Phase III submissions shift toward comparative time-to-event evidence, with PFS appearing as a primary endpoint family in nearly two-thirds of Phase III entries.

Which lymphoma subtypes have enough entries for endpoint comparison?

Subtype mentions were sufficient for comparison in diffuse large B-cell / large B-cell lymphoma (72 entries), Hodgkin lymphoma (58), CLL/SLL (45), follicular lymphoma (45), mantle cell lymphoma (31), T-cell lymphoma (22), and marginal zone lymphoma (15). Because some CTIS disease fields include multiple lymphoma diagnoses, subtype groups are mention-based and can overlap.

Top overall endpoint families within major lymphoma subtypes
Subtype n Most frequent endpoint families
DLBCL / large B-cell72PFS 57 (79.2%); OS 55 (76.4%); ORR 53 (73.6%); CR 53 (73.6%)
Hodgkin lymphoma58OS 44 (75.9%); safety 43 (74.1%); PFS 40 (69.0%); ORR 39 (67.2%)
CLL/SLL45Safety 34 (75.6%); PFS 33 (73.3%); ORR 33 (73.3%); OS 33 (73.3%)
Follicular lymphoma45CR 38 (84.4%); ORR 37 (82.2%); OS 36 (80.0%); PFS 35 (77.8%)
Mantle cell lymphoma31PFS 23 (74.2%); safety 23 (74.2%); ORR 22 (71.0%); CR 22 (71.0%)
T-cell lymphoma22CR 19 (86.4%); OS 18 (81.8%); ORR 17 (77.3%); safety 16 (72.7%)
Marginal zone lymphoma15CR 14 (93.3%); PFS 13 (86.7%); OS 13 (86.7%); safety 12 (80.0%)
Subtype groups are based on CTIS disease-field mentions; entries may appear in more than one subtype group.
Interpretation

Across lymphoma subtypes, the common evidence package remains stable: response, PFS, OS, and safety dominate. The clearest subtype-specific signal is that follicular, T-cell, and marginal zone lymphoma entries are especially response/remission-heavy, while DLBCL / large B-cell entries are more PFS-led.

Do drug modalities change endpoint selection?

Modality comparisons were numerically strongest for small molecules (158 entries), monoclonal antibodies (130), bispecific antibodies (44), cell therapy (32), and antibody-drug conjugates (ADCs; 27). Small-molecule and monoclonal-antibody entries were PFS-led at the primary endpoint level, while cell-therapy entries had the strongest primary safety signal.

Primary endpoint leaders in modality groups with ≥20 entries
Modality n Leading primary endpoint families
Small molecule158PFS 65 (41.1%); ORR 42 (26.6%); CR 42 (26.6%)
Monoclonal antibody130PFS 52 (40.0%); CR 35 (26.9%); ORR 31 (23.8%)
Bispecific antibody44CR 14 (31.8%); ORR 12 (27.3%); safety 12 (27.3%)
Cell therapy32Safety 15 (46.9%); ORR 12 (37.5%); CR 12 (37.5%)
ADC27CR 11 (40.7%); ORR 9 (33.3%); PFS 8 (29.6%)
Modality groups are based on CTIS drug-modality fields; entries can include multiple modalities.
Interpretation

Endpoint selection is partly modality-sensitive. Small-molecule and antibody programs look closer to conventional late-stage lymphoma designs with PFS prominent as a primary endpoint, while cell therapy and ADC entries retain stronger early efficacy and safety orientation.

What CTIS and EU submission patterns are visible?

All 224 entries were grouped by first CTIS authorization year: 168 entries were authorized in 2024, 47 in 2025, and 9 in 2026. The median interval from initial CTIS submission to first authorization was 55 days overall. The median interval was 54 days for Phase II entries and 60 days for Phase III entries.

CTIS entries by first authorization year and median submission-to-authorization interval
Entries by authorization year
2024168 (75.0%)
202547 (21.0%)
20269 (4.0%)
Median CTIS interval
55 days
Overall median from initial CTIS submission to first authorization.
Phase II: 54 days
Phase III: 60 days
CTIS = Clinical Trials Information System. Interval calculated from available initial CTIS submission and first authorization dates.
Interpretation

For EU lymphoma submissions in this dataset, Phase III authorization timing was only modestly longer than Phase II. This suggests that endpoint complexity alone does not strongly separate CTIS processing timelines between Phase II and Phase III lymphoma programs.

What adjacent endpoint questions can be answered from the same data?

The same CTIS endpoint data can answer several adjacent questions numerically: how often lymphoma trials include patient-reported outcomes, how often MRD is used, how often pharmacokinetics and immunogenicity are measured, and whether orphan or pediatric entries differ from the adult/non-orphan endpoint pattern.

Additional answerable endpoint questions from the same CTIS fields
90/224
included QoL or patient-reported outcome endpoints (40.2%).
52/224
included MRD or molecular response/remission endpoints (23.2%).
62/224
included pharmacokinetic endpoints (27.7%).
36/224
included immunogenicity / anti-drug antibody endpoints (16.1%).
68/224
were orphan-drug entries; their most frequent overall endpoints were OS and PFS, both 59/68 (86.8%).
29/224
were pediatric entries; safety appeared in 24/29 (82.8%) and OS in 22/29 (75.9%).
Adjacent questions are restricted to fields available in the endpoint extract and CTIS context variables.
Interpretation

The dataset supports more than endpoint ranking: it also quantifies the penetration of patient-reported, molecular, PK, immunogenicity, orphan, and pediatric endpoint strategies. These are useful adjacent angles for EU submission planning because they show which supportive measures are becoming common in CTIS lymphoma dossiers.

Definitions

PFS = progression-free survival; OS = overall survival; ORR = objective or overall response rate; CR/CRR = complete response or complete response rate; DOR = duration of response; EFS = event-free survival; MRD = measurable or minimal residual disease; QoL = quality of life; PRO = patient-reported outcome; PK = pharmacokinetics; ADA = anti-drug antibody; ADC = antibody-drug conjugate; CTIS = Clinical Trials Information System.