A Study of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Advanced Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Advanced Melanoma (NCT03711188), a na phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

3. Trial Design

This completed study was a phase 2, single-group trial of IMM-101 in combination with checkpoint inhibitor therapy in advanced melanoma. The registry record lists an enrollment of 16. Allocation is recorded as not applicable, and masking as none; the record therefore does not describe random assignment or masking. There is no randomized control group for estimating a treatment contrast.

Cohort A received IMM-101 with nivolumab. Cohort B participants who failed to respond to IMM-101 and nivolumab and met certain criteria had the option to change treatment on study to IMM-101 with ipilimumab. The treatment path in cohort B was thus conditional on response and eligibility, rather than a parallel assigned regimen for all participants. The registry record does not report how many participants were in each cohort at enrollment or how many changed treatment.

The study start date is 2018-10-04, and the primary completion date is 2021-12-02. The registry lists the study status as completed. The primary outcome timeframe is from enrollment to the end of study, stated as 18 months, or withdrawal, whichever was soonest. The response assessment window differed by cohort: through the 12-month assessment for cohort A, and through the 6-month assessment or the last assessment before a treatment change for cohort B, whichever was sooner.

The record identifies best overall response, progression-free survival, overall survival, and overall survival at one year among secondary outcomes. It does not report a randomized comparison or a detailed statistical plan. The response endpoint is defined separately within each cohort; it is not evidence of a direct comparison between the two treatment combinations.

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: Twenty-two patients at 2 centres were consented and screened. Six patients failed to meet one or more of the specific inclusion criteria or met one or more exclusion criteria and were deemed screen failures.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set (SAF) included all patients who received at least one dose of IMM-101, irrespective of compliance with eligibility and other protocol criteria.

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 baseline analysis population included all patients with confirmation of eligibility at Screening.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate, measured over From enrollment to end of study (18 months) or withdrawal, whichever was soonest.

The primary endpoint was overall response rate, defined as the number of participants with a confirmed complete response or partial response as their best overall response, divided by the number in the intent-to-treat analysis set in each cohort. Best overall response was determined by the investigator according to RECIST 1.1. The registry record does not report the resulting response counts, cohort denominators, or response rates.

As a general statistical concept, an overall response rate expresses the observed frequency of a specified response in a defined population. It can describe tumor response during a stated assessment period, but it does not by itself compare treatment with a control or show how outcomes would have differed under another treatment. Interpretation also depends on how responses are confirmed, which assessments contribute, and how participants without an evaluable response are handled.

The response window was not identical between cohorts. Cohort A’s best overall response was determined using data through the 12-month assessment. Cohort B’s window extended through the 6-month assessment or the last assessment before a change to IMM-101 with ipilimumab, whichever was sooner. These cohort-specific windows matter when describing the endpoint and caution against treating the response results, if reported elsewhere, as if they arose from identical follow-up.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a cohort-specific response proportion. Its numerator is the number of participants whose best overall response was a confirmed complete response or partial response; its denominator is the intent-to-treat population in that cohort. The registry record defines this calculation but does not report either the numerator or denominator for the primary outcome. The overall enrollment figure alone cannot substitute for cohort-specific denominators.

What does a response proportion describe?

As a general statistical explanation, a proportion describes the share of a defined group meeting a specified outcome. Its interpretation depends on a clear outcome definition, a defined population, and a consistent observation window. Here, the response definition requires confirmation and investigator determination according to RECIST 1.1. Best overall response is based on the best qualifying response recorded within the outcome’s stated assessment window, not simply on whether a participant had any single scan with a favorable designation.

The endpoint’s intent-to-treat denominator is important because it identifies the population to which the response proportion is meant to refer. The registry record does not give further details about the precise membership of that analysis set, how missing assessments were treated, or whether participants who changed treatment remained in the relevant denominator. These details are needed to reproduce or fully interpret an analysis.

Why does the assessment window matter?

The response determination uses different stated windows for the cohorts. Cohort A’s best overall response was based on confirmed responses recorded between the first post-screening scan and the last scan at or before the 12-month assessment. For cohort B, the relevant period ended at the 6-month assessment or the last assessment before changing to IMM-101 with ipilimumab, whichever was sooner. Because the observation periods and treatment pathways differ, any cohort-level response summaries would need to be read in the context of those definitions rather than assumed to represent the same follow-up opportunity.

As a general point, different follow-up windows can affect the opportunity to observe an event. A shorter window may yield less time for an outcome to occur or be confirmed. That does not establish the direction or size of any difference in this study; the registry record does not report the primary response results or analyses that would address such questions.

How should uncertainty be considered?

A response proportion is an estimate based on observed participants, not a guarantee of the response frequency in another group or setting. In general, a confidence interval communicates uncertainty around an estimate and is particularly relevant when the analyzed group is limited. The registry record does not report an interval for the primary endpoint. It also does not specify the method used to calculate an interval or any test for the endpoint. No inference about statistical significance or precision should be attributed to the record.

General methods for a binary endpoint can include interval estimation for a proportion and, when appropriate, tests against a prespecified reference value or contrasts between groups. Those approaches require a stated analysis plan and relevant observed data. Neither a reference value nor an inferential analysis is reported in the registry record. Since the study is single-group, a direct randomized treatment contrast is not available in the design described.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations are described as giving a total event count using the Schoenfeld approach; other illustrations are described as participants per arm. These are planning assumptions, not evidence that the study used those methods to analyze its outcomes.

Planning calculations estimate what a hypothetical design might require under specified assumptions. They do not represent observed power, and they do not establish what effect this trial found. The registry record does not report an observed primary response effect in the information available for this analysis, nor does it provide the numerical planning results. The illustrations therefore cannot fill the gap in the primary outcome results.

More generally, normal approximations and other statistical procedures rely on assumptions about the data and design. Their appropriateness depends on the endpoint, sample size, event pattern, and analysis plan. The registry record does not report enough detail to assess those assumptions for a trial analysis. No particular inferential method should be inferred from the endpoint definition or from the planning assumptions alone.

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("Cohort A", "Cohort B")
n      <- c(11, 5)
events <- c(8, 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  Cohort A  11  8  72.7  39.0  94.0  43.4  90.3  42.8  90.1
ARM  Cohort B  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcomes, including best overall response, progression-free survival, overall survival, and overall survival at one year. Assessing several outcomes can raise a multiplicity question: if many hypotheses are tested, the chance of at least one apparently unusual result may differ from the chance for a single prespecified test. As a general statistical matter, an analysis plan may address this by defining a primary outcome, setting a testing order, or adjusting inference. The registry record does not report a multiplicity strategy or a detailed statistical analysis plan.

The primary endpoint is defined for the intent-to-treat analysis set in each cohort, but the registry record does not provide further detail on the analysis population, including how missing or unevaluable response assessments were handled. The record states that the response observation period ended at study completion or withdrawal, whichever was soonest, and supplies cohort-specific response assessment windows. It does not report the extent or reasons for missing assessments, or any imputation or sensitivity analysis for missing outcome data.

The record does not describe a randomized analysis population, a per-protocol population, or a method for addressing departures from the treatment path. Cohort B could change treatment after not responding and meeting criteria. How response after a change was handled in any analysis is not reported in the registry record. These omissions limit the ability to reproduce the endpoint analysis and assess how robust it is to missing data or treatment changes.

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: diarrhoea (100.0%), atrioventricular block (6.2%), pneumonia (6.2%), epistaxis (6.2%), pyrexia (6.2%).

The registry record lists serious adverse events, other adverse events, and deaths by treatment group. For IMM-101 and nivolumab, 16 participants were at risk for serious adverse events and 12 were affected; 16 were at risk for other adverse events and 16 were affected, and 8 deaths are listed. For IMM-101 and ipilimumab, 1 participant was at risk and 1 was affected for serious adverse events; the same at-risk and affected counts are listed for other adverse events, with 1 death.

The record also lists serious adverse event terms with percentages: Diarrhoea, 100.0%; Atrioventricular block, Pneumonia, Epistaxis, Pyrexia, and Chills, each 6.2%. The registry information does not give further term-level counts or denominators in the registry record, so the percentages should not be treated as a complete account of event frequency or severity.

These are descriptive safety figures. They do not establish that a treatment caused an event or death. The groups are not randomized controls, and the ipilimumab group’s reported at-risk count is 1. Differences between the group figures should therefore not be read as a reliable comparative estimate of safety.

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

The study addresses a relevant statistical question: whether confirmed complete or partial responses were observed with IMM-101 combined with checkpoint inhibitor therapy in advanced melanoma. Its primary outcome definition is clear about the response categories and the use of investigator-assessed RECIST 1.1, and it specifies a cohort-specific intent-to-treat denominator. But the registry record does not report the response counts, denominators, or rates. The primary outcome’s observed result and precision therefore cannot be stated from the record information.

The design also shapes what any result could mean. This was a single-group study, not a randomized comparison against a control. Cohort B’s treatment change was optional for participants who failed to respond to the initial combination and met criteria. Because cohort membership and subsequent treatment were not described as randomized, comparisons between cohorts would be vulnerable to differences in participant circumstances and treatment history. They would not show the effect of choosing one combination over the other.

More generally, an observed response proportion is a description of outcomes in the analyzed group during a defined period. It does not by itself establish that treatment caused the observed responses, predict an individual’s outcome, or show how the group would have fared under another treatment. Those are different questions and require additional evidence and appropriate designs or assumptions.

The safety counts should likewise be read descriptively. Counts of participants affected and deaths do not, without a suitable comparative design and fuller context, identify treatment effects. The record’s safety group with one participant at risk offers especially limited information for characterizing event frequencies. The registry record also does not report a statistical analysis that could support formal inference for these outcomes.

Overall, the available record supports a description of the study design, endpoint definition, and listed safety counts. It does not support a conclusion about the primary response result or a comparative treatment effect. Not having those results reported is different from observing no response or finding no effect.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a cohort-specific response proportion in a single-group phase 2 design. A response proportion can be straightforward to explain, but its interpretation still depends on the denominator, the confirmation rule, the follow-up window, and the treatment path. The registry record defines these features in part, while leaving the primary response counts and rates unreported.

The study also illustrates why a cohort label should not be confused with a control group. Cohort A received IMM-101 with nivolumab. Cohort B could change to IMM-101 with ipilimumab after failing to respond and meeting criteria. This creates a treatment pathway tied to prior response and eligibility. Statistical comparisons across such groups would not automatically isolate treatment differences, even if outcome rates were available.

Enrollment is listed as 16, and the safety record lists one participant at risk in the IMM-101 and ipilimumab group. These counts make precision and the amount of information in each group important considerations. However, the record does not report confidence intervals for the primary outcome, so the precision of any response estimate cannot be assessed from these registry entries.

The record’s planning assumptions also help distinguish design calculations from findings. Planning illustrations using hypothetical assumptions are not observed power and cannot substitute for reported outcome estimates. In this case, the underlying primary response result is not reported in the registry information available for analysis. The key statistical lesson is to separate endpoint definitions, planned calculations, observed outcomes, and causal comparisons rather than treating them as interchangeable.

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 most direct limitation for interpreting efficacy is that the registry record does not report the primary response counts, denominators, or rates. It therefore does not permit an assessment of the observed response frequency or its precision. Although the record defines best overall response using confirmed investigator-assessed RECIST 1.1 responses, the response result itself is unavailable in the registry information analyzed.

The study is single-group and has no randomized control. The cohort structure does not create a like-for-like comparison: cohort B participants could change treatment after failing to respond to IMM-101 with nivolumab and meeting criteria. Any comparison between treatment groups would be affected by this conditional treatment path, and the record does not report an analysis that accounts for it.

The record lists enrollment as 16, but does not report cohort-specific enrollment or the primary endpoint denominators. The safety figures list one participant at risk in the IMM-101 and ipilimumab group, which limits the information available for describing that group. The registry record does not report baseline characteristics, the extent of missing response assessments, or how missing or unevaluable outcomes were handled.

Masking is listed as none. The record states that investigators determined response according to RECIST 1.1, but does not provide further information about assessment procedures or independent review. A statistical analysis plan, multiplicity handling, confidence intervals, and detailed outcome analyses are not reported in the registry record. These gaps limit independent assessment of analysis choices and uncertainty. They do not establish that any particular bias occurred, but they constrain what can be concluded from the registry entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of IMM-101 in Combination With Checkpoint Inhibitor Therapy in Advanced Melanoma — NCT03711188.
• Registry record last updated 2024-04-29; status last verified 2023-11.
• Results first posted 2024-04-29.
• 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

NCT03711188 is a completed phase 2, single-group study of IMM-101 with checkpoint inhibitor therapy in advanced melanoma, sponsored by Immodulon Therapeutics Ltd. The study start date is 2018-10-04, the primary completion date is 2021-12-02, and enrollment is listed as 16.

Cohort A received IMM-101 with nivolumab. Eligible cohort B participants who failed to respond to that combination had the option to change treatment on study to IMM-101 with ipilimumab. The primary endpoint was overall response rate, based on confirmed complete or partial responses as best overall response, divided by the intent-to-treat population in each cohort. The registry record does not report the response result or a statistical analysis.

Listed secondary outcomes include best overall response, progression-free survival, overall survival, and overall survival at one year. Safety counts are reported by treatment group, but the groups do not provide a randomized comparison.