Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants With RRMM: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants With RRMM (NCT07150104), a na phase 1, phase 2 study. The primary outcome is DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This is a phase I/II sub-study within the DREAMM5 master protocol. The record identifies the sub-study as evaluating belantamab mafodotin with nirogacestat, pomalidomide, and dexamethasone in participants with RRMM. The master protocol is identified as NCT04126200. The registry lists 14 participants enrolled, a start date of 2022-08-31, a primary completion date of 2025-04-17, and a status of active, not recruiting.

Although the official title describes the master protocol as randomized, this sub-study record lists allocation as NA and the model as single group. It lists one treatment group and no control arm. The record therefore does not describe a randomized, between-group comparison for this sub-study. Masking is listed as none, consistent with an open-label design. A comparator, allocation procedure, and masking procedure beyond these record entries are not reported in the registry record.

The stated primary purpose is to determine safety and tolerability and establish a recommended Phase 2 dose for combination treatment to explore in the cohort expansion phase. The registry identifies DE and CE phases in its outcome descriptions, but does not report an expanded definition of DE. It lists overall response rate and response categories for the DE Phase, clinical benefit rate and response categories for the CE Phase, and plasma concentration outcomes for both phases. These are listed outcomes, not reported findings.

The registry reports no outcome analysis results. In particular, the primary DLT count and the secondary efficacy and concentration results are not reported in the registry record. Without a control group or reported endpoint results, this record cannot provide a treatment-effect 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 results presented are based on the data cut-off date of 17 Apr 2025. Those participants still benefiting from study drug in the opinion of their treating physician continued to receive study drug in Post Analysis Continuation of Treatment (PACT) phase and their safety data will be provided within a year of study completion.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT Evaluable Population included participants in DE Phase who have received at least 80% of all components of the intended dose of treatment in cycle 1 and were followed up for a period of one cycle length or withdrawn within the first cycle due to an AE meeting the definition of a DLT.

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 DE Phase: Number of Participants With Dose Limiting Toxicities (DLTs), measured over Up to 28 days.

The primary endpoint is the number of participants with dose-limiting toxicities (DLTs) in the DE Phase. It is a count of participants, with an assessment timeframe of up to 28 days. The stated DLT Evaluable Population includes participants who received at least 80% of all components of the intended dose in cycle 1 and were followed for one cycle length, or who withdrew during the first cycle because of an adverse event meeting the DLT definition.

The registry’s criteria cover specified severe hematologic and non-hematologic toxicities, with listed exceptions, as well as tumor lysis syndrome, corneal toxicity, and certain organ-specific toxicities. Severity is graded using NCI CTCAE version 5.0. The definition’s specified exceptions matter: not every event in a broad category automatically qualifies as a DLT under the record’s criteria.

In early-phase dose evaluation, a DLT count is used to characterize treatment-limiting toxicity during a defined assessment period and to inform dose selection. That is a general explanation of the endpoint’s role; it does not establish how this study selected a dose or what decision followed. The registry record does not report the observed DLT count, the number of participants in the DLT Evaluable Population, or the resulting dose recommendation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Endpoint type and meaning. The primary endpoint is a count of participants with a DLT, rather than a continuous measurement or a time-to-event outcome. For a binary participant-level endpoint, each eligible participant is classified according to whether the event occurred within the defined assessment period. A count is the number classified with the event. A proportion can also describe the frequency, but requires a clearly specified denominator. In this record, the relevant denominator is the DLT Evaluable Population, whose membership depends on cycle 1 treatment exposure and follow-up. The registry does not report that population’s size or its DLT count.

Why define the evaluable population? The record requires participants to receive at least 80% of all components of the intended dose in cycle 1 and to complete one cycle length of follow-up, unless they withdraw within the first cycle because of an adverse event meeting the DLT definition. Such criteria establish which participants contribute to the primary endpoint assessment. General statistical considerations include the possibility that exclusions based on treatment exposure or follow-up can affect how representative an endpoint estimate is of everyone enrolled. The record does not report how many enrolled participants met the criteria, nor how any other exclusions or missing observations were handled.

What a confidence interval would convey. In general, a confidence interval describes uncertainty around an estimate under the assumptions of the statistical method used. For a binary outcome, an interval around an event proportion can indicate how imprecisely that proportion is estimated, particularly when the number of participants is limited. No confidence interval or DLT estimate is reported in the registry record, so the precision of the primary safety outcome cannot be assessed from this record.

Single-group interpretation. A single-group study can describe events observed among participants receiving the combination. Without a concurrent comparator, it does not directly estimate a difference between treatments. General statistical methods for comparing groups rely on observations from each group and on assumptions about how participants entered those groups. Here, the sub-study is listed as single group, with allocation marked NA. The master protocol’s randomized description does not create a randomized comparison within this sub-study record. No adjusted or unadjusted treatment comparison is reported.

Multiplicity. The record lists multiple secondary outcomes, including response measures and plasma concentrations. When a study evaluates many outcomes, general statistical practice may address the chance of false-positive findings across multiple tests through a prespecified testing strategy or other approach. A multiplicity adjustment, a testing hierarchy, and the statistical analysis plan are not reported in the registry record. No analysis results are posted from which to assess how multiple outcomes were interpreted.

Missing data and follow-up. In general, missing outcome information can affect estimates if the likelihood of being observed is related to the outcome. The primary endpoint’s evaluability definition addresses exposure and follow-up requirements, but the record does not report missing-data methods, imputation, sensitivity analyses, participant-level follow-up, or reasons for any missing endpoint data. The timeframe for the primary endpoint is up to 28 days; the record does not provide further detail about assessment timing for individual participants.

Planning versus observed evidence. Sample-size calculations are planning tools that depend on stated assumptions. They do not show that an effect was observed or establish the precision of an actual result. The sample-size illustration associated with this study uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect; its non-time-to-event outputs are participants per arm. Those assumptions describe a planning illustration, not the design of this single-group sub-study. Such calculations do not represent observed power, and they cannot supply a missing DLT result or create a valid comparator for this record.

What is not specified. The registry record does not report the statistical analysis plan, the method for estimating uncertainty for the primary endpoint, any interim analysis, or a sample-size justification for the sub-study. These details should not be inferred from the listed endpoints or the stated dose-selection purpose. The posted record gives the endpoint definition and population criteria, but not the analysis details or primary outcome result needed to reproduce or evaluate an estimate.

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("0.5 Milligram/Kilogram (mg/kg) Belantamab Mafodoti")
n      <- c(11)
events <- c(2)
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  0.5 Milligram/Kilogram (mg/kg) Belantamab Mafodoti  11  2  18.2  2.3  51.8  5.1  47.7  5.5  48.4

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary safety endpoint alongside secondary outcomes for response and plasma concentration. It names overall response rate for the DE Phase, clinical benefit rate for the CE Phase, response categories in both phases, and belantamab mafodotin concentration measures in both phases. The presence of several outcomes raises a general statistical consideration: repeated testing across multiple outcomes can increase the chance of at least one apparently notable finding. A prespecified hierarchy, adjustment, or other multiplicity strategy can clarify how results are interpreted, but the strategy used in this study is not reported in the registry record.

No outcome analysis results are reported. The record therefore does not provide estimates, uncertainty intervals, p-values, or analysis populations for the primary or secondary outcomes. It also does not report a statistical analysis plan or interim analyses. There is no basis in the registry record for assessing whether analyses were prespecified, whether all planned outcomes were analyzed, or how any multiple testing was handled.

The primary endpoint population is defined using treatment exposure and follow-up criteria. However, the number enrolled in that population, the handling of participants who did not meet its criteria, and methods for missing endpoint data are not reported in the registry record. The enrollment count should not be treated as the primary endpoint denominator unless the record states that the enrolled participants all met the evaluability criteria; it does not state that. These gaps limit assessment of both the endpoint estimate and its precision.

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 (42.9%), thrombocytopenia (14.3%), anaemia (7.1%), febrile neutropenia (7.1%), atrial fibrillation (7.1%).

The registry lists serious adverse event information for one treatment group. It reports 14 participants at risk and 12 affected by serious adverse events. For other adverse events, it reports 14 at risk and 14 affected. Three deaths are listed. These figures describe counts in the registry record; they are not a comparison with another group and do not by themselves establish cause or treatment attribution.

The listed serious adverse event terms include pneumonia at 42.9%, thrombocytopenia at 14.3%, anaemia at 7.1%, febrile neutropenia at 7.1%, atrial fibrillation at 7.1%, and myocardial infarction at 7.1%. The record does not report whether participants could contribute more than one event term, nor does it give event timing, duration, recurrence, severity by term, or attribution details. The terms should therefore be read as recorded safety categories, not as mutually exclusive participant groups unless specified elsewhere in the registry record.

Serious adverse events and DLTs are distinct classifications. The DLT endpoint uses criteria and a defined assessment timeframe, while the listed serious adverse event figures do not establish which events met those criteria. The primary DLT count is not reported in the registry record.

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

This record describes the purpose and design of an early-phase sub-study: to evaluate safety and tolerability of belantamab mafodotin with nirogacestat, pomalidomide, and dexamethasone, and to establish a recommended Phase 2 dose for further exploration in the cohort expansion phase. It identifies a single treatment group and a primary DLT endpoint assessed over up to 28 days. It also lists serious adverse event counts and terms among participants in that group.

The posted data do not report the number of DLTs, the DLT Evaluable Population size, or the dose recommendation. They also do not report secondary outcome results. Accordingly, the record does not show how frequently DLTs occurred under the endpoint definition, how precise an estimate would be, or what dose decision was made. The serious adverse event figures provide safety descriptions but cannot replace the missing primary endpoint result.

Because this is a single-group sub-study, the record does not compare the combination with another treatment or control. It cannot separate the contribution of each of the four drugs, estimate a comparative treatment effect, or establish how outcomes would have differed under another treatment. These limits apply even when the record lists event counts or rates: descriptive observations in one group are not a randomized comparison.

More generally, early-phase dose and safety information can inform further study, but the registry record alone does not establish the broader benefit-risk profile of a treatment. That general point is not a conclusion about the treatment in this study. It reflects the limited scope of the posted record: the primary result and several analysis details are not reported, and no comparator is included in this sub-study.

14. Why This Trial Matters Statistically

This study is statistically notable for the separation between its stated objective and what the registry record reports. The primary purpose concerns safety, tolerability, and dose selection, and the primary endpoint is explicitly defined as a participant count over a specified timeframe. Yet the primary DLT count and the size of its evaluable population are not reported. Without both, readers cannot assess the observed frequency of DLTs or the uncertainty around it.

The single-group structure is also important. The official title places the sub-study within a randomized master protocol, but this record lists allocation as NA and the model as single group. The sub-study’s observations can describe outcomes among participants receiving the combination, but they do not constitute a randomized treatment comparison. This distinction prevents readers from treating master-protocol language as evidence of a control group in the sub-study.

Finally, the record illustrates why endpoint definitions and analysis populations matter. The DLT Evaluable Population is determined by treatment exposure and follow-up, while enrollment alone does not establish how many participants contributed to that endpoint. The registry also lists several secondary outcome domains, but does not report their results or a multiplicity strategy. Together, these details show why a clear endpoint definition is necessary but not sufficient: interpretation also depends on the analysis population, results, uncertainty, and design context.

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 is the absence of the primary DLT result and the size of the DLT Evaluable Population in the registry record. Without those details, the primary safety endpoint cannot be interpreted quantitatively. The record also does not report a dose recommendation or the evidence used to select it, despite dose selection being part of the stated purpose.

The study is listed as single group, with allocation marked NA and no comparator. This limits interpretation to description of the treated group and prevents a direct comparison with another treatment. The open-label design is listed as having no masking; additional details about assessment procedures are not reported in the registry record.

The registry lists 14 enrolled participants, but does not state how many met the primary endpoint’s DLT Evaluable Population criteria. It also does not report how missing endpoint information or participants outside that population were handled. Safety terms and serious adverse event figures are listed, but event timing, duration, attribution, and whether terms overlap are not reported in the registry record.

Finally, the statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are not reported. The secondary outcome names do not supply their results. These limitations are specific to the posted record and should not be filled by assumptions about the master protocol or other studies.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants With RRMM — NCT07150104.
• Registry record last updated 2026-06-25; status last verified 2026-05.
• Results first posted 2026-06-25.
• 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

NCT07150104 is a phase I/II, open-label, single-group sub-study of belantamab mafodotin with nirogacestat, pomalidomide, and dexamethasone in participants with RRMM. The record lists 14 participants enrolled and identifies the primary endpoint as the number of participants with DLTs during up to 28 days in the DE Phase DLT Evaluable Population. The listed treatment group is labelled 0.5 mg/kg belantamab mafodotin with the other three drugs.

The registry lists serious adverse events affecting 12 of 14 participants, other adverse events affecting 14 of 14, and three deaths. It does not report the primary DLT count, the DLT Evaluable Population size, secondary outcome results, or a dose recommendation. With no comparator group, the sub-study record supports descriptive interpretation of the listed observations, not a treatment comparison.