This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec (NCT02014441), a na phase 2 study. The primary outcome is Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02014441 |
| Phase | Phase 2 |
| Condition | Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 61 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Participants with unresected, Stage IIIB to IVM1c melanoma were enrolled. The primary outcome population was narrower: participants who received at least one dose of talimogene laherparepvec and had at least one postdose blood or urine sample collected. The registry record reports enrollment of 61 participants, but it does not report the number who met the primary outcome population definition or the outcome denominator.
Intervention
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions. The recorded regimen began with a dose of 10⁶ plaque-forming units per mL, followed by 10⁸ plaque-forming units per mL 21 days after the initial dose and every 14 days thereafter.
Comparator
There was no concurrent comparator group. This was a single-group trial, with no allocation to different treatments and no masking. The outcome therefore describes detection among participants receiving talimogene laherparepvec; it is not a comparative estimate against another intervention or an untreated group.
Primary question
Among participants in the defined outcome population, what percentage had detectable talimogene laherparepvec DNA in blood or urine at any time during the first three cycles? DNA was measured using quantitative polymerase chain reaction. The registry record describes the outcome and its measurement schedule, but does not report the observed percentage or its confidence interval.
3. Trial Design
This was a Phase 2, multicenter, single-arm trial evaluating the biodistribution and shedding of talimogene laherparepvec in participants with unresected, Stage IIIB to IVM1c melanoma. The registry record lists 61 participants as enrolled and gives the status as completed. The recorded start date is 2014-04-07 and the primary completion date is 2016-01-25.
Participants received talimogene laherparepvec by injection into injectable cutaneous, subcutaneous, and nodal lesions. The recorded regimen began at 10⁶ plaque-forming units per mL, with a dose of 10⁸ plaque-forming units per mL 21 days after the initial dose and every 14 days thereafter. The arm description in the registry record is incomplete, so further treatment or follow-up details are not reported in the registry record.
Because the design had a single group and no allocation, it can describe whether drug DNA or virus was detected in sampled materials among treated participants. It cannot provide a randomized comparison of detection rates between treatment groups. The registry record lists secondary outcomes concerning clearance of DNA in blood and urine, detection of DNA or virus on the exterior of occlusive dressings, and detection of DNA or virus on the surface of injected lesions. These outcomes address different specimens and measurement targets, so they should not be treated as interchangeable measures.
The primary outcome population required receipt of at least one dose and at least one postdose blood or urine sample. Enrollment alone does not establish that every enrolled participant contributed to this analysis. The outcome denominator and the number of participants with a qualifying sample are not reported in the registry record. The record lists 35 outcome measures and no analysis records.
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.
Overall Study
| Stage | Talimogene Laherparepvec |
|---|---|
| STARTED | 61 |
| Received Treatment | 60 |
| COMPLETED | 49 |
| NOT COMPLETED | 12 |
Reasons for not completing this period:
| Reason | Talimogene Laherparepvec |
|---|---|
| Withdrawal by Subject | 12 |
Analysis population for the primary outcome, as defined in the registry: Participants who were enrolled, received at least 1 dose of talimogene laherparepvec, and had at least 1 postdose blood/urine sample collected.
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 (all participants who received at least 1 dose of talimogene laherparepvec)
| Characteristic | Unit | Talimogene Laherparepvec |
|---|---|---|
| Participants analysed | 60 | |
| Age, Continuous | years | 63.3 (SD 16.7) |
| Sex: Female, Male: Female | Participants | 27 |
| Sex: Female, Male: Male | Participants | 33 |
| Race/Ethnicity, Customized: White | Participants | 60 |
| Eastern Cooperative Oncology Group (ECOG) Performance: 0 (Fully active) | Participants | 45 |
| Eastern Cooperative Oncology Group (ECOG) Performance: 1 (Restrictive but ambulatory) | Participants | 15 |
| Herpes Simplex Virus Type 1 (HSV-1) Status: Negative | Participants | 17 |
| Herpes Simplex Virus Type 1 (HSV-1) Status: Positive | Participants | 40 |
| Herpes Simplex Virus Type 1 (HSV-1) Status: Unknown | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Detectable Talimogene Laherparepvec Deoxyribonucleic Acid (DNA) During the First Three Cycles, measured over Cycles 1 and 2 on days 1 (pre-dose and 1, 4, and 8 hours post-dose), 2, 3, 8, and 15 (cycle 1 only), cycle 3 on day 1 (pre-dose) and day 8, and cycle 4 on day 1 (pre-dose)..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with detectable talimogene laherparepvec DNA in blood or urine at any time during the first three cycles. The registry describes measurement by quantitative polymerase chain reaction and specifies a 95% confidence interval as the dispersion measure. The endpoint combines blood and urine detection into a participant-level outcome: a participant qualifies if DNA is detected in either specimen at any time in the stated period.
Detection is a measure of whether viral DNA was found in the sampled material under the assay and collection schedule. It is not, by itself, a measure of viable virus, infection, clinical benefit, or harm. The registry lists other outcomes that distinguish detection of DNA from detection of virus and that consider specimens from dressings or injected lesion surfaces. Those endpoints represent separate questions and should not be collapsed into the primary endpoint.
The collection schedule spans multiple visits in cycles 1 and 2, cycle 3, and a pre-dose visit in cycle 4. The endpoint description defines the primary period as cycles 1 to 3. The observed percentage, participant count, and confidence interval are not reported in the registry record. Without these results, the endpoint's estimated frequency and precision cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the question the trial was designed to address: how often talimogene laherparepvec DNA was detectable in blood or urine during the first three cycles among participants who received a dose and had a postdose sample. It does not report the primary endpoint result. Consequently, there is no reported participant count with detection, percentage, or confidence interval from which to describe the observed frequency or its precision.
The 61 enrolled participants are not automatically the denominator for the primary endpoint. The outcome population required both treatment exposure and at least one postdose blood or urine sample. The record does not give the number meeting those requirements, nor does it give the number with detectable DNA. The enrollment figure should therefore be read as a trial-level enrollment count, not as the reported denominator for the endpoint.
The design is single-arm, with no comparator. Any outcome estimate, if reported elsewhere, would describe observations within the treated group under the trial's sampling and assay procedures. It would not estimate a treatment effect relative to another group. The record also does not report a statistical analysis plan, an adjusted analysis, or analysis records. Thus, there is no registry-reported inferential analysis to interpret beyond the stated use of a 95% confidence interval for the primary outcome.
The endpoint is based on detection at any time in the specified period. Such a participant-level summary does not convey the timing, duration, or repeated pattern of detection. Those details would require results at the sample or visit level. The registry lists secondary outcomes on clearance and on DNA or virus detection in other specimen types, but their results are not reported in the registry record. A positive DNA assay and detection of virus are distinct endpoints in this record; findings for one should not be substituted for the other.
For these reasons, no conclusion about the magnitude of DNA detection or the uncertainty around that magnitude can be drawn from the registry results available in this record. The record supports description of the trial design, measurement approach, and planned outcome definition, but not a quantitative interpretation of the primary finding. Neither the absence of a reported estimate nor the single-arm design is evidence that detection did or did not occur.
9. Statistical Methods Explained
The statistical outcome is a participant-level percentage. Each participant in the defined analysis population is classified according to whether talimogene laherparepvec DNA was detected in blood or urine at any time during the first three cycles. The numerator would be participants meeting that detection definition, and the denominator would be participants in the endpoint population. The registry record does not report either count or the resulting percentage.
What does a percentage estimate?
For a binary outcome, a percentage expresses the share of the analyzed participants classified with the event. In this trial, the event is detectable DNA in blood or urine within the stated period. The estimate would be specific to the population that received a dose and contributed at least one postdose sample, as well as to the assay, specimens, and collection schedule used. It should not automatically be generalized to all enrolled participants or to settings with different sampling procedures.
The endpoint definition uses detection at any time, so the participant is counted according to whether a qualifying detection occurred during the period. This summary does not show how many samples were positive for that participant, how long detection persisted, or whether detection occurred in blood, urine, or both. Sample-level outcomes and participant-level outcomes answer different questions. The registry's secondary outcomes include percentages of samples and percentages of participants for some specimen types, reflecting that distinction.
What does the confidence interval communicate?
A confidence interval describes the statistical uncertainty around an estimated quantity under the method used to construct it. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. The registry identifies a 95% confidence interval for the primary endpoint, but the interval and the underlying estimate are not reported in the registry record. It is therefore not possible to judge the precision of this result or to compare the interval with any threshold.
A confidence interval does not correct for limitations in who contributed samples, how missing samples were handled, or how well the measured participants represent the population of interest. It also does not establish that a detected DNA signal represents infectious or viable virus. Those are questions of measurement, analysis population, and endpoint definition rather than interval width.
Why does the sampling schedule matter?
Detection depends partly on when specimens are collected. The listed schedule includes pre-dose and post-dose collections in cycles 1 and 2, additional collections during cycle 1, a pre-dose collection in cycle 3, and a pre-dose collection in cycle 4. The primary outcome description limits the detection summary to cycles 1 to 3. The schedule determines the opportunities to observe DNA; it cannot establish what happened between collections. The record does not provide detailed sampling compliance or the number of evaluable specimens at each time.
For repeated measurements, a participant may contribute multiple specimens, but the primary endpoint is described as a participant percentage rather than a sample percentage. Treating each specimen as an independent participant would not represent the stated endpoint, because repeated samples from one participant are related. The record does not report a model for repeated measurements, and the primary outcome's participant-level definition does not require such a model to describe the percentage.
What can a single-arm analysis establish?
A single-arm estimate can describe the observed outcome in that group. With no concurrent comparator, it cannot distinguish the treatment-associated pattern from differences that might have appeared under another intervention or no intervention. This is particularly important when interpreting a detection endpoint: a within-group proportion is not a comparative effect. No randomized contrast or treatment-effect estimate is reported in the registry record.
The record lists a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it states that the effect to detect is a stated fraction of the observed effect. Such figures are planning illustrations, not observed power and not results from this single-arm trial. They do not replace a trial-specific sample-size justification, which is not reported in the registry record. The registry record does not report a statistical plan explaining how that illustration relates to the trial's design.
How should recalculated results be understood?
No recalculated primary result is reported in the registry record. In general, a recalculation from posted summary statistics is an unadjusted calculation and may not reproduce a sponsor's analysis if the sponsor used different methods or analysis populations. The registry record does not provide a sponsor analysis or corresponding primary result for comparison, so no recalculation can be used to fill the reporting gap. The appropriate interpretation is that the result is not reported in the registry record, rather than that the outcome was absent or equal to a particular value.
The record reports no analysis records. This does not mean that no analyses were conducted; it means that no analysis records are listed in the registry information. In the absence of reported estimates, denominators, and analysis details, statistical interpretation should remain limited to the endpoint definition and design features that are documented.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 35 outcome measures, including the primary outcome and secondary outcomes involving clearance and detection in blood, urine, dressings, and injected lesion surfaces. It does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for testing multiple outcomes. The record also lists no analysis records. It is therefore not possible to determine which outcomes were included in formal statistical testing, whether any testing was prespecified, or how multiplicity was handled.
Multiplicity matters when many statistical questions are assessed: interpreting each result as if it were the only analysis can make chance findings more likely across the collection of tests. This is a general statistical concern, not evidence that a particular finding in this trial is spurious. With no outcome estimates or analysis records reported, there is no basis to assess the consequences of multiplicity for this trial's findings.
The primary outcome population required participants to have received at least one dose and to have at least one postdose blood or urine sample. The record does not state how missing samples were handled, whether participants with incomplete sampling were excluded, or whether any imputation was used. It does not report the endpoint denominator or reasons for missing samples. These omissions limit assessment of whether the observed population could differ from the enrolled group in ways that affect the endpoint.
The analysis population is defined by the outcome description, but the record does not provide a fuller statistical analysis plan or explain how protocol deviations were treated. The enrollment count should not be substituted for the unreported endpoint denominator. No assumptions about missingness or participant inclusion can be verified from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Talimogene Laherparepvec | 13 | 60 | 21.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Talimogene Laherparepvec | 58 of 60 |
Most frequent serious adverse event terms
| Event term | Organ system | Talimogene Laherparepvec |
|---|---|---|
| Delirium | Psychiatric disorders | 2 of 60 |
| Pyrexia | General disorders | 2 of 60 |
| Atrial fibrillation | Cardiac disorders | 1 of 60 |
| Cardiac failure congestive | Cardiac disorders | 1 of 60 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 60 |
| Cholelithiasis | Hepatobiliary disorders | 1 of 60 |
| Cellulitis | Infections and infestations | 1 of 60 |
| Pneumonia | Infections and infestations | 1 of 60 |
| Sepsis | Infections and infestations | 1 of 60 |
| Skin infection | Infections and infestations | 1 of 60 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Talimogene Laherparepvec |
|---|---|---|
| Chills | General disorders | 39 of 60 |
| Fatigue | General disorders | 34 of 60 |
| Nausea | Gastrointestinal disorders | 27 of 60 |
| Headache | Nervous system disorders | 27 of 60 |
| Pyrexia | General disorders | 23 of 60 |
| Vomiting | Gastrointestinal disorders | 15 of 60 |
| Injection site pain | General disorders | 15 of 60 |
| Pain | General disorders | 15 of 60 |
| Diarrhoea | Gastrointestinal disorders | 13 of 60 |
| Myalgia | Musculoskeletal and connective tissue disorders | 12 of 60 |
Serious events with the highest arm-level rate: delirium (3.3%), pyrexia (3.3%), atrial fibrillation (1.7%), cardiac failure congestive (1.7%), abdominal pain upper (1.7%).
The registry safety figures list 60 participants at risk for serious adverse events, with 13 affected. For other adverse events, the record lists 60 at risk and 58 affected. These are separate categories in the safety record; the figures should not be added or treated as interchangeable. Enrollment was 61, but the safety group at-risk count is 60, so the enrollment count is not the safety denominator.
The listed leading serious adverse event terms and percentages are delirium, 3.3%; pyrexia, 3.3%; atrial fibrillation, 1.7%; cardiac failure congestive, 1.7%; abdominal pain upper, 1.7%; and cholelithiasis, 1.7%. These entries describe reported terms and their listed percentages. They do not establish that talimogene laherparepvec caused an event, and the record does not provide enough detail to assess timing, severity within each term, or clinical context.
Safety counts in a single-arm trial describe events recorded among participants in that group. Without a comparator, they do not estimate an excess risk attributable to treatment. The registry record lists no deaths for the safety group, but does not provide a fuller safety narrative or an explanation of event attribution. These figures should be read as registry-reported counts and terms, not as a complete account of safety or a basis for individual medical decisions.
12. What the Result Does, and Does Not, Mean
The trial's primary question concerns detection of talimogene laherparepvec DNA in blood or urine after administration, within the first three cycles. The registry record describes the population, assay, endpoint, and sampling schedule. It also documents secondary outcomes addressing clearance and detection in additional specimens. This information clarifies what the investigators intended to measure and how the primary outcome was defined.
The record does not report the primary outcome estimate, numerator, denominator, or confidence interval. It therefore does not establish how often DNA was detected in the defined population, nor how precisely that frequency was estimated. The missing result should not be interpreted as zero detection or as evidence that no samples were positive. It is a reporting limitation in the registry record.
Even if a participant-level detection percentage were available, its meaning would be bounded by the endpoint. Detection of DNA by quantitative polymerase chain reaction is not the same as detection of virus, and neither measurement alone establishes a clinical outcome. The separate outcomes for DNA and virus, and for blood, urine, dressings, and lesion surfaces, answer distinct questions. A result for one specimen or analyte would not automatically answer the others.
The single-arm design also limits interpretation. A within-group description can characterize observations among treated participants but cannot show what would have occurred in a comparable group receiving another intervention or no treatment. The registry results do not report a treatment comparison. The study's results therefore cannot be interpreted as a comparative estimate of benefit or harm on the basis of this record.
In short, the record supports a clear description of the trial's measurement objective and design, but not a quantitative conclusion about its primary finding. It does not provide the outcome details needed to assess the observed detection frequency, precision, or missing-data impact. No medical recommendation follows from the design information alone.
13. Why This Trial Matters Statistically
This trial raises an important statistical distinction between detecting a biological marker and establishing a clinical effect. Its primary endpoint is a participant-level percentage based on DNA detection in blood or urine, while the listed secondary outcomes distinguish DNA from virus and participant-level outcomes from sample-level outcomes. Keeping these measures separate is essential: each represents a different measurement target and denominator.
The endpoint also illustrates how a sampling schedule shapes what can be observed. A finding of detectable DNA at any time during the stated period depends on the specimens collected and the assay used. A summary over participants does not describe the pattern across samples or the time between detection and clearance. The registry lists clearance outcomes, but does not report their results. The outcome definitions alone cannot establish the temporal course of detection.
The single-arm design makes the interpretation boundary especially clear. The study can be understood as describing detection after administration in its enrolled group; it does not provide a concurrent comparison for estimating differences between groups. Statistical precision for a within-group percentage, even if available, would not resolve the absence of a comparator.
Finally, the registry record separates trial conduct information from reported results. It gives enrollment and design details, but not the primary estimate or confidence interval, and lists 35 outcome measures with no analysis records. This makes transparent reporting of denominators, missing samples, outcome estimates, and analysis methods particularly relevant. Without those items, readers can understand the question but cannot assess the numerical answer or its uncertainty.
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 reporting gaps limit interpretation. The primary percentage, its numerator and denominator, and its 95% confidence interval are not reported in the registry record. Although enrollment is reported as 61, the endpoint population required a postdose blood or urine sample, and its size is not reported. The number of participants with a qualifying DNA detection is also not reported.
The registry describes a sampling schedule but does not report the number of collected or evaluable specimens at each visit, adherence to the schedule, or how missing samples were handled. The primary endpoint is defined as detection at any time, but the record does not provide results by visit or specimen. It is not possible to assess whether incomplete sampling affected the estimated percentage.
The record lists many outcomes but does not report a multiplicity approach or an analysis plan. It does not provide enough information to evaluate prespecification, analysis populations beyond the primary outcome definition, handling of protocol deviations, or any adjustment. No analysis records are listed. These omissions prevent review of the statistical methods used for reported outcomes.
The single-arm design supplies no concurrent control group, limiting causal or comparative interpretation. The arm description is incomplete, and additional treatment or follow-up details are not reported in the registry record. The assay's detection threshold and fuller information about its performance are not reported in the registry record. The posted information therefore supports description of the intended measurement, but leaves important questions about implementation and analysis unresolved.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Single-arm Trial to Evaluate the Biodistribution and Shedding of Talimogene Laherparepvec — NCT02014441.
- Registry record last updated 2019-11-20; status last verified 2019-11.
- Results first posted 2017-02-14.
- 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.
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18. Record Summary
NCT02014441 is a completed Phase 2, multicenter, single-arm trial of talimogene laherparepvec in participants with unresected, Stage IIIB to IVM1c melanoma. The registry lists 61 enrolled participants, no allocation, and no masking. The recorded start date is 2014-04-07, and the primary completion date is 2016-01-25.
The primary outcome was the percentage of participants with detectable talimogene laherparepvec DNA in blood or urine during the first three cycles, measured using quantitative polymerase chain reaction. The endpoint population required at least one dose and at least one postdose sample. The primary result, denominator, and confidence interval are not reported in the registry record.
The record lists 35 outcome measures and no analysis records. Safety information lists 13 of 60 participants affected by serious adverse events and 58 of 60 affected by other adverse events. The single-arm design supports description of outcomes within the treated group, not a randomized comparison.