An Efficacy and Safety Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Participants With Advanced Adenocarcinoma of the Lung: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Participants With Advanced Adenocarcinoma of the Lung (NCT03371381), a randomized phase 1, phase 2 study. The primary outcome is Phase 1b: Percentage of Participants With Objective Response.

2. Clinical Question

These details distinguish the clinical question from the evidence available in the registry record. The planned comparison involved two treatment strategies, but the posted primary endpoint concerns the single-arm Phase 1b safety run-in. The record lists 12 participants enrolled overall, without arm-specific enrollment or response counts. It therefore does not give the information needed to estimate or compare objective response between the combination and nivolumab groups. The study is marked terminated; the reason for termination is not reported in the registry record.

3. Trial Design

NCT03371381 is listed as an open-label, randomized Phase 1b/2 study with a parallel-group design and no masking. Its stated purpose was to evaluate JNJ-64041757 plus nivolumab against nivolumab monotherapy in participants with advanced adenocarcinoma of the lung. The registry record lists Janssen Research & Development, LLC as sponsor, an enrollment of 12, and a terminated status.

The study had two parts. Phase 1b was a safety run-in with one arm receiving JNJ-64041757 plus nivolumab. Phase 2 was described as randomized into two groups: Group A received the combination, and Group B received nivolumab alone. The available record does not state how many participants entered each part, how many were assigned to each Phase 2 group, or how many completed treatment. It also does not report the randomization procedure or allocation ratio.

The combination arm description says that participants received separate intravenous infusions of the two agents during treatment cycles. The nivolumab arm description also specifies intravenous infusion. Treatment was described as continuing until listed stopping circumstances, including disease progression or unacceptable toxicity; additional stopping details are not fully available in the record. Those descriptions do not establish how treatment was administered in practice to the enrolled participants.

The study began on 2018-01-02, and the listed primary completion date is 2018-10-09. The record does not report the reason for termination, whether recruitment or follow-up ended as planned, or whether the Phase 2 comparison generated analyzable results. The overall enrollment is small, and the lack of arm-specific counts further limits interpretation of the intended randomized comparison.

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: The trial consisted of two parts (Phase 1 b and Phase 2). However, Phase 2 was not conducted due to early termination of the study. All analyses were performed on Phase 1b data.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The all treated analysis population consisted of participants who received at least 1 dose of study agent.

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 all treated analysis population consisted of participants who received at least 1 dose of study agent.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1b: Percentage of Participants With Objective Response, measured over Up to 6.8 Months.

The listed Phase 1b primary endpoint is the percentage of participants with an objective response, assessed up to 6.8 Months. Objective response means achieving either a complete response or a partial response according to RECIST version 1.1. In the registry description, complete response involves disappearance of all lesions, with lymph nodes non-pathological in size and tumor marker level normalized. Partial response requires at least a 30 percent decrease in the sum of diameters of target lesions compared with baseline, without new lesions or unequivocal progression of nontarget lesions.

An objective response endpoint reduces tumor assessments to a defined category: a participant either meets the response criteria or does not. It is often useful for describing the proportion of participants whose measured disease meets a specified response threshold during the assessment period. The percentage is interpretable only with its denominator, response count, assessment rules, and handling of participants without an evaluable assessment.

The listed analysis population includes participants who received at least 1 dose of study agent. The record does not report the number analyzed, the number with a complete or partial response, or the resulting percentage. It therefore does not provide an estimate of the Phase 1b response rate or its precision. This Phase 1b endpoint is also not, by itself, a reported comparison of the randomized Phase 2 groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help separate what an endpoint measures from how much confidence can be placed in its estimate. The registry record identifies an objective-response endpoint and an analysis population, but it does not report an outcome count, estimate, confidence interval, or analysis. The explanations below describe general statistical concepts; they do not imply that a particular method was used in this study.

What does an objective-response percentage represent?

For a binary endpoint, each participant is classified into one of two categories, such as meeting or not meeting a response definition. The percentage is the response count considered in relation to the analysis denominator. Its interpretation depends on consistent outcome assessment and a clearly specified rule for participants whose response status is unknown or whose assessments are incomplete. Here the registry defines objective response using complete or partial response under RECIST version 1.1, and defines the all-treated analysis population as those receiving at least 1 dose. It does not report the count or percentage for that population.

A confidence interval is a range of values that conveys sampling uncertainty around an estimate under a specified statistical procedure. It is not a guarantee that the true value lies in that particular interval, and its width depends in part on the amount of information and the variability in the data. No confidence interval for the primary endpoint is reported in the registry record. Without an endpoint estimate and interval, neither the response level nor its precision can be evaluated.

Why does the design matter for interpretation?

The study includes a one-arm Phase 1b safety run-in and a randomized Phase 2 comparison. A single-arm response percentage describes outcomes in that arm; without a concurrent comparison, it does not isolate the effect of the combination from other explanations for observed outcomes. Randomization in Phase 2 is intended to support a fair comparison of groups, but interpretation still requires reported group-specific outcomes, denominators, and an analysis that respects the allocation. The registry record does not provide those Phase 2 results.

Open-label means masking was absent. As a general matter, awareness of treatment assignment can influence care, reporting, or outcome assessment, although a defined response criterion can help standardize measurement. The record does not describe independent review or other procedures for limiting assessment bias. It would be inappropriate to assume that such procedures were or were not used.

What is over-dispersion?

Over-dispersion is a general issue in statistical models for counts or rates when the observed variability exceeds what a model assumes. If ignored, uncertainty estimates can be too narrow. It is not a direct feature of a simple binary percentage in the same way it can be for count data. The record does not report a model for the primary endpoint, and no over-dispersion assessment is reported. No claim about its use or relevance in the study's analysis can therefore be made.

How should planning illustrations be understood?

Sample-size planning asks how many participants would be needed under chosen assumptions to target a specified level of statistical power for a planned comparison. The registry record does not report the study's own sample-size justification or the assumptions used to set its enrollment. Planning illustrations based on an observed effect are distinct from the trial's design rationale and are not observed power. The record does not provide a primary-outcome effect estimate from which such an illustration could be interpreted.

The listed general assumptions for any planning illustration are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated share of the observed effect. These are described as illustration assumptions, not as the protocol's design assumptions. For time-to-event outcomes, the illustration convention is total events; for other outcomes, it is participants per arm. No study-specific sample-size justification, target power, or planned effect is reported in the registry record.

What does a significance test add?

A significance test evaluates how compatible observed data are with a specified null hypothesis under a statistical model. A p-value does not measure the probability that a treatment works, the size of an effect, or the practical importance of a result. Since the registry record reports no primary analysis and no p-value, there is no test result to interpret. In general, effect estimates and their uncertainty are more informative than a threshold-based conclusion alone.

These methods explain what would be needed to assess an efficacy result, but they cannot substitute for results. In this record, the endpoint definition and study design are described, while the outcome estimates and statistical analysis are absent.

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: JNJ-64041757+ Nivolumab")
n      <- c(12)
events <- c(0)
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: JNJ-64041757+ Nivolumab  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, groups, time points, or statistical tests. Repeated testing can increase the chance of finding at least one apparently notable result by chance. A statistical plan may address this through a prespecified hierarchy or an adjustment, but the registry record does not report a multiplicity strategy. It also does not report an analysis plan specifying which outcome or comparison would control a family of tests.

The record lists nine secondary outcome measures, including duration of objective response, progression-free survival events, overall survival events, treatment-emergent adverse events, blood culture and bacterial shedding measures, nivolumab concentrations, and anti-nivolumab antibodies. Listing these outcomes does not show that results were collected or analyzed. No analyses are listed in the record, and no secondary outcome estimates are reported.

The primary endpoint's stated analysis population consists of participants who received at least 1 dose of study agent. The record does not report how many participants were included in that population or how participants without an evaluable response assessment were handled. It does not describe imputation, censoring, sensitivity analyses, or other missing-data procedures. These omissions matter because different approaches to unknown outcomes can change the denominator and interpretation of an endpoint.

The registry record also does not report whether analysis populations differed across outcomes, whether participants were analyzed according to randomized assignment for Phase 2, or how protocol deviations were treated. Such methods should not be inferred from the randomized design. Without outcome analyses or an explanation of missing data and multiplicity, readers cannot assess the robustness of any efficacy conclusion from the posted record.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonitis (16.7%), abdominal pain (8.3%), intestinal obstruction (8.3%), non-cardiac chest pain (8.3%), oedema peripheral (8.3%).

The safety entries refer to the Phase 1b JNJ-64041757 plus nivolumab group. The record lists 12 participants at risk for serious adverse events and 5 participants affected. It separately lists 12 at risk for other adverse events and 12 affected. These are counts, not a comparison with the nivolumab-only group; the record does not provide corresponding Phase 2 safety figures for that arm.

The listed serious adverse-event terms include pneumonitis at 16.7%, and abdominal pain, intestinal obstruction, non-cardiac chest pain, oedema peripheral, and arthralgia at 8.3% each. These percentages are registry entries for listed terms. The record does not clarify whether participants could have more than one event, how event terms were selected for display, or whether the events were judged related to treatment. They should not be added or treated as mutually exclusive categories.

Five deaths are recorded among the 12 at risk in the combination group. The causes, timing, and relationship of the deaths to study treatment are not reported. A death count in a treatment group is not, by itself, evidence that treatment caused the deaths. Because the study was small and the available safety counts are not comparative, the entries do not establish differences in safety between the study regimens.

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

The registry record establishes that NCT03371381 was designed to evaluate a combination of JNJ-64041757 and nivolumab in a Phase 1b safety run-in and a randomized Phase 2 comparison with nivolumab alone. It also identifies objective response as the Phase 1b primary endpoint and defines response using RECIST version 1.1. These details describe the study question and its measurement approach.

The record does not report the primary endpoint result, an efficacy analysis, or a comparison between randomized groups. It therefore cannot show how often participants responded, how precisely that response rate was estimated, or whether the combination differed from nivolumab alone. Enrollment of 12 is reported for the study overall, but the record does not give arm-specific enrollment or endpoint denominators.

The safety entries provide counts and listed serious adverse-event terms for the Phase 1b combination group. They do not provide a complete comparative safety analysis. The five deaths recorded in that group have no reported cause or treatment attribution, so they cannot be interpreted as treatment-caused deaths from these entries alone.

The terminated status is a record status, not an explanation. The reason for termination is not reported in the registry record. It does not, on its own, establish whether a treatment was beneficial, harmful, or ineffective, nor does it indicate why the study stopped. Likewise, an absent analysis is not a result showing no effect; it is a lack of a posted estimate to evaluate.

The most defensible reading is therefore limited: the study's design, population, treatment groups, and endpoint definition are described, and a small set of safety counts is posted. The efficacy question remains unanswered by the reported results. Any conclusion about comparative efficacy, precision, or treatment attribution would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical-trial interpretation: a well-defined question and endpoint do not themselves constitute evidence about the endpoint. The record describes a randomized Phase 1b/2 design, the treatment groups, and a RECIST-based objective-response definition. Yet it does not report the primary outcome or a Phase 2 comparison. Statistical interpretation must begin by checking whether estimates and denominators are actually available.

The design also highlights that different study parts answer different questions. A safety run-in with one combination arm can describe experience in that group, while a randomized comparison is needed to estimate differences between assigned treatment strategies. The registry record's primary endpoint is listed for Phase 1b, so it should not be mistaken for a reported randomized treatment effect.

Small overall enrollment is another reason to attend closely to denominators and uncertainty. The record lists 12 participants but does not divide them by phase or arm. Without those details and outcome counts, neither response percentages nor the precision of a comparison can be assessed. This is a general lesson in reading trial reports: a total enrollment figure is not a substitute for analysis-population counts.

Finally, the record demonstrates why status and safety entries require careful interpretation. Termination does not disclose a reason, and event counts do not establish causation or a comparative safety difference. Separating description from inference prevents unsupported conclusions when a registry entry contains design information and some safety data but no posted efficacy analysis.

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 main trial-specific limitation of the posted record is the absence of a primary-outcome result. No response count, analysis denominator, response percentage, confidence interval, or statistical test is reported. The randomized Phase 2 comparison also has no group-specific efficacy estimates in the record, so the intended comparison cannot be evaluated from the posted results.

The total enrollment is 12, but the record does not report how many participants entered Phase 1b or Phase 2, how many were assigned to each randomized group, or how many were included in each analysis. This prevents assessment of the information available for an estimate and makes it impossible to relate the listed safety counts to a randomized comparison.

The record does not report the reason for termination, the protocol's sample-size justification, the statistical analysis plan, or interim analyses. It does not describe multiplicity control, outcome assessment procedures beyond the RECIST definition, handling of missing data, or the treatment of protocol deviations. These details should not be inferred from the study design or endpoint listing.

Safety information is limited to the posted Phase 1b combination-group entries. The record does not state whether listed events were treatment-related, provide causes or attribution for deaths, or give comparable safety counts for the nivolumab-only group. These limitations restrict interpretation of both efficacy and safety; they do not establish that an unreported outcome was favorable or unfavorable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Efficacy and Safety Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Nivolumab Versus Nivolumab Monotherapy in Participants With Advanced Adenocarcinoma of the Lung — NCT03371381.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2019-12-11.
• 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

NCT03371381 is listed as a randomized, open-label, parallel Phase 1b/2 study of JNJ-64041757 plus nivolumab versus nivolumab alone in advanced lung adenocarcinoma. The record describes a one-arm Phase 1b safety run-in and a two-group randomized Phase 2 part. Overall enrollment is 12, and study status is terminated.

The Phase 1b primary endpoint is the percentage of participants with an objective response under RECIST version 1.1. No primary-outcome analysis or randomized efficacy comparison is reported. Safety entries for the Phase 1b combination group list 12 participants at risk for other adverse events and 5 at risk for serious adverse events; five deaths are recorded. Causes and treatment attribution are not reported. The reason for termination, statistical analysis plan, sample-size justification, and missing-data methods are not reported in the registry record.