Mesothelin-Targeted Immunotoxin LMB-100 Alone or in Combination With Nab-Paclitaxel in People With Previously Treated Metastatic and/or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mesothelin-Targeted Immunotoxin LMB-100 Alone or in Combination With Nab-Paclitaxel in People With Previously Treated Metastatic and/or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing Solid Tumors (NCT02810418), a non-randomized phase 1, phase 2 study. The primary outcome is Objective Response (OR) (Partial Responses + Complete Responses) in Phase 2 Subjects of Short Infusion LMB-100+ Nab-paclitaxel.

2. Clinical Question

3. Trial Design

NCT02810418 is registered as a completed Phase Ib/II study sponsored by the National Cancer Institute. It began on 2016-08-03, with primary completion on 2019-01-02. The registry lists enrollment of 40. Its design is sequential and non-randomized, with no masking. The study therefore does not assign participants at random to concurrent treatment groups, and its arms do not constitute a randomized comparison.

The study included distinct treatment questions. Arm A evaluated short-infusion LMB-100 with nab-paclitaxel in pancreatic cancer. The Phase 1 portion examined dose levels, while the Phase 2 portion used the short-infusion combination to assess efficacy. Arm B examined continuous-infusion LMB-100, including a single-agent lead-in and a combination-therapy arm. Eligibility for Arm B included pancreatic cancer, mesothelioma, and other mesothelin-expressing solid tumors, whereas Arm A focused on advanced pancreatic cancer.

The stated primary endpoint is objective response among Phase 2 participants receiving short-infusion LMB-100 with nab-paclitaxel. It is assessed approximately 6 weeks after treatment begins and then every 6 weeks until progression or the start of a new treatment, up to 1 year. Secondary outcomes include progression-free survival, overall survival, disease control at the end of treatment, response outcomes in Phase 1 arms, and adverse events.

The registry record does not report the allocation of the overall enrollment across arms, a sample-size justification, or a statistical analysis plan. Detailed treatment delivery information is not fully available in the record excerpt. These gaps limit the ability to reconstruct precisely how each participant's treatment and follow-up contributed to each reported outcome.

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.

Only the first 6 of 7 groups are shown.

Arm A Dose Escalation

Reasons for not completing this period:

Dose Expansion

Reasons for not completing this period:

Arm B Dose Escalation

Reasons for not completing this period:

Arm B Combination Therapy

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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response (OR) (Partial Responses + Complete Responses) in Phase 2 Subjects of Short Infusion LMB-100+ Nab-paclitaxel, measured over Approximately 6 weeks after the start of treatment and continuing every 6 weeks until progression or start of a new treatment, up to 1 year.

The primary endpoint counts participants with an objective response in the Phase 2 short-infusion combination arm. The registry defines objective response as a partial response or complete response assessed using RECIST v1.1. A complete response means disappearance of all target lesions. A partial response requires at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference.

A response endpoint is useful because it applies predefined criteria to changes in tumor measurements. It distinguishes a response from other possible outcomes, such as stable disease or progression, and provides a direct count of participants meeting the response definition. It does not, by itself, describe how long a response lasts, whether participants live longer, or how symptoms change. Those are different clinical outcomes; the registry lists progression-free survival and overall survival as secondary outcomes.

The planned assessment begins approximately 6 weeks after treatment starts and continues every 6 weeks until progression or a new treatment, up to 1 year. The actual Phase 2 response count, response proportion, and uncertainty interval are not reported in the registry record. Thus the endpoint's definition and assessment schedule are available, but the primary efficacy result cannot be interpreted from the posted outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help frame this study, but they should not be mistaken for methods confirmed in its protocol. The statistical analysis plan is not reported in the registry record. The explanations below are general and describe why particular design and reporting details matter.

What does a response count represent?

A count records how many participants met the response definition. A response proportion would relate that count to the number of participants assessed in the relevant group. The registry names the Phase 2 short-infusion combination group as the population of interest, but it does not report the response count or the number assessed for that endpoint. It is therefore not possible to state a response proportion from the posted primary outcome.

Response criteria make the outcome more reproducible by specifying how tumor measurements translate into categories. Under the registry's RECIST v1.1 definition, complete response requires disappearance of all target lesions, and partial response requires at least a 30% decrease in the sum of target-lesion diameters from baseline. These criteria define which participants are counted as responders; they do not supply the observed result.

Why does the design matter?

Randomization is a general method for balancing known and unknown participant characteristics across treatment groups, on average. This study was non-randomized, so differences between groups may reflect who entered each group as well as the treatments and doses used. Sequential enrollment can also mean that treatment groups represent different stages or questions within a study. The registry describes the study as sequential but does not report enough detail to establish the exact enrollment sequence or how it affected analyses.

Masking is another design feature. The registry states that masking was absent. In general, knowledge of treatment assignment can influence care, outcome assessment, or reporting, depending on the outcome and study procedures. The record does not report whether response assessments were independently reviewed or otherwise protected from knowledge of treatment assignment.

What would an interval estimate add?

In general, a confidence interval conveys the uncertainty around an estimated outcome under the assumptions of the analysis. It helps distinguish a relatively precise estimate from one that is compatible with a broad range of values. The primary response estimate and its confidence interval are not reported in the registry record, so the precision of that result cannot be evaluated. A confidence interval would not, by itself, correct for the non-randomized design or make the arms comparable.

How should planning illustrations be understood?

The registry's planning assumptions describe illustrations based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning exercises: they ask what sample size might be needed under selected assumptions. They are not observed power, do not show what the trial actually achieved, and do not substitute for the trial's observed results. The sample-size justification used to design the trial is not reported in the registry record. No planning count should be interpreted as an observed number of participants or events.

More generally, a planning calculation depends on the effect used as its target, the outcome's variability or event frequency, the desired error rates, and the analysis model. Changing an assumption changes the planning result. These calculations are especially sensitive to uncertainty when the target effect comes from a small or non-randomized study. The posted record does not report a protocol-based justification that would allow readers to determine whether the study's enrollment was chosen for a particular power target.

Why can multiplicity matter?

Multiplicity arises when a study evaluates several outcomes, treatment arms, dose levels, or repeated opportunities for testing. In general, conducting many inferential tests can increase the chance of finding an apparently unusual result by chance if no adjustment or prioritization is used. The registry lists multiple secondary outcomes and several treatment arms, but its approach to multiplicity is not reported in the registry record. It is not possible to determine from the outcome list alone whether any multiplicity adjustment was planned or used.

Finally, analyses depend on clear population definitions and complete outcome data. The registry does not report the primary analysis population, the number assessed for response, missing-data handling, or the details of any sensitivity analyses. Those details matter because excluding participants or handling unassessed outcomes differently can change an estimate. In the absence of the primary result and these analysis details, interpretation should remain descriptive and limited to what the registry explicitly records.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response outcome alongside multiple secondary outcomes, including progression-free survival, overall survival, disease control, response outcomes in Phase 1 groups, and adverse events. It also describes several arms and dose levels. When multiple outcomes or comparisons are examined, multiplicity can affect how often apparently notable results arise by chance. In general, a prespecified testing hierarchy or adjustment can address this issue, but the registry does not report whether either was used.

The registry record also does not report a statistical analysis plan, the primary analysis population, or a detailed account of how missing outcome data were handled. It does not state how participants who stopped treatment, began another treatment, or lacked a scheduled response assessment were treated in the primary endpoint analysis. The endpoint assessment schedule is described, but that schedule alone does not reveal how incomplete follow-up was incorporated into the analysis.

These omissions matter because the count of participants with an observed response is not necessarily the same as the count that would result from different rules for unassessed participants. The number assessed for the primary endpoint is not reported in the registry record, and the response count itself is also not reported. No sensitivity analysis addressing missing data is described.

Without the analysis plan and outcome-level denominators, readers cannot verify the analysis population, assess the effect of missingness, or determine how multiple outcomes were handled. These limitations do not establish that the analyses were inappropriate; they mean that the relevant methods are not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death nos (33.3%), neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, death (33.3%), anemia (20.0%), blood bilirubin increased (20.0%), dizziness (20.0%).

The registry reports serious adverse event counts by treatment group. The counts of participants with serious adverse events are: 3 among 6 at risk in the Phase 1 short-infusion 100µg/kg LMB-100 group; 4 among 8 in the Phase 1 short-infusion 65µg/kg group; 1 among 6 in the Phase 2 short-infusion 65µg/kg group; 2 among 6 in the continuous-infusion single-agent 100µg/kg/day group; 2 among 3 in the continuous-infusion single-agent 65µg/kg/day group; 2 among 6 in the continuous-infusion single-agent 100µg/kg group; and 1 among 5 in the continuous-infusion combination group.

The registry also lists deaths by group: 5, 8, 5, 6, 3, 6, and 3, respectively, in the groups listed in the adverse-event record. The cause, timing, and treatment attribution of these deaths are not reported in the registry record. They should not be interpreted as treatment-caused deaths on the basis of these counts alone.

Listed serious-event terms include Death NOS and a neoplasm-related death term, each at 33.3%, and anemia, increased blood bilirubin, dizziness, and lower gastrointestinal hemorrhage, each at 20.0%. The denominator for these percentages and whether terms overlap across participants are not reported. Since the arms were not randomized, these counts do not support a comparative safety conclusion.

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

The trial addresses an important statistical distinction: a clearly defined endpoint is not the same as a reported endpoint result. The registry explains what counts as objective response and when response assessments were planned, but it does not report the Phase 2 response count, response proportion, or uncertainty interval. The primary efficacy finding therefore cannot be characterized from the registry record.

The study also examines more than one treatment approach. LMB-100 was studied with nab-paclitaxel in short-infusion arms and as continuous-infusion treatment, including a single-agent lead-in and a combination arm. These are distinct regimens and study questions. The primary endpoint applies to the Phase 2 short-infusion combination group, not to all participants or all arms.

Because allocation was non-randomized and the arms were not like-for-like controls, the study cannot establish a causal comparison between regimens by simply contrasting their outcomes. The available safety counts describe events recorded in the groups; they do not, on their own, show that a treatment caused an event or establish which regimen has a different safety profile.

The registry's enrollment figure and safety counts do not fill the gap in the primary response outcome. Nor do the listed secondary outcomes establish results when their outcome estimates are not reported. The study record therefore supports understanding of the design, eligibility scope, endpoint definition, and reported safety counts, but not a conclusion about the size or certainty of an efficacy effect.

This distinction is important for readers: absence of a reported result is not evidence that the endpoint had no responses or that a treatment had no effect. It means the response outcome is not available in the registry record for interpretation. Additional results and analysis details would be needed to judge the observed response pattern, its precision, and the handling of missing data.

13. Why This Trial Matters Statistically

This study is statistically notable for combining dose-finding and efficacy questions within a non-randomized, sequential design. Phase 1 arms explored different doses and infusion approaches, while the Phase 2 primary endpoint focused on the short-infusion LMB-100 and nab-paclitaxel combination. Keeping those questions separate is essential: dose-finding observations and the Phase 2 response endpoint do not represent interchangeable evidence.

The study also illustrates why endpoint definitions and endpoint results must be considered together. RECIST v1.1 provides explicit criteria for classifying complete and partial responses, including the required decrease from baseline for partial response. That clarity supports interpretation of what a response means, but it cannot replace the missing observed count, denominator, and estimate of uncertainty.

Its non-randomized structure is another important statistical feature. Without random allocation, treatment arms are not automatically comparable, particularly when regimens, dose levels, and eligible tumor types differ. A difference between groups would not isolate a treatment effect without further design and analysis support. The registry itself warns that the arms are not a like-for-like control comparison.

Finally, the record shows the value of transparent reporting. The enrollment, endpoint definition, assessment schedule, and selected adverse-event counts are recorded, while the primary efficacy result, analysis population, missing-data approach, multiplicity methods, and statistical analysis plan are not reported in the registry record. That boundary determines what can responsibly be inferred. The trial can be understood as a study of treatment approaches and outcome definitions, but its registry information does not permit a statistical assessment of the primary efficacy result.

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.

Several trial-specific limitations shape interpretation. First, the study was non-randomized and sequential, with no masking. Its treatment arms were not like-for-like controls, and the registry cautions against treating them as a control comparison. Differences across arms could reflect their distinct regimens, dose levels, eligibility criteria, or other factors; the registry does not report an analysis that separates those influences.

Second, the overall enrollment of 40 does not identify the number of participants in the Phase 2 primary endpoint group or the number assessed for response. Neither the primary response count nor an estimate with an uncertainty interval is reported in the registry record. This prevents assessment of the primary result and its precision.

Third, the study included different cancer populations across arms. Arm A focused on advanced pancreatic cancer, while Arm B also included mesothelioma and other mesothelin-expressing solid tumors. Results from one arm or population should not be assumed to apply to the others. The record does not report enough outcome-level detail to examine results by tumor type.

Fourth, key analytic details are not reported in the registry record: the sample-size justification, statistical analysis plan, analysis population, handling of missing response assessments, and approach to multiplicity. The safety record includes group counts and selected terms, but event attribution, timing, term denominators, and overlap between terms are not specified. These reporting gaps limit evaluation of efficacy and safety without establishing that the trial's conduct or analyses were deficient.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mesothelin-Targeted Immunotoxin LMB-100 Alone or in Combination With Nab-Paclitaxel in People With Previously Treated Metastatic and/or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing Solid Tumors — NCT02810418.
• Registry record last updated 2022-03-15; status last verified 2022-02.
• Results first posted 2021-02-02.
• 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

NCT02810418 is a completed, non-randomized, sequential Phase Ib/II study sponsored by the National Cancer Institute. It studied LMB-100 alone and with nab-paclitaxel in previously treated pancreatic cancer and mesothelin-expressing solid tumors. Registry enrollment is 40.

The primary endpoint was objective response in Phase 2 participants receiving short-infusion LMB-100 with nab-paclitaxel, defined using RECIST v1.1 and assessed approximately 6 weeks after treatment began, then every 6 weeks up to 1 year. The response result is not reported in the registry record.

The record lists serious adverse event counts by group and selected serious-event terms. It does not report a statistical analysis plan, primary analysis population, missing-data methods, or multiplicity approach. The non-randomized arms are not like-for-like controls, so their outcomes should not be interpreted as a randomized comparison.