Messenger RNA (mRNA)-Based, Personalized Cancer Vaccine Against Neoantigens Expressed by the Autologous Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Messenger RNA (mRNA)-Based, Personalized Cancer Vaccine Against Neoantigens Expressed by the Autologous Cancer (NCT03480152), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants Who Had a Clinical Response (Complete Response + Partial Response) to Treatment (Objective Tumor Regression).

2. Clinical Question

3. Trial Design

This was a Phase I/II study of an mRNA-based personalized cancer vaccine, sponsored by the National Cancer Institute (NCI). The registry describes the allocation as nonrandomized, the masking as none, and the model as sequential. Enrollment was 5. The record lists metastatic melanoma and epithelial cancer in its study description, and names several cancer conditions in its condition list.

The design descriptions distinguish a phase I dose-escalation approach from a phase II arm using the maximum tolerated dose established in phase I. The record does not report a randomized allocation process, blinded assessment, or a concurrent control arm. Accordingly, the trial does not support a like-for-like randomized comparison between treatment and control groups. Differences between participants or stages could not be interpreted as randomized treatment effects.

The study began on 2018-05-18, had a primary completion date of 2019-06-25, and is listed as terminated. The reason for termination is not reported in the registry record. The brief description says vaccine injections were planned every 2 weeks for up to 8 weeks, and that participants might receive a second course if the study doctor determined it was needed. The primary response endpoint had a timeframe of up to 12 months.

The registry lists 6 outcome measures, but the details and results for all of them are not available in the record summarized for this trial. One secondary outcome is identified as the number of participants with an increase in the quantity and quality of circulating antigen-specific T cells. No statistical analysis is listed. The record does not report the protocol’s statistical plan, sample-size justification, analysis populations, or interim-analysis procedures.

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: Two step registration process. Step One: Patient signed consent to create vaccine. Step Two: Once vaccine is available, patient screened for eligibility criteria. If eligibility criteria were met, registration and enrollment was completed and the patient was treated. One patient died between Step one and Step two and was not treated.

Phase I

Reasons for not completing this period:

Phase II

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: No baseline data was collected for the participant that signed consent for vaccine but died before treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Had a Clinical Response (Complete Response + Partial Response) to Treatment (Objective Tumor Regression), measured over up to 12 months.

The primary endpoint is the number of participants who had a clinical response, defined as complete response plus partial response, assessed by RECIST v1.1 up to 12 months. It is a count of participants, not a time-to-event outcome or a measure of change in a laboratory marker. The endpoint groups complete and partial tumor regression into a clinical-response category.

Under the registry’s RECIST description, complete response means disappearance of all target lesions, with pathological lymph nodes reduced to a short axis of < 10 mm. Partial response means at least a 30% decrease in the sum of the diameters of target lesions relative to the baseline sum. The same description defines stable disease as neither sufficient shrinkage for partial response nor sufficient increase for progressive disease. Progressive disease includes a relative increase of at least 20% together with an absolute increase of at least 5 mm, or the appearance of new lesions.

Objective response criteria provide a structured way to classify tumor changes using defined imaging rules. Combining complete and partial response gives a count of participants meeting either response category during the stated timeframe. This can describe observed tumor regression in the study population, but by itself does not establish that the vaccine caused the responses. The record does not report the number meeting the endpoint, the number assessed, or the handling of participants without an evaluable assessment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint?

The primary endpoint is a count of participants classified as having complete or partial response. The registry identifies the measure as a count of participants, and the endpoint combines two RECIST v1.1 categories. It is therefore a binary participant-level classification for the purpose of counting: each assessed participant either meets the stated response definition or does not. The underlying registry description also names stable disease and progressive disease, but does not give their observed counts.

General statistical explanation: for a binary outcome, a study can report the number of participants meeting the definition and, when the denominator is known, a proportion. A count alone does not provide the proportion unless the relevant denominator is also reported. Neither the response count nor the endpoint denominator is reported in this registry record. No response estimate can be reconstructed from the enrollment count.

What does RECIST contribute?

RECIST v1.1 supplies standardized criteria for categorizing changes in target lesions and lymph nodes. The registry defines complete response as disappearance of all target lesions, with pathological lymph nodes reduced to a short axis of < 10 mm. It defines partial response by at least a 30% reduction in the sum of target-lesion diameters from baseline. It also describes stable disease and progressive disease, including the relative and absolute increase criteria and the appearance of new lesions.

General statistical explanation: prespecified classification rules can improve consistency by making the endpoint less dependent on an informal judgment of whether a tumor has improved. Their usefulness still depends on complete and consistently conducted assessments. The registry does not report details about who assessed scans, whether assessments were independently reviewed, how missing scans were handled, or how borderline findings were adjudicated.

What can be inferred from the design?

The trial is described as nonrandomized and sequential, with no masking. Its phase I arm descriptions refer to escalating doses, while the phase II description refers to the maximum tolerated dose established in phase I. This supports describing the study as a dose-development study with successive stages. It does not support treating the arms as randomized comparison groups.

General statistical explanation: randomization is used to make treatment groups comparable, on average, with respect to both measured and unmeasured participant characteristics. Without randomization, observed differences between groups can reflect factors other than treatment. Masking can reduce some forms of assessment or reporting influence, but none is listed for this trial. These considerations are relevant when interpreting any between-group comparison; the registry does not report an analysis comparing the arms.

What does the analysis information show?

The registry lists 6 outcome measures and 0 analyses. It identifies a primary clinical-response endpoint and one secondary immune-response outcome in the available information. A statistical analysis, effect estimate, uncertainty interval, and significance test are not reported. The analysis populations, treatment of missing data, and methods for handling multiple outcomes are also not reported in the registry record.

General statistical explanation: an analysis plan ordinarily specifies how outcomes will be summarized, which participants will be included, and how uncertainty will be quantified. A confidence interval can communicate the range of estimates compatible with the data under a stated model; a p-value can summarize how unusual the observed data would be under a specified null hypothesis and assumptions. Neither measure alone establishes clinical importance or causation. No such quantities are reported for the primary endpoint.

How should the planning assumptions be read?

The record describes 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 describes the target effect as a stated fraction of the observed effect. These are assumptions for a planning calculation, not results from the trial and not evidence of observed power. The calculation outputs are not reported in the registry information available for this trial.

There is an important design distinction: the planning illustration assumes equal allocation between two arms, whereas the study itself is described as nonrandomized and sequential, with dose-escalation and phase-specific arms. The illustration should not be mistaken for the trial’s own design or statistical plan. The protocol’s sample-size justification and its intended analysis methods are not reported in the registry record.

General statistical explanation: a planning calculation depends on choices about the target effect, significance level, allocation, and statistical approximation. Its result is conditional on those assumptions. A planning calculation does not demonstrate that a trial could reliably detect an effect, and a post hoc calculation based on an observed effect does not change the uncertainty in the observed result. For this trial, no primary response estimate is reported, so the planning illustration cannot provide a substitute for an outcome analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures, but the available record identifies only the primary clinical-response endpoint and one secondary outcome concerning an increase in the quantity and quality of circulating antigen-specific T cells. The remaining outcome definitions and their results are not reported in the registry record. It lists 0 analyses, so no analysis results or multiplicity procedures are available to review.

General statistical explanation: when a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently notable result can increase if each is assessed separately. A statistical plan may specify a primary endpoint, a testing sequence, or an adjustment method to address this issue. The registry record does not report whether such a plan was prespecified or whether any adjustment was used. No adjustment should be inferred from the list of outcomes alone.

Missing-data methods and analysis populations are also not reported in the registry record. In particular, the record does not state how many participants had an evaluable tumor assessment, whether participants who discontinued were included in the primary endpoint, or how unavailable assessments were classified. The enrollment count of 5 cannot be assumed to be the endpoint denominator.

General statistical explanation: missing outcome information can affect both the estimate and its precision, especially when the number of participants is small. The direction of any resulting bias depends on why data are missing and on the analysis method. Without the participant flow, endpoint denominator, and missing-data rules, the impact cannot be assessed for this trial.

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 non-serious adverse event terms

The registry’s serious adverse-event figures are reported separately for two phase I dose-level groups. For the group titled Dose Level 2 - 0.13mg, 2 participants were listed as at risk for serious adverse events and 0 as affected. For the group titled Dose Level 3 - 0.39mg, 2 were listed as at risk and 0 as affected. The registry lists 0 deaths for each group. No serious adverse-event terms are listed in the record.

The separately listed other adverse-event figures show 2 at risk and 2 affected in each of those dose-level groups. These figures are not the serious adverse-event counts and should not be read as counts of serious events. The registry does not provide event terms for these other adverse events in the information.

These are small group-level counts, not a comparative safety estimate. The study was nonrandomized and sequential, and the record does not provide a randomized control group or a like-for-like comparison. It also does not report the duration of safety observation for each participant, the event definitions beyond the serious-versus-other grouping, or whether participants could contribute to more than one group. The figures therefore describe what is listed in the registry, but do not establish comparative safety or rule out events not captured in the reported record.

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

The registry record gives a clear primary endpoint definition: the number of participants with complete or partial response under RECIST v1.1, assessed up to 12 months. It also describes the study as a Phase I/II, nonrandomized, sequential evaluation of a personalized mRNA vaccine, with escalating doses in phase I and a phase II arm using a maximum tolerated dose established in phase I.

What the record does not provide is the primary response count, the endpoint denominator, a response proportion, or an estimate of uncertainty. It does not report a statistical analysis, a p-value, or a confidence interval. Consequently, the registry information cannot show how many participants met the response definition or how precisely any response estimate was measured.

The lack of a randomized comparator also limits causal interpretation. Even if outcome differences between stages or dose groups were reported, this design would not by itself establish that the vaccine caused those differences. Participant characteristics, disease course, dose stage, and other factors could contribute. In this record, no arm comparison or clinical-response result is reported.

General statistical explanation: a study’s endpoint definition tells readers what was measured, while its results show what was observed. A defined endpoint without reported results cannot answer whether the outcome occurred or how often. Likewise, a small enrollment count does not determine the result, the endpoint denominator, or the precision of an estimate.

The record’s terminated status is a factual status, not an explanation of the study’s findings or why it ended. The reason for termination and the completeness of follow-up are not reported in the registry record. The defensible interpretation is therefore limited to the trial’s stated objective, design, endpoint definitions, and listed safety counts; efficacy results and a treatment-effect conclusion cannot be drawn from the information reported.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a detailed outcome definition and an interpretable outcome result. The registry describes an objective tumor-response endpoint using RECIST v1.1, including explicit criteria for complete response, partial response, stable disease, and progressive disease. These rules make the intended classification understandable, but the absence of a reported response count and denominator prevents readers from estimating how often the primary outcome occurred.

It also shows why design information matters in early-phase research. The study is nonrandomized and sequential, with dose escalation and a later phase II arm based on the maximum tolerated dose established in phase I. Those features describe a dose-development approach, not a randomized comparison. The design can be described accurately without implying that differences between stages would isolate a treatment effect.

The enrollment count of 5 underscores the importance of reporting participant flow, endpoint denominators, and uncertainty. General statistical explanation: in a small study, individual outcomes can have a substantial effect on a summary estimate, and interval estimates can be important for communicating precision. The registry does not report an interval or the number assessed for the primary endpoint, so neither the estimate nor its precision can be evaluated from this record.

Finally, the record lists multiple outcome measures but no analyses. That makes it impossible to assess how outcomes were prioritized, whether multiplicity was addressed, or how missing information was handled. Clear reporting of these elements is central to distinguishing what a trial set out to measure from what its data can support. Here, the registry record supports a statistical reading of the design and measurement framework, but not a numerical conclusion about clinical response.

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 main trial-specific limitation for statistical interpretation is the absence of reported primary outcome results. Although the registry defines clinical response and gives a timeframe of up to 12 months, it does not report the response count, endpoint denominator, or participant-level outcome categories. The record therefore cannot support an estimate of response frequency or its precision.

Enrollment was 5, but the registry does not describe participant characteristics, cancer-type distribution, dose exposure, discontinuations, or evaluable follow-up. It is not possible to determine from the record whether all enrolled participants contributed to the primary endpoint. The reason for the terminated status and its relationship, if any, to follow-up or data completeness are not reported.

The nonrandomized, sequential design and absence of masking limit the interpretation of any potential differences across stages or dose levels. The registry does not identify a like-for-like randomized comparator, and it reports no arm-level clinical-response results. Consequently, the record does not permit a comparative estimate or a causal attribution to treatment.

The registry lists 6 outcome measures and 0 analyses. Details of the other outcomes, the statistical analysis plan, the analysis populations, missing-data handling, multiplicity procedures, and interim analyses are not reported in the registry record. The planning illustration’s assumptions do not fill these gaps or constitute the trial’s own design justification. The safety information is also limited to group-level counts; event terms are not listed for serious events, and the record does not provide fuller context for event timing or observation duration.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Messenger RNA (mRNA)-Based, Personalized Cancer Vaccine Against Neoantigens Expressed by the Autologous Cancer — NCT03480152.
• Registry record last updated 2020-06-02; status last verified 2020-05.
• Results first posted 2020-04-24.
• 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

NCT03480152 is a National Cancer Institute (NCI)-sponsored Phase I/II trial of a personalized mRNA vaccine targeting neoantigens expressed by a participant’s cancer. The study is listed as nonrandomized, unmasked, and sequential, with enrollment of 5. Its phase I arm descriptions refer to escalating doses; the phase II arm description refers to the maximum tolerated dose established in phase I.

The primary outcome is the number of participants with complete or partial clinical response by RECIST v1.1, assessed up to 12 months. The record lists 6 outcome measures and 0 analyses. It does not report the primary response count, endpoint denominator, statistical analysis, or analysis populations. Serious adverse-event counts are listed for two dose-level groups, with 0 affected in each; the reason for termination is not reported in the registry record.