Tecemotide (L-BLP25) in Rectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tecemotide (L-BLP25) in Rectal Cancer (NCT01507103), a randomized phase 2 study. The primary outcome is Change From Baseline in Tumor Immune Response Evaluated by Immunohistochemical (IHC) Analysis of Tumor Infiltrating Lymphocytes (TILs) at Week 14 (Post-surgery).

2. Clinical Question

The registry describes the study as a mechanistic trial. Its stated objective was to assess the effect of tecemotide on the MUC1-specific immune response in people with newly diagnosed rectal cancer eligible for neoadjuvant therapy. The biological rationale in the record is that tecemotide was designed to induce an immune response against tumor tissue expressing MUC1, and the study considered whether treatment might be associated with tumor-specific immune activity and tumor-infiltrating lymphocytes.

The primary endpoint focused on a tissue-based measure after surgery rather than a clinical outcome such as survival or tumor recurrence. The registry also lists changes in peritumoral immune response at Week 14 and immunological response in peripheral blood at Week 18 as secondary outcomes. Numerical results for these outcomes are not reported in the registry record. The available record therefore identifies the biological question and measurement approach, but does not establish the size or direction of any treatment-group differences.

3. Trial Design

This was a phase 2, randomized, open-label, parallel-group study. The registry lists an enrollment of 124 and describes the study as completed. The study began in 2012-02, with primary completion in 2014-06. Merck KGaA, Darmstadt, Germany, is listed as the sponsor.

The three treatment groups were chemoradiotherapy alone, chemoradiotherapy with tecemotide (L-BLP25), and chemoradiotherapy with tecemotide plus CPA. The registry identifies random allocation and no masking. It does not report the randomization method, allocation ratio, concealment procedures, or a detailed schedule of treatment administration in the registry record for this account. The arm descriptions themselves contain no additional details.

Because the study was open-label, participants and study personnel were not masked to treatment assignment according to the registry’s masking classification. The primary outcome was change from baseline in tumor immune response assessed by immunohistochemical analysis of tumor-infiltrating lymphocytes at Week 14 after surgery. The listed measure was the mean number of TILs per 100 tumor cells. Secondary outcomes addressed peritumoral immune response at Week 14 and peripheral-blood immunological response at Week 18.

The primary-outcome analysis population was defined by availability of baseline ELISpot blood and tumor samples, a tumor sample at surgery, and a pre-surgery ELISpot blood draw, as well as a MUC1-positive baseline tumor biopsy. The record does not state how many randomized subjects met those criteria or how many contributed to each outcome analysis. It also does not report the planned sample-size justification, the allocation procedure, or a detailed statistical analysis plan. The record identifies the trial’s design and endpoints, but these omissions limit assessment of how the study was planned and how the analyzed population related to the enrolled population.

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: Enrolled: 140 screened for eligibility; 16 excluded (mainly due to non-fulfillment of inclusion or exclusion criteria), 124 subjects randomized.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Immunomonitoring analysis set included all subjects for whom at least the baseline ELISpot blood and tumor sample, tumor sample at surgery and pre-surgery ELISpot blood drawing are available and whose tumor biopsy at baseline is MUC1-positive. Within the data table, n=number of subjects analyzed for each category.

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: Safety analysis set included all subjects who received at least one dose of study treatment (tecemotide \[L-BLP25\] or CPA).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Tumor Immune Response Evaluated by Immunohistochemical (IHC) Analysis of Tumor Infiltrating Lymphocytes (TILs) at Week 14 (Post-surgery), measured over Baseline and Week 14 (post-surgery).

The primary endpoint measured change in tumor-infiltrating lymphocytes between baseline and Week 14 after surgery. TILs are immune cells present in or around tumor tissue. For this endpoint, the registry expresses the measure as the number of TILs per 100 tumor cells, using immunohistochemical analysis of tumor biopsy samples.

According to the registry, samples were collected before baseline and after surgery. TILs were evaluated in three of the most abundant high-power fields at x40 for each sample; the mean was used after excluding the lowest and highest value. The endpoint was described as a mean of a continuous measure, with standard deviation as the dispersion measure. The outcome therefore represents a quantitative tissue-based measure rather than a simple yes-or-no response.

A change-from-baseline endpoint aims to describe how the measured immune-cell level differs between a starting assessment and a later assessment. In this study, that change was intended to characterize tumor immune response after treatment and surgery. It does not, on its own, measure a clinical benefit or establish that any observed immune change was caused by a specific treatment. Interpreting it would require the actual group-level changes, their uncertainty, and the analysis used to compare groups. Those numerical primary-outcome results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a continuous outcome: the number of tumor-infiltrating lymphocytes per 100 tumor cells. The registry specifies a mean as the summary parameter and standard deviation as the measure of dispersion. A mean describes the average measured value in an analyzed group; a standard deviation describes how spread out individual observations are around that average. Neither statistic is reported numerically for the primary outcome in the registry record.

What does a change-from-baseline measure represent?

In general, a change-from-baseline outcome compares a participant’s later measurement with that participant’s starting measurement. It can focus attention on within-person movement over time, while a comparison across randomized groups asks whether those changes differ between treatment strategies. The meaning of a group contrast depends on how the change was calculated and modeled. The registry identifies the outcome as change from baseline, but the detailed model and comparison method are not reported in the registry record.

In this trial, baseline and post-surgery tissue samples were assessed using immunohistochemistry. The registry says that TILs were evaluated in three of the most abundant high-power fields at x40 for each sample, and that the mean was considered after excluding the lowest and highest value. That describes a field-selection and summarization procedure for the tissue measurement. It does not provide information about reader blinding, reproducibility between readers, or procedures for resolving disagreement; those details are not reported in the registry record.

Why do uncertainty estimates matter?

General statistical explanation: an estimate is a summary of the observed data, while a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrow interval generally indicates greater precision than a wide interval, but precision is not the same as clinical importance. A p-value, when reported, addresses compatibility between data and a specified statistical model or null hypothesis; it does not state the probability that a treatment works. The registry entries available for this account do not report primary-outcome confidence intervals or p-values, so the precision and statistical evidence for the endpoint cannot be assessed.

The registry describes the endpoint as a mean with standard deviation, but a mean alone would not show the full distribution of TIL measurements. General statistical explanation: when observations are highly skewed or include influential values, the mean and standard deviation can be sensitive to those features. The distributional shape and diagnostic checks are not reported in the registry record. These considerations do not establish that the measure was skewed; they explain why the distribution and analytic assumptions are relevant when interpreting continuous data.

What does randomization contribute?

General statistical explanation: random assignment is intended to make treatment groups comparable, on average, with respect to measured and unmeasured baseline characteristics. It supports causal interpretation of a well-conducted comparison, but does not guarantee balance in a particular trial or address bias from missing outcomes, deviations from assigned treatment, or measurement procedures. The record identifies the study as randomized, but the randomization method and allocation concealment are not reported in the registry record.

Open-label status means treatment assignment was not masked, according to the registry. For an outcome involving tissue assessment, masking of those assessing samples could be relevant to measurement bias. Whether assessors were masked is not reported in the registry record. This is a question about the conduct and measurement of the trial, not evidence that bias occurred.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make standard errors too small if ignored, which can in turn make confidence intervals too narrow and tests appear more decisive than warranted. The primary endpoint is described as a continuous mean, but the registry entries do not report the model, distributional diagnostics, or whether over-dispersion was assessed. It should therefore be treated as a general consideration, not a finding about this trial.

The registry entries describe sample-size illustrations based on fractions of the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are planning illustrations rather than observed power. Numerical illustration results are not reported in the registry record details available for this account. The trial’s own sample-size justification and assumptions are also not reported in the registry record. No conclusion about the design’s ability to detect an effect should be drawn from the enrollment figure alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including a primary tissue-based immune measure and secondary immune measures at different times. It also identifies multiple treatment groups. When several outcomes, time points, or group comparisons are examined, the chance of obtaining at least one apparently notable result can increase unless the analysis accounts for multiplicity. General statistical explanation: multiplicity procedures can control error rates across a defined family of tests, but their appropriateness depends on which comparisons were planned and how they were prioritized.

The registry record does not report a multiplicity-adjustment procedure, a hierarchy of tests, or which pairwise comparisons were planned. It also does not report the detailed statistical analysis plan. Because the primary outcome has several categories or time points, it is not reduced to a single comparison in the available results. Numerical outcome results and comparison-specific estimates are not reported in the registry record, so it is not possible to assess the impact of multiple testing on interpretation.

The primary analysis population required baseline ELISpot blood and tumor samples, a tumor sample at surgery, a pre-surgery ELISpot blood draw, and a MUC1-positive baseline biopsy. The number of subjects meeting those criteria, the number with missing measurements, and the handling of missing data are not reported in the registry record. General statistical explanation: missingness can affect estimates when the probability of an unavailable measurement is related to treatment, health status, or the unobserved outcome. The direction and size of any such effect cannot be determined without information about missingness patterns and analytic handling.

The record does not state whether the primary analysis followed randomized assignment regardless of treatment received, used a per-protocol population, or applied another approach. It also does not provide an account of exclusions or withdrawals by group. Consequently, the relationship between the randomized population and the analyzed population cannot be fully evaluated.

11. Safety Results

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

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: gastrointestinal stoma complication (5.1%), dehydration (4.9%), gastrointestinal necrosis (2.6%), ileus (2.6%), intestinal obstruction (2.6%).

The registry reports, for each treatment group, the number at risk and the number affected for serious adverse events and for other adverse events. These are event summaries, not treatment-effect estimates. The record lists 39 at risk and 10 affected for serious adverse events in the chemoradiotherapy, tecemotide, and CPA group; 41 at risk and 10 affected in the chemoradiotherapy and tecemotide group; and 42 at risk and 12 affected in the chemoradiotherapy group. For other adverse events, the corresponding figures are 39 and 38, 41 and 41, and 42 and 41.

The registry also lists serious-event terms with percentages: Gastrointestinal stoma complication, 5.1%; Dehydration, 4.9%; Gastrointestinal necrosis, 2.6%; Ileus, 2.6%; Intestinal obstruction, 2.6%; and Peritoneal haemorrhage, 2.6%. These terms are not linked to a particular group in the registry record for this account, and their denominators are not stated. They should not be used to infer group-specific risks or to compare treatments.

Death counts are null in the record, meaning they are not reported in the registry record; null does not mean zero. The registry entries do not describe adverse-event definitions, severity grading, exposure time, or attribution procedures. Differences in counts alone do not establish causation, and these summaries do not provide a complete safety assessment.

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

This trial’s central statistical question was whether tumor-infiltrating lymphocytes changed from baseline to Week 14 after surgery across treatment groups. The record establishes that the study was randomized, open-label, and organized into three parallel groups. It also specifies a tissue-based immune measure and a restricted analysis population. These details show what the trial was designed to examine, but they are not outcome findings.

Numerical results for the primary endpoint are not reported in the registry record. Without group-level estimates and their uncertainty, the observed direction and magnitude of TIL change cannot be described. Nor can the evidence for differences between treatment groups be assessed. The same limitation applies to the listed secondary immune outcomes. An endpoint title or biological rationale is not a substitute for observed results.

Even if a change in TILs were reported, the endpoint would remain a measure of immune activity in tumor tissue. By itself, it would not show that patients lived longer, had fewer recurrences, or experienced improved symptoms. The registry information in this account does not establish a relationship between the immune measure and those clinical outcomes.

The adverse-event summaries describe counts of affected subjects and selected serious-event terms, but do not provide all the information needed for treatment comparisons. The event terms are not attributed to specific groups in the registry entries, and the death counts are not reported. These data should therefore be read descriptively rather than as definitive evidence for or against a safety difference.

In short, the record permits a careful account of the trial question, design, endpoint construction, and some safety summaries. It does not permit a conclusion about whether the treatment groups differed in immune response or about the clinical importance of any such difference. This distinction between a mechanistic measurement and a patient-centered clinical outcome is important when interpreting the study’s scope.

13. Why This Trial Matters Statistically

This trial is statistically notable for asking a mechanistic question within a randomized clinical design. Its primary endpoint was a tissue-based immune measure, TILs per 100 tumor cells, assessed from biopsy samples at baseline and after surgery. That focus differs from a direct comparison of clinical outcomes. It makes the measurement process, the timing of sample collection, and the definition of the analysis population central to interpretation.

The three parallel groups also raise questions about how treatment contrasts were prioritized. The registry identifies chemoradiotherapy alone, chemoradiotherapy with tecemotide, and chemoradiotherapy with tecemotide plus CPA. A complete interpretation would need estimates for the prespecified comparisons and a clear account of how multiple comparisons were handled. Those details, including the statistical analysis plan, are not reported in the registry record.

The eligibility criteria for the primary analysis illustrate an important distinction between enrollment and endpoint availability. The outcome population required multiple samples and a MUC1-positive baseline biopsy. This could be relevant to how broadly an outcome estimate applies, but the number meeting the criteria and the handling of missing samples are not reported in the registry record.

The study also shows why a biological outcome should be interpreted alongside its uncertainty and limitations. A mean change can summarize a continuous measure, but without estimates, variability, and a comparison method, it cannot establish the size or precision of a group difference. The numerical primary and secondary results are not reported in the registry record. As a result, the statistical importance of the trial lies in its clearly defined mechanistic question and the interpretive issues its design raises, rather than in a numerical treatment-effect conclusion available from these registry entries.

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 most important limitation for interpreting the posted record is that numerical primary-outcome results are not reported in the registry record. The same applies to the listed secondary immune outcomes. Without estimates, measures of uncertainty, and comparison results, no account of the observed immune-response pattern or its precision is possible.

The primary analysis population depended on sample availability and MUC1-positive baseline tumor status. The number meeting these criteria is not reported in the registry record, nor are the number of missing measurements, reasons for missingness, or methods used to handle missing data. This makes it difficult to assess how the analyzed population relates to those enrolled.

The registry classifies the study as open-label. It does not report whether tissue assessors were masked to treatment assignment, or whether measurement reliability was evaluated. These omissions matter for an endpoint based on immunohistochemical assessment, although they do not establish that measurement bias occurred.

The detailed statistical analysis plan is not reported in the registry record. In particular, the randomization procedure, planned group contrasts, multiplicity approach, model assumptions, and treatment of protocol deviations are not specified in the registry record for this account. The trial’s sample-size justification is also not reported. The record includes descriptions of planning illustrations, but numerical planning estimates are not reported in the registry record details.

Safety interpretation is limited because the serious-event terms are not assigned to treatment groups, their denominators are not stated, and death counts are not reported. These constraints prevent a comprehensive comparison of safety profiles from the listed summaries alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Tecemotide (L-BLP25) in Rectal Cancer — NCT01507103.
• Registry record last updated 2017-01-13; status last verified 2017-01.
• Results first posted 2016-06-02.
• 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

The registry describes NCT01507103, Tecemotide (L-BLP25) in Rectal Cancer, as a completed phase 2 randomized, open-label, parallel-group trial sponsored by Merck KGaA, Darmstadt, Germany. The listed enrollment is 124. The study began in 2012-02 and had primary completion in 2014-06.

Three treatment groups were listed: chemoradiotherapy alone, chemoradiotherapy with tecemotide, and chemoradiotherapy with tecemotide plus CPA. The primary outcome was change from baseline in tumor-infiltrating lymphocytes per 100 tumor cells at Week 14 after surgery. Secondary outcomes concerned peritumoral immune response at Week 14 and peripheral-blood immunological response at Week 18.

The primary analysis population required specified blood and tumor samples and a MUC1-positive baseline biopsy. Numerical primary and secondary outcome results, detailed analysis methods, and the handling of missing data are not reported in the registry record. Safety summaries include affected counts and selected serious-event terms, but the listed terms are not assigned to treatment groups in the registry entries.