Study of ADXS-503 With or Without Pembro in Subjects With Metastatic Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of ADXS-503 With or Without Pembro in Subjects With Metastatic Non-Small Cell Lung Cancer (NCT03847519), a non-randomized phase 1, phase 2 study. The primary outcome is Safety/Tolerability of ADXS-503 Monotherapy in Part A and ADXS-503 With Pembrolizumab in Part B: Graded Per Comment Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

2. Clinical Question

3. Trial Design

This was a completed Phase 1/2, open-label study of ADXS-503 alone and with pembrolizumab in metastatic squamous or non-squamous non-small cell lung cancer. The registry lists nonrandomized allocation, no masking, and a sequential model. Enrollment is recorded as 24. The study started on 2019-02-12, and primary completion is recorded as 2022-02-22.

The study was organized into safety and efficacy parts. Part A assessed ADXS-503 monotherapy in people whose disease had become refractory or who were intolerant to standard therapy. Part B assessed ADXS-503 in combination with pembrolizumab. The record describes planned dose escalation in both safety parts. Part C was an efficacy phase using the combination. The listed combination regimen was 1e8 CFU of ADXS-503 plus 200 mg of pembrolizumab. More complete dose-level and treatment-administration details are not reported in the registry record.

The primary safety outcome covered Parts A and B and counted participants with treatment-related adverse events, graded using CTCAE version 4.03, over a timeframe of 12 Months. The registry also lists preliminary objective response rate for Parts A and B and safety and tolerability for Part C among secondary outcomes. Although the study is marked completed, completion status does not itself provide numerical outcome results.

Because allocation was nonrandomized and the study was open-label, participants and investigators were not masked to treatment, and the treatment groups were not created by random assignment. Sequential study parts can differ in eligibility, treatment, and purpose. The registry record does not establish a concurrent control group or a basis for causal comparisons between the parts.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All Treated Subjects Population will include subjects enrolled in the study arms A and B who received at least one dose of study medication

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: All Treated Subjects Population includes subjects enrolled in the study who received at least one dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Safety/Tolerability of ADXS-503 Monotherapy in Part A and ADXS-503 With Pembrolizumab in Part B: Graded Per Comment Terminology Criteria for Adverse Events (CTCAE) Version 4.03, measured over 12 Months.

The primary endpoint is a safety and tolerability measure: the number of participants with treatment-related adverse events in Part A, which used ADXS-503 alone, and Part B, which used ADXS-503 with pembrolizumab. The registry gives a 12 Months timeframe and states that adverse events were graded using CTCAE version 4.03. It defines the primary population as treated subjects enrolled in arms A and B who received at least one dose of study medication.

Counting participants with an event is a binary-outcome approach at the participant level: a participant either meets the event definition during the stated period or does not. This can provide a compact description of how many treated participants experienced treatment-related toxicity. It does not, by itself, describe the number of separate events per participant, their duration, or their clinical course. Those details are not reported in the registry record.

The listed safety summary includes counts of participants affected by serious and other adverse events, but the registry entries do not identify those figures as the primary endpoint’s treatment-related event results. Therefore, they should not be substituted for the primary endpoint. Numerical results for the treatment-related adverse-event measure, including its event definition beyond the registry description, are not reported in the registry record.

Safety endpoints are used to characterize adverse outcomes during exposure to an investigational regimen. Their interpretation depends on how events were collected, graded, attributed to treatment, and followed over time. Further details of those procedures are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are difficult to assess from this record because it reports no outcome analyses. The primary outcome is defined as a count of participants with treatment-related adverse events, while the adverse-event summary separately lists affected participants for serious and other adverse events. The record does not state that those summary categories coincide with the primary endpoint. No confidence intervals, hypothesis tests, adjusted estimates, or analysis populations beyond the primary population description are reported in the registry record.

What does a participant count measure?

General explanation: for a binary event outcome, each participant is classified according to whether the defined event occurred during the specified observation period. A count is easy to interpret, but it does not show how frequently events occurred within a participant, how severe each event was, or when it occurred. A count also depends on the number of participants observed and the completeness and duration of follow-up. The primary outcome’s stated timeframe is 12 Months, but further details about follow-up and event ascertainment are not reported in the registry record.

The adverse-event summary gives group-specific at-risk counts and affected counts. Those counts can be read descriptively within each study part. They should not be treated as an estimate of a causal treatment effect: the arms were not randomized, and the record explicitly cautions that the groups are not a like-for-like control comparison. No statistical adjustment for differences between groups is reported in the registry record.

Why does a confidence interval matter?

General explanation: a confidence interval communicates the uncertainty associated with an estimate. For a binary outcome, an interval around an event proportion can show how compatible the observed data are with a range of underlying event frequencies. Narrower intervals generally indicate greater precision, while wider intervals indicate more uncertainty. No confidence intervals or event proportions for the primary outcome are reported in the registry record. No interval should be inferred from the counts without a stated analysis method and a clear endpoint definition.

What do hypothesis tests add?

General explanation: a hypothesis test evaluates whether data are inconsistent with a specified null hypothesis under a chosen statistical model. A p-value does not measure the size or clinical importance of an effect, and it does not establish that a difference is caused by treatment. The registry record lists no analyses, and no p-values are reported. Even a reported test would require particular caution because treatment assignment was nonrandomized and there was no like-for-like control comparison.

How should the planning assumptions be read?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, its stated convention is participants per arm; for time-to-event outcomes, it is total events. The effect to detect is defined as a stated fraction of the observed effect. These are planning assumptions, not observed trial results and not evidence of the trial’s own design justification. Numerical planning results and the observed effect used in the illustration are not reported in the registry record.

General explanation: a sample-size calculation estimates how much information a future study might need to detect a chosen effect under specified assumptions. Its output is a planning quantity, not a statement about the probability that a completed study’s result is correct. In particular, a planning illustration must not be described as observed power. Its relevance depends on whether the assumed effect, allocation, model, and significance level suit the future study’s question. The registry record does not report a sample-size justification for the trial or further details about the planning illustration.

Why can event-count comparisons mislead?

General explanation: raw counts depend on how many participants are observed and how long they are followed. When exposure time differs, counts alone may not reflect underlying event rates. For adverse events, attribution to treatment, event severity, and repeated events per person also matter. The registry lists at-risk counts and affected counts, but does not give exposure-time analyses or further event-level detail. Comparisons between the sequential parts would also remain confounded by the nonrandomized design, even if a statistical test were calculated.

Over-dispersion is a general issue for count data when variability exceeds what a simple statistical model expects. It can arise, for example, when a small number of participants account for multiple events. The primary endpoint is defined as a participant count, not a count of all event occurrences, and no model-based analysis is reported. The registry record does not provide enough event-level information to assess over-dispersion or select a count model.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Safety Phase Part A - ADXS-503", "Safety Phase Part B - ADXS-503 + 200mg Pembrolizum")
n      <- c(7, 14)
events <- c(4, 11)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Safety Phase Part A - ADXS-503  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3
ARM  Safety Phase Part B - ADXS-503 + 200mg Pembrolizum  14  11  78.6  49.2  95.3  52.4  92.4  51.9  92.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcomes: the primary treatment-related adverse-event measure for Parts A and B, preliminary objective response rate for Parts A and B, and safety and tolerability for Part C. It does not report a multiplicity strategy for interpreting several outcomes or comparisons. In general, examining multiple outcomes can increase the chance of obtaining at least one apparently notable result by chance, depending on the testing plan. No adjustment method, testing hierarchy, or prespecified interpretation procedure is reported in the registry record.

No outcome analyses are listed. Numerical primary-endpoint results, objective response rate results, confidence intervals, and hypothesis tests are not reported in the registry record. As a result, it is not possible to assess how missing observations were handled in an analysis or whether any analysis included all participants intended for that endpoint.

The primary population is described as treated subjects in arms A and B who received at least one dose of study medication. The record does not report the number included in each primary-endpoint analysis, participant-level outcome availability, reasons for missing observations, or a missing-data method. It also does not report whether analyses followed an intention-to-treat principle or another analysis-population rule. Those details are not reported in the registry record.

General explanation: missing outcome data can affect interpretation when the likelihood of being observed is related to a participant’s condition, treatment exposure, or adverse events. A stated analysis population and transparent handling of missing results help readers understand which participants contribute to an estimate. Without that information or numerical endpoint results, the direction and possible influence of missing data cannot be assessed for this study.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac aneurysm (33.3%), ventricular tachycardia (33.3%), urinary tract infection (33.3%), dehydration (33.3%), urinary retention (33.3%).

The registry lists serious and other adverse-event counts separately for each study part. Part A lists 3 participants affected by serious adverse events among 7 at risk and 7 affected by other adverse events among 7 at risk. Part B lists 2 among 14 for serious adverse events and 13 among 14 for other adverse events. Part C lists 3 among 3 for each category. These are descriptive counts, not comparative estimates.

The serious adverse-event terms listed are cardiac aneurysm, ventricular tachycardia, urinary tract infection, dehydration, urinary retention, and pericardial effusion. Their registry percentages are 33.3% for each of the first five terms and 14.3% for pericardial effusion. Term-specific denominators and additional event-level context are not reported in the registry record. The record also lists deaths by part: 5 in Part A, 8 in Part B, and 1 in Part C. Causes and treatment relationships are not reported.

These summaries do not establish whether events were attributed to study treatment, whether an individual could contribute to more than one category, or how long participants were observed. The serious and other event counts should not be read as the primary treatment-related adverse-event endpoint, whose numerical results are not reported in the registry record. Because the study was nonrandomized and its parts were not like-for-like control groups, the counts cannot support a causal comparison of safety between regimens.

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

The registry record establishes that this completed study evaluated ADXS-503 alone and in combination with pembrolizumab in metastatic non-small cell lung cancer, with safety as the primary focus in Parts A and B. It reports descriptive adverse-event counts across Parts A, B, and C and lists serious adverse-event terms and deaths by study part. These registry entries describe what the record contains; they do not provide the numerical result for the primary treatment-related adverse-event outcome.

The record does not report numerical objective response rate results, inferential analyses, confidence intervals, or p-values. It therefore does not support a quantitative conclusion about the magnitude or precision of an efficacy outcome. Nor do the adverse-event summaries, without treatment attribution and event-level context, establish the frequency of treatment-related events as defined by the primary endpoint.

The trial’s nonrandomized, sequential design is central to interpretation. The parts differed in treatment or purpose, and there was no randomized control group. Differences in event counts between parts could arise from the study design or participant characteristics as well as from treatment. The record provides no like-for-like basis for attributing any such difference to a regimen.

General explanation: a descriptive safety count can be useful for documenting events observed in a study, but it is not a substitute for a prespecified comparative analysis. A completed status also does not mean that every result needed to answer a research question is present in the registry record. Here, the primary outcome result and the methods needed to evaluate uncertainty are not reported in the registry record.

Accordingly, the posted information supports a cautious description of the study design and recorded safety summaries. It does not establish a treatment benefit, a lack of benefit, or a causal safety difference between the study parts.

14. Why This Trial Matters Statistically

This study is statistically notable for the gap between a defined primary safety question and the results available in the registry record. The primary endpoint is described as the number of participants with treatment-related adverse events in Parts A and B over 12 Months, but its numerical results are not reported. Separate adverse-event counts are present, yet the record does not establish that they represent this treatment-related endpoint. Keeping endpoint definitions distinct is essential: similarly named safety summaries are not interchangeable without an explicit link in the record.

The design also makes careful interpretation especially important. The trial was open-label and nonrandomized, with sequential parts that examined monotherapy, combination treatment, and an efficacy phase. Those parts do not form randomized comparison groups. Statistical adjustment cannot, by itself, remove all uncertainty about differences in selection or study context when the record does not describe a comparative design or adjustment plan.

Another statistical lesson is the difference between counts and comparative evidence. Counts show how many participants were listed as affected within each part, but without endpoint-specific definitions, uncertainty estimates, and comparable groups, they cannot establish a treatment effect. The record’s lack of reported analyses means readers cannot assess precision or formal evidence for a difference.

The planning assumptions also illustrate why design calculations must be separated from observed results. A planning illustration based on an observed effect and specified assumptions concerns a possible future study’s size; it is not evidence of observed power and does not replace outcome reporting. Numerical planning results and the trial’s own sample-size justification are not reported in the registry record.

Together, these features make the record useful for understanding the study’s structure and the limits of its posted safety summaries. They also show why outcome-specific reporting and clear analysis methods are needed before descriptive findings can answer comparative clinical research questions.

15. 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 registry record does not report numerical results for the primary treatment-related adverse-event endpoint or for the listed objective response rate outcome. It also does not report confidence intervals, p-values, adjusted estimates, or other inferential analyses. This prevents assessment of the precision of the primary outcome or the strength of evidence for any comparison.

The design was nonrandomized, open-label, and sequential. The record explicitly notes that the study arms are not a like-for-like control comparison. Differences between parts may reflect their distinct purposes, treatments, or participant selection, and no causal interpretation of between-part differences is justified by the registry information.

Important details for interpreting safety are not reported in the registry record, including the term-specific denominators, event-level timing, duration of observation, treatment attribution for the listed serious and other events, and causes of the reported deaths. The record does not explain whether participants could be represented in multiple event categories. The primary endpoint’s treatment-related event results cannot be inferred from the separate adverse-event counts.

The primary population is defined as treated subjects in arms A and B who received at least one dose, but the record does not state how many contributed to the primary endpoint analysis or how missing outcome data were handled. Further eligibility and follow-up details, complete dosing information, and a prespecified statistical analysis plan are not reported in the registry record. These gaps limit reproducibility and make it difficult to judge how fully the posted summaries represent outcomes during treatment and follow-up.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of ADXS-503 With or Without Pembro in Subjects With Metastatic Non-Small Cell Lung Cancer — NCT03847519.
• Registry record last updated 2024-06-04; status last verified 2024-05.
• Results first posted 2024-06-04.
• 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.

19. Record Summary

The registry record describes NCT03847519, a completed Phase 1/2, open-label, nonrandomized study of ADXS-503 alone and with pembrolizumab for metastatic squamous or non-squamous non-small cell lung cancer. Enrollment is recorded as 24. The primary outcome was the number of participants with treatment-related adverse events in Parts A and B over 12 Months, graded using CTCAE version 4.03.

The record lists serious and other adverse-event counts for each study part, serious-event terms, and deaths by part. It does not report numerical results for the primary treatment-related adverse-event endpoint, objective response rate, or inferential analyses. Because the parts were not randomized like-for-like comparison groups, the adverse-event counts are descriptive and do not establish causal differences between regimens.