MGC018 With or Without MGA012 in Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MGC018 With or Without MGA012 in Advanced Solid Tumors (NCT03729596), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03.

2. Clinical Question

3. Trial Design

NCT03729596 was a phase 1/2, first-in-human, open-label study of MGC018 alone and in combination with MGA012, according to its official title. The registry lists the study as non-randomized, unmasked, and sequential. These design features mean the listed cohorts were not allocated as randomized, concurrently controlled groups. Differences between their outcomes therefore cannot be interpreted as if they arose from a like-for-like randomized comparison.

The dose-escalation cohorts are listed at 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 3.0 mg/kg, and 4.0 mg/kg IV every 3 weeks. The expansion cohorts for metastatic castrate-resistant prostate cancer, non-small cell lung cancer, triple-negative breast cancer, melanoma, and squamous cell carcinoma of the head and neck are listed at 3.0 mg/kg IV every 3 weeks. The brief summary says participants could receive additional cycles for up to two years if they did not experience unacceptable toxicity or meet criteria for permanent discontinuation. It also describes survival follow-up for expansion participants every 3 months for 2 years following the last dose.

The registry lists enrollment of 143 and a terminated status. The study start date is 2018-11-21 and primary completion is listed as 2023-03-18. The specific reason for termination is not reported in the registry record. Nor are detailed enrollment targets by cohort, the sequence or rules for dose escalation, or the criteria used to select expansion doses reported in the registry record. The title refers to treatment with or without MGA012, but the intervention and arm descriptions do not specify a distinct MGA012 regimen or identify a control group.

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: Module B of the study was never initiated. There were no participants enrolled.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

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.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Adverse Events of Vobramitamab Duocarmazine as Assessed by CTCAE v4.03, measured over Throughout the study up to 24 months.

The primary endpoint counts participants with adverse events attributed to the study’s safety assessment. The registry specifies assessment using CTCAE v4.03 and describes adverse events and serious adverse events from study-drug administration through the End of Study visit. Its stated timeframe is throughout the study up to 24 months. This is a count outcome: it describes how many participants were recorded as affected, rather than the number of events each participant experienced or the time until an event.

Safety is a central outcome in an early-phase, first-in-human study because the study is evaluating tolerability as well as pharmacokinetics, pharmacodynamics, and preliminary antitumor activity. Counts of participants with adverse events can describe the safety experience observed in each cohort. Serious adverse events are an important subset to examine separately, while other adverse-event counts provide additional context.

These counts do not, by themselves, establish that the study drug caused an event. Nor do they indicate how severe every event was, how long it lasted, or whether participants had repeated events. The registry’s primary endpoint title refers to adverse events, while its description also says that serious adverse events were evaluated. Detailed endpoint rules for counting recurrent events, grading all events, or attributing causality are not reported in the registry record. The reported counts should therefore be read as the registry’s recorded participant counts, not as a complete account of each participant’s clinical course.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a sequential, non-randomized, open-label phase 1/2 study. That design is important when interpreting its statistical results. Random allocation can help balance known and unknown prognostic factors across treatment groups; without it, groups may differ for reasons unrelated to the intervention. Open-label status means masking was none. The record does not report a randomized control arm, and the listed cohorts should not be treated as equivalent comparison groups.

What does a participant count convey?

The primary outcome is a count of participants with adverse events. A participant count records whether a person was affected under the endpoint definition; it is not necessarily a count of every event experienced. The serious and other adverse-event figures are presented by cohort, alongside the number at risk. Those denominators matter because a count has meaning in relation to the participants whose outcomes were assessed. A raw count should not be compared across cohorts as though each cohort had the same size or the same participant characteristics.

General statistical explanation: for a binary outcome, a proportion can summarize the number of participants with an event relative to the number assessed. An uncertainty interval can show how imprecise an estimate may be, particularly when a group is small. No confidence intervals or inferential estimates for these event counts are reported in the registry record. No additional calculations should be inferred from the counts alone.

Why does the non-randomized design matter?

General statistical explanation: randomization supports causal comparisons by making treatment assignment independent of participant characteristics in expectation. In a non-randomized sequential study, dose and cohort assignment may be related to enrollment sequence, clinical characteristics, or study decisions. The registry record does not report enough detail to assess those relationships. Consequently, differences between the dose cohorts or disease expansions are descriptive rather than controlled estimates of treatment effects. The record also does not provide a comparator group against which to estimate what would have happened without the intervention.

The sequential structure is consistent with the listed dose-escalation and expansion cohorts, but detailed escalation rules, stopping boundaries, and decision procedures are not reported in the registry record. It would be inappropriate to infer a dose-selection algorithm or a particular safety threshold from the cohort list alone. Specific analyses of dose-response are not reported in the registry record.

How should the secondary outcomes be understood?

The listed secondary outcomes span different statistical types. Best overall response and objective response rate are categorical outcomes; progression-free survival, duration of response, and overall survival are time-to-event outcomes; PSA response outcomes concern prostate-specific antigen; and area under the curve is a pharmacokinetic measure. Each type requires outcome definitions and analysis methods suited to its measurement. For time-to-event outcomes, censoring can occur when a participant’s event time is not observed during follow-up. General statistical explanation: methods for these outcomes account for the timing of events and censoring, rather than treating every participant as if follow-up were identical. The specific analysis methods, censoring rules, and estimates are not reported in the registry record.

The registry lists 16 outcome measures and no analyses. The listed secondary outcomes identify what was intended for assessment, but their presence does not establish that results were collected or analyzed in a particular way. Definitions such as response criteria, the handling of unevaluable participants, and analysis populations are not reported in the registry record. The primary endpoint population is also not specified there.

What do planning illustrations mean?

General statistical explanation: a sample-size calculation describes the number of participants or events that a hypothetical design might require under stated assumptions. It is not a measure of the evidence actually observed in a completed study and should not be described as observed power. The planning illustrations associated with the posted material are based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events, while other outcomes use participants per arm. These are planning assumptions, not the trial’s own design justification. The registry’s prospective sample-size justification is not reported in the registry record.

Because the trial is non-randomized and does not list a like-for-like control comparison, planning an equal-allocation two-arm comparison from an observed effect does not turn the cohort data into a randomized comparison. Any such illustration is hypothetical and depends on its assumptions. It cannot establish the reliability of the trial’s observed results or substitute for a reported statistical analysis plan.

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 1", "Cohort 2", "Cohort 3", "Cohort 4", "Cohort 5", "mCRPC Expansion")
n      <- c(3, 6, 7, 7, 6, 41)
events <- c(3, 6, 7, 7, 6, 41)
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 1  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Cohort 2  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Cohort 3  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Cohort 4  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Cohort 5  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  mCRPC Expansion  41  41  100.0  91.4  100.0  91.4  100.0  91.6  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and multiple secondary outcomes, including response, survival, PSA, and pharmacokinetic measures. When many outcomes are assessed, the chance of seeing an apparently notable result by chance can increase. General statistical explanation: multiplicity procedures can control or describe this issue by adjusting how evidence is evaluated across several tests. Whether any such procedure was planned or used is not reported in the registry record. The registry lists no analyses, so adjusted or unadjusted inferential results are not available in the record.

Missing-data rules are not reported in the registry record. In particular, the record does not specify how participants with incomplete follow-up, unevaluable response, early discontinuation, or missing outcome measurements were handled. For time-to-event outcomes, censoring rules are not reported. The number of participants included in each outcome analysis and the definition of each analysis population are also not reported in the registry record. Enrollment of 143 does not establish that every enrolled participant contributed to every outcome.

The registry record does not report a statistical analysis plan, interim analyses, prespecified subgroup analyses, or a sample-size justification. These absences limit assessment of whether outcome definitions and analysis choices were set before results were known. They also mean the listed endpoints should not be assumed to have been tested using any particular model or missing-data approach. Without these details and outcome estimates with measures of uncertainty, the posted information supports descriptive interpretation of the recorded cohort counts, not a reconstruction of the planned inferential analysis.

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: pneumonia bacterial (33.3%), sepsis pasteurella (33.3%), pneumonitis (33.3%), pleural effusion (19.0%), thrombocytopenia (16.7%).

The registry reports serious adverse events by cohort as participants at risk and participants affected. For example, the dose-escalation Cohort 1 reports 1 affected participant of 3 at risk; the metastatic castrate-resistant prostate cancer expansion reports 23 of 41; and the squamous cell carcinoma of the head and neck expansion reports 5 of 13. The cohort-specific counts describe the recorded safety experience, not comparative risks established by randomization. The record also reports other adverse events for each cohort; all listed participants at risk are recorded as affected in those other-event counts.

Deaths are also listed by cohort, but the figures do not establish treatment causality. The record does not explain the relationship of each death to study treatment or provide detailed timing and circumstances. Serious-event terms listed with percentages include Pneumonia bacterial at 33.3%, Sepsis pasteurella at 33.3%, Pneumonitis at 33.3%, Pleural effusion at 19.0%, Thrombocytopenia at 16.7%, and Gastrointestinal inflammation at 16.7%. The denominator and calculation basis for these percentages are not reported in the registry record. They should be read as registry-listed term percentages, not as fully interpretable cohort-specific rates.

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

The posted information describes a non-randomized, open-label phase 1/2 study of vobramitamab duocarmazine in people with advanced solid tumors. It shows that the registry recorded adverse events, serious adverse events, and deaths across dose-escalation and disease-specific expansion cohorts. The counts and listed serious-event terms provide a descriptive account of what was recorded among participants at risk. The secondary outcome list also indicates that response, survival, PSA, and pharmacokinetic measures were part of the study’s outcome scope.

Those observations do not establish that an event was caused by the study drug, and cohort-to-cohort differences do not establish a dose effect or a difference between tumor types. There is no randomized, like-for-like control comparison in the registry design. The title refers to MGC018 with or without MGA012, but the registry’s arm and intervention descriptions do not give enough detail to identify a specific MGA012 regimen or comparator. The record therefore does not support a direct comparison of treatment with and without MGA012.

The registry information also does not provide inferential results, confidence intervals, or detailed analyses for the listed secondary outcomes. Statistical uncertainty and the effect of missing outcome data cannot be assessed from the reported counts alone. The terminated status is recorded, but the reason for termination and its impact on outcome completeness are not reported in the registry record. These limitations mean that the posted data characterize recorded outcomes in this study; they do not, by themselves, quantify a causal treatment effect or resolve how the intervention compares with an alternative.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between early-phase cohort description and controlled treatment comparison. Its dose-escalation and tumor-specific expansion structure can organize safety and exploratory outcome collection across different clinical groups. But the non-randomized, open-label design means the cohorts do not provide a like-for-like control comparison. A count observed in one cohort cannot be interpreted as the counterfactual outcome that would have occurred in the same participants under another treatment.

The primary safety outcome is a participant count, while the secondary outcomes include categorical, time-to-event, and pharmacokinetic measures. Those outcome types require different definitions and analysis approaches. The record lists the outcomes but does not report analysis details, missing-data methods, analysis populations, or inferential estimates. This makes the registry record useful for understanding the study’s stated scope and recorded safety counts, while limiting formal statistical evaluation of treatment effects and precision.

The contrast between a detailed list of study outcomes and the absence of reported analyses also highlights why outcome definitions and analysis plans matter. Without those details, readers cannot determine from the registry alone how repeated events, incomplete follow-up, or unevaluable outcomes were handled. The terminated status adds a further reason to avoid assuming that every planned outcome was fully collected or analyzed; the reason and consequences are not reported in the registry record. The central statistical lesson is to keep descriptive cohort findings separate from causal claims.

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 describes a non-randomized, open-label study with sequential cohorts rather than a randomized control comparison. Cohort counts may reflect differences in group size and participant mix, as well as differences in dose or tumor type. The record does not report enough detail to separate these influences. The title mentions study treatment with or without MGA012, but the intervention and arm descriptions do not specify an MGA012 regimen or provide details of a comparator group.

Detailed outcome definitions are limited in the registry record. It does not report the criteria used for response outcomes, the analysis rules for survival outcomes, or the handling of repeated adverse events. The primary endpoint population, analysis populations, and missing-data procedures are not reported. Nor are statistical models, confidence intervals, p-values, interim analyses, multiplicity procedures, or a prospective sample-size justification reported in the registry record. The registry lists no analyses.

The record gives a terminated status but does not report the reason for termination or whether it affected recruitment, follow-up, or outcome availability. Although enrollment is listed as 143, the number assessed for each endpoint is not specified in the information. The term-specific serious adverse-event percentages are listed without a reported denominator or calculation details. Death counts are not accompanied by causal attribution or detailed timing. These gaps limit assessment of precision, completeness, and causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MGC018 With or Without MGA012 in Advanced Solid Tumors — NCT03729596.
• Registry record last updated 2025-07-31; status last verified 2025-07.
• Results first posted 2025-07-31.
• 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

NCT03729596 is a phase 1/2, first-in-human, open-label, non-randomized sequential study of vobramitamab duocarmazine in advanced solid tumors. The registry lists dose-escalation cohorts and expansion cohorts for metastatic castrate-resistant prostate cancer, non-small cell lung cancer, triple-negative breast cancer, melanoma, and squamous cell carcinoma of the head and neck. The primary outcome counts participants with adverse events assessed using CTCAE v4.03. Enrollment is listed as 143, and the status is terminated.

The registry lists safety counts by cohort and a set of secondary response, survival, PSA, and pharmacokinetic outcomes. It does not report analyses, detailed analysis populations, missing-data methods, or a randomized control comparison. The reason for termination and the specific MGA012 regimen are not reported in the registry record. The available cohort counts should therefore be interpreted descriptively, rather than as evidence from a controlled causal comparison.