A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer (NCT02795988), a randomized phase 1, phase 2 study. The primary outcome is Phase 1b: Number of Participants With Adverse Events (AEs).

2. Clinical Question

3. Trial Design

NCT02795988 is a phase 1b/2 study of IMU-131 with chemotherapy in HER2-positive advanced gastric cancer. The registry reports an enrollment of 64 and a completed status. The recorded start date is 2017-08-30 and the primary completion date is 2024-03-20. Imugene Limited is listed as the sponsor.

The design combines an open-label, multicenter dose-escalation phase 1b study with a randomized, open-label phase 2 comparison. In phase 1b, the stated purpose was to assess safety, tolerability, immunogenicity, and a recommended phase 2 dose. The phase 2 study evaluated IMU-131 plus standard-of-care chemotherapy against standard-of-care chemotherapy alone. The record also reports a phase 2 extension with IMU-131 100 μg and 200 μg groups. Those extension groups should not be read as part of the randomized chemotherapy-only comparison.

The registry classifies the study as parallel and randomized, and records single masking, while the study descriptions characterize the phase 1b and phase 2 portions as open-label. How the masking classification relates to the open-label descriptions is not explained in the registry record. Allocation procedures, the randomization ratio, and details of any stratification are not reported in the registry record.

The posted primary endpoint is confined to phase 1b and counts participants with adverse events. The phase 2 and extension outcomes include measures of disease control and response, as well as time-to-event and tumor-size outcomes. The primary endpoint therefore does not itself provide a randomized phase 2 estimate of comparative efficacy. The registry record does not report a detailed protocol rationale for the study’s sample size.

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: A total of 64 participants were enrolled in the study. Phase 1b, Phase 2, and Phase 2 extension parts enrolled separate participant populations.

Only the first 6 of 7 groups are shown.

Phase 1b

Reasons for not completing this period:

Phase 2

Reasons for not completing this period:

Phase 2 Extension

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety population included all randomized participants who received any amount of study treatment.

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: The Intent-to-Treat (ITT) Population included all randomized participants.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1b: Number of Participants With Adverse Events (AEs), measured over Up to approximately 7 months.

The primary endpoint counts phase 1b participants with adverse events, with the timeframe stated as up to approximately 7 months. An adverse event is defined in the registry as any untoward medical occurrence in a participant who received study drug, without regard to whether a causal relationship was possible. The endpoint is therefore a participant count, not a count of all event episodes, and it does not by itself establish that treatment caused an event.

Safety counts are useful in an early dose-escalation study because they describe how many participants experienced an untoward medical occurrence while receiving study treatment. The phase 1b arms report counts of 3 at 10 μg, 6 at 30 μg, and 5 at 50 μg. These counts are presented alongside the corresponding arm sizes of 3, 6, and 5. The registry does not provide a confidence interval or a comparative statistical test for this primary endpoint.

The endpoint should not be mistaken for the phase 2 randomized efficacy question. It does not measure tumor response, progression, or survival, and the posted primary result is not a comparison with chemotherapy alone. The registry describes serious adverse events and other non-serious adverse events separately in its adverse-event reporting. That separate reporting gives additional safety context but does not turn the phase 1b count into an estimate of treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on distinguishing the endpoint, the population, and the comparison. The primary endpoint is a count of phase 1b participants with adverse events. The phase 2 disease control and objective response outcomes are percentages, and their posted comparisons use risk differences. These are different types of summaries and answer different questions. A safety count describes participants with an event; a risk difference describes the contrast between the proportions with an outcome in two groups.

What does an 80% confidence interval convey?

A confidence interval expresses uncertainty around an estimate under the statistical method used. A narrow interval indicates greater precision than a wide interval, while an interval that spans the value corresponding to no difference leaves the direction and size of the comparison uncertain. The registry reports 80% confidence intervals for the phase 2 and extension disease control and objective response percentages. These intervals are not guarantees about the true value, and their interpretation depends on the method and assumptions used. The interval level is less demanding than a higher-coverage interval would be, so readers should note the stated 80% level rather than treat these bounds as a conventional higher-coverage interval.

The phase 2 comparison estimates also have uncertainty intervals for risk differences, and those intervals cross no difference for both posted outcomes. This is consistent with the wide intervals around the arm-specific percentages. It does not prove that the treatment groups have the same outcome. Rather, the posted data do not pin down a precise comparative effect. The registry does not report sponsor analyses for these comparisons, so the displayed comparison statistics should be read as unadjusted estimates rather than as a replacement for a prespecified trial analysis.

How should the p-values be read?

The unadjusted p-values reported for disease control rate and objective response rate are 0.681 and 0.53. A p-value measures how compatible the observed data are with a specified null model, given the model assumptions; it is not the probability that a treatment works, nor does it quantify the clinical importance of an estimate. These values are unadjusted. The registry record does not report whether the study planned a multiplicity adjustment, what testing hierarchy might have been used, or how these results relate to a formal confirmatory analysis. They should therefore not be interpreted as definitive evidence for or against a treatment effect.

Why does the small sample matter?

When group sizes are small, each participant can substantially affect a percentage, and estimates can vary considerably across samples. That makes the width of the uncertainty intervals especially important. The phase 2 outcome groups contain 18 participants in the IMU-131 plus chemotherapy arm and 14 in the chemotherapy-only arm for the reported comparisons. The extension groups each contain 7 participants. Those extension estimates are particularly descriptive and are not randomized comparisons against the chemotherapy-only group. No method can make the observed estimates more precise than the underlying information allows.

The record’s sample-size illustrations use the observed effect as a planning reference, with assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. They illustrate hypothetical future study sizes for detecting specified fractions of the observed effect. They are not the original trial’s sample-size justification, which is not reported in the registry record, and they are not observed power. Because the observed effects themselves are uncertain, planning directly from them can be unstable; the illustrations should not be read as evidence that the trial was adequately powered or as a recommended design.

What are the limits of the posted analyses?

The record lists one analysis and does not list reported analyses for the phase 2 disease control and objective response comparisons. It does not describe adjustment for baseline characteristics, the handling of missing outcome data, or detailed analysis populations for those secondary outcomes. Nor does it specify whether the posted comparison estimates follow an intention-to-treat approach. These omissions limit assessment of whether the estimates reflect the randomized population and whether the statistical analysis followed a prespecified plan.

Over-dispersion is a general concern when observations vary more than a chosen statistical model expects; a model that ignores that extra variability can understate uncertainty. The posted binary outcomes are simple participant proportions, and the registry does not report a model-based analysis that allows readers to assess over-dispersion. This does not mean over-dispersion was present; the relevant modeling details are not reported in the registry record. For these data, the central practical considerations are the small groups, wide intervals, unadjusted secondary comparisons, and absent analysis details.

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("Phase 1b: 10 μg IMU-131 Plus Chemotherapy", "Phase 1b: 30 μg IMU-131 Plus Chemotherapy", "Phase 1b: 50 μg IMU-131 Plus Chemotherapy")
n      <- c(3, 6, 5)
events <- c(3, 6, 5)
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  Phase 1b: 10 μg IMU-131 Plus Chemotherapy  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Phase 1b: 30 μg IMU-131 Plus Chemotherapy  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase 1b: 50 μg IMU-131 Plus Chemotherapy  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven secondary outcomes and reports unadjusted p-values for the phase 2 disease control rate and objective response rate comparisons. It does not report a multiplicity strategy, such as an order for testing outcomes or an adjustment to account for examining multiple outcomes. Without that information, the unadjusted p-values should be regarded as exploratory. They do not by themselves control the overall chance of a false-positive finding across the outcome set.

Missing-data methods are not reported in the registry record. The record does not explain how participants with unavailable response assessments, incomplete follow-up, or other missing outcome information were handled. It also does not report whether sensitivity analyses were conducted to examine the impact of missingness. Consequently, the posted percentages cannot be fully assessed for possible bias from missing data based on the registry record alone.

The primary endpoint description identifies a safety population as all randomized participants who received any amount of study treatment. That description does not provide a detailed account of how the phase 1b dose groups were assembled or how the phase 2 secondary outcome populations were defined. The analysis population for the randomized phase 2 comparisons, including whether all randomized participants were analyzed in their assigned groups, is not reported in the registry record.

Other analysis details are also absent: the planned handling of protocol deviations, the precise statistical models, any covariate adjustment, and the treatment of censoring for time-to-event outcomes are not reported in the registry record. The registry lists a completed study, but completion status does not resolve these methodological uncertainties. These reporting gaps do not demonstrate that the analyses were inappropriate; they limit independent evaluation of how the reported estimates were produced and how robust they are.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (33.3%), hypokalaemia (33.3%), seizure (33.3%), acute kidney injury (33.3%), anaemia (20.0%).

The registry reports serious adverse events separately from other non-serious adverse events. In phase 1b, serious adverse events affected 2 of 3 participants in the 10 μg group, 4 of 6 in the 30 μg group, and 3 of 5 in the 50 μg group. The corresponding counts for other non-serious adverse events are 3 of 3, 6 of 6, and 5 of 5. These are participant counts within each reported group, not counts of separate event episodes.

For phase 2, serious adverse events affected 2 of 19 participants in the IMU-131 plus chemotherapy group and 5 of 17 in the chemotherapy-only group. Other non-serious adverse events affected 18 of 19 and 15 of 17, respectively. In the phase 2 extension, serious adverse events affected 0 of 7 participants at 100 μg and 2 of 7 at 200 μg; other non-serious adverse events affected 7 of 7 and 5 of 7. The registry also lists deaths in these groups, but does not state that the deaths were caused by study treatment.

The adverse-event definition does not require a causal relationship, and the serious-event summary includes events regardless of causality. The listed serious-event terms include neutropenia, hypokalaemia, seizure, acute kidney injury, anaemia, and febrile neutropenia. Group sizes are limited, and these descriptive counts should not be treated as adjusted comparisons or as evidence that an event was caused by a particular treatment.

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

The posted results describe adverse events in the phase 1b dose groups and report phase 2 and extension estimates for selected secondary outcomes. The primary endpoint is a safety count; it does not answer whether adding IMU-131 changes disease control, response, progression, or survival compared with chemotherapy alone. The randomized phase 2 comparisons are relevant to that treatment contrast, but the estimates are imprecise and the registry does not report sponsor analyses for them.

The disease control and objective response estimates should be read with their 80% confidence intervals and unadjusted p-values. The intervals show substantial uncertainty, and the risk-difference intervals include no difference. This does not establish equivalence or rule out clinically important effects in either direction. It also does not support a claim that IMU-131 improves outcomes. The extension results are separate, small-group observations rather than randomized comparisons with chemotherapy alone.

The safety counts identify participants with events, but the registry’s definition does not establish causation. Serious adverse events and deaths should be considered in the context of the population, follow-up, and treatment received. The posted counts alone cannot establish whether the observed events resulted from IMU-131, chemotherapy, the cancer, or other factors.

Several details needed for a fuller assessment are not reported in the registry record, including the missing-data approach, the phase 2 analysis population, the multiplicity plan, and detailed statistical methods. The posted results are therefore best understood as descriptive and exploratory evidence, not as a complete account of a prespecified confirmatory analysis. They can characterize what was observed in the reported groups, while leaving substantial uncertainty about comparative effects and their precision.

14. Why This Trial Matters Statistically

This trial raises several important statistical issues for clinical researchers. Its phases address different questions: phase 1b reports adverse-event counts across dose groups, while phase 2 compares IMU-131 plus chemotherapy with chemotherapy alone. Keeping these questions separate prevents a safety endpoint from being mistaken for an efficacy comparison and prevents extension observations from being treated as randomized evidence.

Precision is central to interpreting the phase 2 results. The posted confidence intervals are wide, and the estimated comparative effects remain compatible with no difference. A numerical contrast between group estimates may draw attention, but without sufficiently precise evidence it does not establish the direction or size of a treatment effect. The unadjusted p-values likewise cannot resolve the uncertainty or demonstrate equivalence.

The record also illustrates why statistical conclusions depend on transparent methods reporting. The analysis population, missing-data handling, multiplicity strategy, and detailed inferential plan are not reported in the registry record. Those choices can affect how outcomes are estimated and how strongly results support a conclusion. A completed status and a set of posted estimates do not substitute for those details.

Finally, planning illustrations based on observed effects must be distinguished from the trial’s design and from observed power. The registry states that these are planning illustrations under specified assumptions, not the trial’s own design justification. Because observed effects are uncertain, such illustrations are useful only as conditional planning aids. Together, these points make the study a useful example of why endpoint definitions, analysis populations, uncertainty intervals, and reporting transparency all matter when reading clinical trial results.

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 offers limited detail for evaluating the phase 2 comparisons. It does not report the randomization ratio, allocation procedures, stratification factors, or detailed statistical plan. Although the study is described as open-label and the registry records single masking, the relationship between those descriptions is not explained. The absence of these details limits assessment of potential bias and of how the planned analysis was implemented.

Small group sizes constrain precision, especially in the extension groups, which contain 7 participants at each reported dose. The secondary outcome intervals are broad, and the registry does not report numerical results for every listed secondary outcome in the posted results. The extension groups also do not provide a randomized chemotherapy-only comparison. Their estimates should therefore be treated as descriptive rather than as evidence of a comparative dose effect.

For the phase 2 secondary results, the record gives unadjusted comparisons but no reported sponsor analyses. It does not report adjustment for multiple outcomes, missing-data methods, or detailed analysis-population definitions. The posted comparisons may consequently not capture all features of the prespecified analysis, if any; those details are not reported in the registry record. The record also does not provide enough information to assess the handling of censoring for its time-to-event outcomes.

Safety interpretation has its own limits. Adverse events are counted without regard to causal relationship, and the reported deaths are not attributed to treatment in the record. Group counts can describe what was observed but cannot establish causation. Finally, the planning illustrations use observed effects and stated assumptions; they do not establish that the completed trial was designed with adequate power. These limitations call for cautious interpretation rather than a categorical efficacy or safety conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of IMU-131(HER-Vaxx) and Chemotherapy Compared to Chemotherapy Only in Patients With HER2 Positive Advanced Gastric Cancer — NCT02795988.
• Registry record last updated 2025-04-16; status last verified 2025-03.
• Results first posted 2025-04-16.
• 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

NCT02795988 is a completed phase 1b/2 study sponsored by Imugene Limited. It enrolled 64 participants and examined IMU-131 with chemotherapy in HER2-positive advanced gastric cancer. Phase 1b assessed safety, tolerability, immunogenicity, and a recommended phase 2 dose; phase 2 was a randomized, open-label comparison with chemotherapy alone.

The posted primary endpoint counts phase 1b participants with adverse events up to approximately 7 months. Posted phase 2 secondary results include disease control rate and objective response rate, with 80% confidence intervals and unadjusted comparisons. The phase 2 estimates are uncertain, and the registry does not report sponsor analyses for those comparisons. Extension results are descriptive and do not form the randomized chemotherapy-only comparison.

The registry record does not report the multiplicity plan, missing-data methods, detailed phase 2 analysis populations, or full statistical plan. The results support a descriptive reading of the reported outcomes, not a definitive conclusion about comparative efficacy or causation of adverse events.