Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer (NCT03310957), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The central clinical question is therefore about the safety profile observed among participants receiving the combination, not whether the combination performs better than another treatment. A single-group study can describe adverse events in the treated population, but it cannot by itself isolate the effect of the combination from the underlying disease, other circumstances, or the individual contributions of the two drugs.

The study title refers to first-line treatment, and the official title describes a phase 1b/2 study in patients with unresectable locally advanced or metastatic disease. The brief summary states that the trial was intended to examine both side effects and whether the drugs work. However, the posted results contain safety counts, while efficacy estimates for duration of response, disease control, progression-free survival, and overall survival are not reported in the registry record. Those questions cannot be answered from the safety counts alone.

3. Trial Design

This was a phase 1b/2, single-group, open-label study of ladiratuzumab vedotin plus pembrolizumab. The registry records no allocation and no masking. Because there is no concurrent control arm, the study was not designed as a randomized comparison of the combination against another treatment. The study status is completed, and the registry lists enrollment of 185.

The trial record divides treatment into Parts A, B, C, and D, with dose levels and schedules varying by part. Parts A and B include SGN-LIV at 2.0 mg/kg and 2.5 mg/kg on a Q3WK schedule. Part C includes 1.0 mg/kg and 1.25 mg/kg on a Q1WK schedule, while Part D lists 1.5 mg/kg on a 2Q3WK schedule. These group descriptions show that the safety information comes from more than one regimen. They do not create randomized comparison groups, and differences between groups should not be read as causal dose effects.

The primary safety population included participants who received any amount of SGN-LIV1A or pembrolizumab. The registry says that, as specified in the statistical analysis plan, data were summarized by dose levels; it also says the shared 2.0 mg/kg and 2.5 mg/kg dose levels in Parts A and B were combined across those arms. The posted adverse-event groups are labelled by part and regimen, so interpretation should follow the group descriptions attached to each reported count rather than treating the groups as a randomized sequence.

The primary completion date is 2024-09-30, and the registry gives a start date of 2018-02-27. The record lists 11 outcome measures and no analyses. A detailed account of the protocol’s allocation procedures beyond the single-group designation, the rationale for each dose schedule, and the statistical plan beyond the stated safety-population description is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Participants were enrolled into Part A, Part B, Part C, and Part D sequentially.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all participants who received any amount of SGN-LIV1A or pembrolizumab. As pre-specified in the SAP, data was summarized by dose levels. Since Arm A and Arm B share the same dose levels (2.0 mg/kg and 2.5 mg/kg), these dose levels were combined across both arms.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: As pre-specified in the statistical analysis plan (SAP), data was summarized by dose levels. Since Arm A and Arm B share the same dose levels (2.0 mg/kg and 2.5 mg/kg), these dose levels were combined across both arms.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over From start of study treatment up to 30 days and up to 90 days post last dose for AEs and SAEs respectively (maximum exposure to any study treatment = 27 months; follow-up: AEs = maximum up to 28 months; SAEs = maximum up to 30 months).

The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). It is a participant-count endpoint: it counts people who experienced an event, rather than the total number of event episodes. A participant can experience more than one event, so participant counts do not describe the full event burden or how often events recurred.

The record defines an adverse event as an untoward medical occurrence after administration of a medicinal product, whether or not it is considered causally related to treatment. A TEAE is an event that was newly occurring or worsened after the first dose, within the stated period after the last dose. The adverse-event window is up to 30 days after the last dose; for SAEs, the stated window extends up to 90 days after the last dose. The record gives maximum exposure to any study treatment as 27 months, and maximum follow-up as 28 months for AEs and 30 months for SAEs.

SAEs are defined by seriousness criteria that include death, a life-threatening event, inpatient hospitalization or prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, and other medically significant events. SAEs are included among AEs, alongside non-serious events. Reporting both categories helps distinguish events meeting those seriousness criteria from the broader set of treatment-emergent events. Neither category, by itself, proves that treatment caused an event.

Safety counts are used in early-phase and combination-treatment studies to describe observed tolerability and identify events that warrant attention in further evaluation. They do not provide a controlled estimate of treatment-attributable risk in this single-group design.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent? A participant count records whether a person experienced at least one event meeting the endpoint definition. It is different from an event count, which can include repeated episodes in one person. The primary endpoint is explicitly a count of participants. This makes the measure interpretable as the number of people affected in each reported group, but it does not show event duration, recurrence, severity beyond the separate SAE classification, or the distribution of multiple events within individuals.

What is the distinction between an AE, TEAE, and SAE? In general, an adverse event is a medical occurrence during a study and need not be caused by treatment. A treatment-emergent definition focuses on events that begin or worsen after treatment starts within a specified observation window. Seriousness is a separate classification based on outcomes or medical significance, not simply how intense a symptom feels. In this record, AEs include both serious and non-serious events. The TEAE and SAE windows are stated separately, so the period used to capture an event matters when comparing counts across studies.

Why are the groups not a dose-response experiment? The registry lists several regimen groups across study parts, but the overall design is single-group and does not use random allocation. In general, randomization helps balance known and unknown participant characteristics between treatment groups. Without it, differences in observed counts may reflect differences in who entered each part, when the part was conducted, how long participants were exposed or followed, or other factors. The record does not provide a controlled estimate that separates these possibilities. A numerical contrast between two groups would therefore be descriptive, not a causal treatment effect.

How should percentages and counts be read? A proportion uses a group denominator and a count of participants meeting a definition. It can be useful for conveying how common an outcome was within a group, but its precision depends on the amount of information in that group and on the event definition and follow-up. Small groups can produce especially unstable proportions. The registry’s safety counts and serious-term percentages should be read within their stated group and reporting context. They should not be combined or turned into a single overall estimate unless the record specifies a valid analysis and denominator. No such overall estimate is reported in the registry record.

What would a confidence interval add? In general, a confidence interval describes the uncertainty around an estimated quantity under a statistical model and analysis procedure. It can show which values remain reasonably compatible with the observed data, rather than presenting a point estimate as exact. The registry summary does not report confidence intervals for the adverse-event counts. Without them, the counts remain useful descriptions, but their statistical precision cannot be assessed from the posted summary alone.

What is over-dispersion, and does it apply? In general, over-dispersion arises when observed variability is greater than a model expects, often because observations are more heterogeneous or dependent than assumed. It is relevant to some count models, where failure to allow extra variability can make uncertainty appear too small. This endpoint is described as a count of participants with an event, rather than a count of repeated event episodes. The registry does not report a count-model analysis, a dispersion estimate, or a model-based uncertainty assessment. There is therefore no basis in the record to claim that over-dispersion was assessed or corrected.

How should planning illustrations be interpreted? Sample-size calculations based on an observed effect are planning illustrations, not observed trial outcomes and not evidence that the study had a particular power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the described planning quantity is a total number of events; for other outcomes, it is participants per arm for 80% or 90% power where those planning rows are shown. Such assumptions do not describe this single-group trial’s actual design. The registry record does not report that these were the trial’s own design assumptions, nor does it provide a sample-size justification in the trial record. Any planning calculation should be read as hypothetical rather than as observed power.

What analyses are reported? The record lists 11 outcome measures and no analyses. It provides the safety endpoint definitions, safety-population description, and adverse-event counts, but does not report inferential tests or adjusted estimates for these safety results. General statistical interpretation should therefore remain descriptive. The absence of a reported test does not establish that no analysis was conducted outside the registry; it means the analysis is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes: duration of response per RECIST v1.1, disease control rate, progression-free survival, and overall survival. It also lists 11 outcome measures and no analyses. Results for these secondary outcomes are not reported in the registry record. The record does not report whether a testing hierarchy, family-wise error control, false-discovery procedure, or another multiplicity strategy was prespecified. When many outcomes are examined, the chance of at least one apparently notable finding can increase; in general, prespecified methods help readers understand how that issue was handled. No such method can be attributed to this trial from the registry summary.

Missing-data procedures are not reported in the registry record. The summary does not describe how participants with incomplete follow-up, treatment discontinuation, or unavailable outcome assessments were handled for efficacy outcomes. For safety, the stated population includes participants who received any amount of SGN-LIV1A or pembrolizumab. The record does not give a detailed accounting of participants excluded from specific safety summaries or explain how incomplete safety follow-up affected the counts. Thus, the posted denominators should be read as the denominators attached to each listed regimen, not as a complete account of missingness or follow-up.

The registry states that the safety data were summarized by dose levels and that the shared dose levels in Parts A and B were combined across both arms as specified in the statistical analysis plan. However, the record does not report the analysis plan itself, the handling of participants who changed dose, or the exact derivation of each posted group beyond the labels and safety-population definition. It also does not report a complete analysis-population flow. These omissions limit assessment of whether all outcomes used the same population and observation rules.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (33.3%), abdominal pain (16.7%), ileus (16.7%), headache (16.7%), anaemia (14.3%).

Each serious-adverse-event figure is a participant count paired with the number at risk in that regimen group. For example, the registry reports 4 of 7 participants with a serious adverse event in Part A at 2.0 mg/kg Q3WK, and 14 of 37 in Part D at 1.5 mg/kg 2Q3WK. These are within-group descriptions. They are not randomized comparisons, and the numerical differences should not be interpreted as evidence that one regimen caused more or fewer serious events than another.

Seriousness follows the registry’s criteria, which include death, life-threatening events, hospitalization, significant disability or incapacity, congenital anomaly or birth defect, and other medically significant events. A serious event is not automatically treatment-related. The definition of an AE explicitly does not require a causal relationship with study treatment. The posted summary does not provide event-by-event causality assessments, timing, duration, or severity grades for each group.

The separate death counts do not establish that deaths were caused by treatment. The record does not report their causes or the relationship of each death to treatment in this summary. Similarly, the serious-event term percentages are not a substitute for a full account of the number of affected participants or their clinical context. Read the counts as descriptive safety observations within the record’s specified follow-up, not as comparative risk estimates or causal conclusions.

12. What the Result Does, and Does Not, Mean

The results show that adverse events, including serious adverse events, were recorded among participants treated with ladiratuzumab vedotin and pembrolizumab. The registry reports participant counts for serious and other adverse events across multiple dose and study-part groups, as well as percentages for selected serious-event terms. These findings describe what was recorded in the study’s safety population under the stated event definitions and follow-up windows.

They do not show whether the combination is more or less safe than another treatment, because the study has no concurrent control group and no randomized allocation. The groups differ by study part and regimen, so their counts do not provide a fair treatment comparison. Nor do the counts establish that a particular event was caused by either drug: the registry defines adverse events without requiring a causal relationship, and the posted summary does not provide detailed causality assessments.

The counts also do not answer whether the combination treats the cancer. The registry lists response, disease control, progression-free survival, and overall survival outcomes, but those results are not reported in the registry record. The trial’s stated interest in efficacy is not itself evidence of an efficacy result. Likewise, the death counts are not a survival analysis and cannot be interpreted as a treatment effect without relevant timing, cause, follow-up, and comparison information.

In general, an observed count is a description of the participants included in that safety summary. Its meaning depends on the denominator, outcome definition, observation period, and completeness of follow-up. The available record gives some of this context, but does not report confidence intervals or a detailed missing-data analysis. The appropriate conclusion is therefore limited: adverse events were observed and tabulated in this single-group study, while comparative safety, causal attribution, and efficacy remain unresolved by the posted results.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how safety questions differ from comparative treatment questions. A single-group phase 1b/2 design can collect structured information about events during exposure and follow-up, including events meeting formal seriousness criteria. Counts by regimen can help describe the safety experience within the groups that were studied. They do not, however, remove the need for a concurrent comparator when the goal is to estimate whether one treatment changes the probability of an outcome relative to another.

The regimen structure also matters for interpretation. Different study parts used different doses or schedules, while the record says some shared dose levels across Parts A and B were combined in the planned summaries. This means that group labels and population definitions are central to understanding what each count represents. Treating all groups as interchangeable, or as a randomized dose ladder, would obscure the design and could produce misleading conclusions.

Another important statistical distinction is between event counts and affected-participant counts. The primary endpoint counts participants with events, so repeated events in one participant are not represented as multiple affected people. This is a common and useful safety summary, but it does not convey every dimension of event burden. Separate descriptions of timing, recurrence, severity, and attribution would be needed for a fuller clinical interpretation, and those details are not reported in the registry summary.

Finally, the record illustrates why trial registration and posted results should be read as separate kinds of information. The registry states the intended safety and efficacy questions and lists multiple outcomes, but it does not report analyses for those outcomes. The safety counts can be described, while efficacy and comparative conclusions cannot be reconstructed from the listed outcome names alone. Distinguishing what is observed from what remains unreported is essential to sound statistical interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation is the absence of a concurrent control group. Adverse-event counts in a single-group study cannot establish how many events would have occurred under another treatment or without the study treatment. The open-label design also means masking was not used, as recorded in the registry. The record does not report how knowledge of treatment assignment may have been addressed in event assessment.

There are multiple dose levels, schedules, and study parts. The groups are not randomized comparisons, and their participant characteristics, exposure, or follow-up may differ. The registry’s statement about combining shared dose levels in Parts A and B does not provide a complete explanation of how every displayed adverse-event group relates to each analysis. No adjusted comparisons or uncertainty intervals for the safety counts are reported.

The posted summary does not provide detailed event-level information, such as the timing and duration of each event, severity grades, recurrence, or causality assessments. Although death is included among SAE criteria and deaths are listed by group, the summary does not report causes or treatment relationships. The record also does not describe missing-data procedures or give a detailed flow of participants into each analysis population.

Finally, efficacy results for the listed response and survival outcomes are not reported in the registry record. This prevents assessment of the intended efficacy questions from the posted results. Enrollment and completion status alone do not resolve these statistical limitations or supply the missing outcome analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer — NCT03310957.
• Registry record last updated 2025-12-12; status last verified 2025-12.
• Results first posted 2025-12-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry identifies NCT03310957 as a completed phase 1b/2, single-group, open-label study of ladiratuzumab vedotin (SGN-LIV1A/LV) plus pembrolizumab for triple-negative breast cancer. It lists enrollment of 185, a start date of 2018-02-27, and primary completion on 2024-09-30. Treatment regimens varied across Parts A through D.

The primary endpoint counts participants with treatment-emergent adverse events and serious adverse events. The registry reports safety counts by regimen group and selected serious-event term percentages, with safety analyses defined for participants who received any amount of either study drug. The design has no concurrent control, so the group counts are descriptive rather than randomized comparisons.

The record lists duration of response, disease control rate, progression-free survival, and overall survival among secondary outcomes, but their results and analyses are not reported in the registry record. The posted safety data therefore support description of recorded events, not conclusions about comparative safety, treatment causality, or efficacy.