BO-112 With Pembrolizumab in Unresectable Malignant Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BO-112 With Pembrolizumab in Unresectable Malignant Melanoma (NCT04570332), a na phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

The study was intended to assess preliminary anti-tumor activity and confirm safety for the combination in people whose melanoma had progressed on anti-PD-1-containing therapy. Its single-group design makes the response proportion descriptive of the treated population. Without a concurrent control group, the study cannot by itself establish how outcomes would differ under another treatment or without the combination. The registry record does not report a comparative treatment effect.

The primary endpoint counted complete and partial responses as overall responses. It was assessed from the first dose through the date of complete or partial response, with assessment described as occurring up to 2 years. The registry record does not report the number of participants who achieved each response category, the total number of responders, or the overall response percentage. Those missing results prevent a quantitative answer to the primary question from the registry information presented.

3. Trial Design

This was a phase 2, completed, single-arm, open-label study with an enrollment of 42. The registry record gives a start date of 2020-12-30 and a primary completion date of 2023-10-03. It describes an adaptive design, but the adaptation rules, any design changes, and whether any adaptation was implemented are not reported in the registry record.

All participants in the single arm were to receive intratumoral BO-112 with intravenous pembrolizumab. The arm description specifies BO-112 once weekly for the first 7 weeks and then every 3 weeks; pembrolizumab was administered every 3 weeks. The listed BO-112 dose is 1-2 mg at each administration. The registry record also lists tissue biopsies as a procedure. Details such as the timing and analysis of biopsies are not reported in the registry record.

The study was open label, meaning the record does not describe blinding of participants or study personnel. The primary response assessment was nevertheless assigned to independent radiological central review. The endpoint description specifies RECIST v1.0 and assessment by CT or MRI. Central review can provide a standardized radiological assessment, but the registry record does not report reviewer procedures, disagreement resolution, or whether other assessments were blinded.

The primary outcome was overall response rate, defined as the percentage of participants whose best overall response was complete response or partial response. Secondary outcomes listed in the record include adverse events and serious adverse events, disease control rate, duration of response, progression-free survival, and overall survival. A follow-up period or analysis method for each secondary outcome is not reported in the registry record.

Because there was no randomized comparator, allocation is not applicable and the participants do not form like-for-like treatment groups. The study can describe outcomes among those treated, but it cannot isolate the combination’s effect from other explanations such as the natural course of disease or differences among participants. The registry record does not report a control group, randomization procedure, or comparative analysis.

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

Analysis population for the primary outcome, as defined in the registry: Modified intent-to-treat population - patients with baseline and at least one post-baseline assessment. 2 patients from the ITT did not have post-baseline assessment and were excluded from mITT.

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.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate, measured over From the first dose of study treatment to the date of CR or PR assessed up to 2 years.

The primary endpoint was overall response rate: the percentage of participants whose best overall response was complete response or partial response. The record defines complete response as disappearance of all target lesions and partial response as at least a 30% decrease in the sum of the longest diameters of target lesions. The assessments were to use CT or MRI, RECIST v1.0, and independent radiological central review.

Response rate is a binary-outcome summary: each participant is classified according to whether the defined response occurred, and the result is expressed as a percentage of participants. It is used in a study of this kind to describe the frequency of observed tumor responses under treatment. It does not, by itself, describe how long a response lasts, whether disease remained controlled without meeting response criteria, or how the treated group’s outcomes compare with those under another approach.

The endpoint timeframe runs from the first dose of study treatment to the date of complete or partial response, assessed up to 2 years. The primary population was the modified intent-to-treat population, defined as participants with a baseline assessment and at least one post-baseline assessment. The record states that 2 participants from the intent-to-treat population lacked a post-baseline assessment and were excluded from the modified intent-to-treat population.

The response percentage, response counts, and 95% confidence interval are not reported in the registry record. Consequently, the endpoint definition is available, but the magnitude and precision of the observed response rate cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary response outcome expressed as a percentage. Each participant is classified by best overall response, with complete response or partial response counting toward overall response. This type of endpoint converts radiological assessments over time into a participant-level response classification. The registry record identifies the response criteria and assessment method, but does not report the statistical calculation used to produce the response percentage or its confidence interval.

What does the response definition capture?

RECIST v1.0 supplies the criteria named in the record for classifying changes in target lesions. Complete response means disappearance of all target lesions; partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions. The endpoint combines these categories. It therefore summarizes whether a participant met either response definition as their best overall response, rather than measuring the size or duration of response as a continuous quantity.

Independent central radiological review is specified for the primary assessment. In general, central review can apply a common assessment process across participants and may reduce dependence on local assessments. It does not remove all possible measurement uncertainty, and the record does not describe reviewer blinding, adjudication, or the handling of discordant assessments. Those procedures are not reported in the registry record.

What does a confidence interval tell the reader?

A confidence interval conveys uncertainty around an estimate. For a response percentage, it would help show how precisely the observed proportion is estimated from the analyzed participants. It does not describe the range of individual participant outcomes, and it does not establish a difference from a comparator. General statistical explanation: interval width depends on the amount of information in the data and on the method used to calculate the interval. The endpoint specifies a 95% confidence interval, but no interval bounds or response estimate are reported in the registry record.

The registry record calls the primary measure a percentage of participants and lists the dispersion as a 95% confidence interval. It does not state the specific interval procedure, whether any adjustment was used, or the handling of participants with unevaluable responses beyond the modified intent-to-treat definition. These method details should not be inferred from the endpoint label alone.

Why does the analysis population matter?

The primary endpoint population is the modified intent-to-treat population, defined as participants with a baseline assessment and at least one post-baseline assessment. The record says that 2 participants from the intent-to-treat population had no post-baseline assessment and were excluded. This definition means the primary endpoint analysis does not simply include every participant initially counted in the intent-to-treat population. Excluding participants without post-baseline assessment can affect the group represented by the response estimate; the direction and size of any effect cannot be determined without the missing outcome information and the analysis details.

General statistical explanation: missing outcome data can make an estimate less representative if the availability of assessments is related to participants’ outcomes. Different approaches to missingness rely on different assumptions. The registry record does not report imputation, sensitivity analyses, or other approaches to missing response assessments. It also does not report the modified intent-to-treat denominator or the amount of additional missing data.

How does the single-arm design affect inference?

A single-arm study measures outcomes in one treated group. Its response percentage can describe what occurred in that group, but there is no concurrent randomized group to estimate what would have happened under another treatment. General statistical principle: a single-group outcome is not a randomized treatment contrast. Differences in patient characteristics, disease course, assessment, and other factors cannot be controlled through a between-arm comparison when no comparator arm exists.

The study is described as adaptive, but the registry record does not report adaptation rules, interim analyses, stopping boundaries, or any changes to enrollment or analysis based on accumulating data. These details should not be assumed from the word “adaptive.” The sample-size assumptions for planning illustrations are not a substitute for the trial’s own statistical plan or justification. The registry record does not report the study’s sample-size justification, target power, or planned hypothesis-testing framework.

The record lists several secondary outcomes. General statistical explanation: when multiple outcomes or hypotheses are considered, the chance of at least one apparently unusual result can increase if each is assessed independently. Multiplicity procedures can address that issue, but the registry record does not report whether any such procedures were planned or applied. Numerical secondary-outcome results and analysis methods are also not reported in the registry record.

For safety, the registry reports participant counts for serious and other adverse events and lists selected serious-event terms. These are descriptive summaries, not a randomized comparison. General statistical explanation: event counts and percentages are most interpretable when the definitions, observation period, event attribution, and denominator are clear. The record does not provide all of those details, so the safety figures should be read as the registry’s reported counts rather than as a complete estimate of treatment-attributable risk.

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("Single Arm")
n      <- c(40)
events <- c(10)
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  Single Arm  40  10  25.0  12.7  41.2  14.2  40.2  14.2  40.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record names one primary outcome, overall response rate, and lists five secondary outcomes: number of participants with adverse events and serious adverse events, disease control rate, duration of response, progression-free survival, and overall survival. The record does not report a multiplicity adjustment or describe a hierarchy for testing these outcomes. Whether formal hypothesis tests were planned for the secondary outcomes is not reported in the registry record.

Multiplicity matters when several outcomes are examined. General statistical explanation: the more statistical questions considered, the greater the opportunity for a result to appear unusual by chance if each is judged separately. A prespecified testing strategy can help define how such findings should be interpreted. Without a reported strategy, secondary outcomes should be treated as descriptive rather than as confirmatory evidence unless further analysis details are available.

The primary analysis population was modified intent-to-treat: participants with a baseline assessment and at least one post-baseline assessment. The record says 2 participants from the intent-to-treat population lacked a post-baseline assessment and were excluded from this population. The modified intent-to-treat denominator is not reported in the registry record, and the primary response estimate is also absent.

How missing response data beyond that exclusion were handled is not reported in the registry record. Imputation, sensitivity analyses, and assumptions about missingness are not described. The record also does not report missing-data handling for the secondary outcomes. These omissions limit assessment of how fully the analyzed participants represent the enrolled group and how robust the outcome estimates would be to alternative missing-data assumptions.

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: general physical health deterioration (7.1%), pain in extremity (4.8%), haemorrhage intracranial (2.4%), disease progression (2.4%), device related infection (2.4%).

The safety summary records 15 of 42 participants with serious adverse events and 42 of 42 with other adverse events. It also records 7 deaths. These are counts for the single study arm; they are not comparisons between treatment groups. The registry record does not report an attribution assessment for the listed events, so the figures alone do not establish that an event was caused by study treatment.

The listed serious-event terms and recorded percentages are general physical health deterioration, 7.1%; pain in extremity, 4.8%; haemorrhage intracranial, 2.4%; disease progression, 2.4%; device related infection, 2.4%; and sepsis, 2.4%. The record does not state whether these terms are mutually exclusive, whether participants could contribute more than one term, or the event-level counts behind each percentage. They should therefore be read as the registry’s listed terms and percentages, not added together or treated as separate participant totals.

The record does not provide event timing, duration, severity grades, treatment relationship, or details for the 7 deaths. It also does not describe the observation period used for the safety summary. General statistical explanation: safety counts depend on event definitions, follow-up, and how repeated events or multiple events in one participant are represented. The summary supports a description of reported events in this group, but not a complete causal or comparative safety assessment.

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

The registry record describes a phase 2 study of BO-112 plus pembrolizumab in people with melanoma that progressed on anti-PD-1-based therapy. It specifies a primary endpoint based on complete or partial response, evaluated by independent radiological central review using RECIST v1.0. It also reports safety counts for the single study arm.

The primary response percentage and its 95% confidence interval are not reported in the registry record. This means the record does not show how many participants responded or how precisely the response proportion was estimated. The endpoint definition alone cannot answer the question of the observed response rate. The record also does not report numerical results for the listed secondary outcomes.

The design was single-arm and open label. General statistical interpretation: without a concurrent randomized comparator, outcomes in the treated group cannot determine what would have happened to similar participants under another treatment. Any observed response in such a study is descriptive and cannot, by itself, establish a causal treatment effect. Independent central review describes the primary assessment process, but it does not create a comparator or remove the limitations of the design.

The safety summary records serious and other adverse events and deaths, but does not report whether events were considered treatment-related or provide detailed event timing and follow-up. These counts should not be taken as proof of cause, nor can they be compared with another group in this study. The record’s safety information is therefore descriptive rather than comparative.

The study’s phase, design, population, treatment schedule, and outcome definitions give context for interpreting the registry entry. However, the missing primary estimate, interval, and analysis details leave important uncertainty about the observed results. No conclusion about comparative efficacy or treatment-attributable risk can be drawn from the registry record alone.

14. Why This Trial Matters Statistically

This study illustrates a recurring statistical distinction: an endpoint can be clearly defined even when its numerical result is not available in the registry record. Here, the primary outcome specifies the response categories, assessment criteria, imaging modalities, review process, analysis population, and assessment period. Yet the response percentage and its 95% confidence interval are not reported. A definition explains what was intended to be measured; it does not reveal what was observed.

The single-arm structure also matters. A response proportion can describe participants who received the combination, but does not provide the randomized comparison needed to estimate a treatment contrast. General statistical principle: a study’s ability to characterize an outcome and its ability to establish a causal effect are distinct. The open-label design and the use of independent radiological central review are also different features: independent review concerns outcome assessment, while absence of a control group limits comparative inference.

The analysis population raises another important interpretive issue. The endpoint uses a modified intent-to-treat population that excludes participants without a post-baseline assessment. The record states that 2 participants from the intent-to-treat population were excluded for this reason, but it does not give the modified population denominator or describe additional missing-data procedures. Readers therefore need to distinguish total enrollment from the group contributing to the primary endpoint.

Finally, the safety summary shows why event counts need context. The registry lists serious adverse events, other adverse events, deaths, and selected serious-event terms, but does not report event attribution or detailed timing. Those figures describe recorded events; they do not establish causation or support a comparison. Taken together, these features make transparent reporting of estimates, uncertainty, analysis populations, missing-data handling, and event definitions essential for statistical interpretation.

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 consequential limitation of the registry information is that the primary response estimate and its 95% confidence interval are not reported in the registry record. The endpoint can therefore be described, but its observed magnitude and precision cannot be evaluated. Numerical results for the secondary outcomes are also not reported in the registry record.

The study has a single arm and no concurrent comparator. It cannot provide a randomized comparison of the combination with another treatment. The record describes an open-label study, although the primary endpoint was assessed by independent radiological central review. Details of reviewer blinding, adjudication, or discordance handling are not reported in the registry record.

The endpoint uses a modified intent-to-treat population that requires a baseline and at least one post-baseline assessment. The record reports that 2 participants from the intent-to-treat population lacked a post-baseline assessment and were excluded, but does not report the modified population denominator. Further details about missing assessments, imputation, or sensitivity analyses are not reported in the registry record.

The registry describes the design as adaptive, but adaptation rules, interim analyses, and any resulting design changes are not reported. The sample-size justification and planned statistical testing procedures are also not reported in the registry record. Multiplicity handling for the primary and secondary outcomes is not described.

Safety interpretation is limited by the lack of reported event attribution, timing, and detailed follow-up information. The record lists 7 deaths but does not describe their causes or relationship to treatment. These limitations are specific to the information recorded and should not be filled by assumptions about the protocol or analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BO-112 With Pembrolizumab in Unresectable Malignant Melanoma — NCT04570332.
• Registry record last updated 2025-11-26; status last verified 2025-11.
• Results first posted 2025-11-26.
• 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 describes a completed phase 2, single-arm, open-label study with enrollment of 42 and an adaptive design. It evaluated intratumoral BO-112 with intravenous pembrolizumab in advanced and/or metastatic melanoma that had progressed on anti-PD-1-containing treatment. The primary endpoint was overall response rate, based on complete or partial response by independent radiological central review using RECIST v1.0.

The primary response percentage and 95% confidence interval are not reported in the registry record. The endpoint population required a baseline and at least one post-baseline assessment; 2 participants from the intent-to-treat population without a post-baseline assessment were excluded. The safety summary records 15 participants with serious adverse events, 42 with other adverse events, and 7 deaths. Event attribution and detailed analysis methods are not reported in the registry record.