To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (NCT03544281), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs), Treatment A.

2. Clinical Question

3. Trial Design

NCT03544281, also identified as DREAMM-6, was a Phase I/II, open-label study with dose escalation and expansion. It evaluated belantamab mafodotin with Len/Dex in Arm A and with Bor/Dex in Arm B among participants with relapsed/refractory multiple myeloma. Allocation was non-randomized, masking was none, and the study model was sequential. These features describe a study intended to examine safety, tolerability and clinical activity across regimens and dose schedules, rather than a randomized comparison between treatment arms.

The registry lists enrollment of 153 participants and a completed status. The recorded study start was 2018-09-20, and primary completion was 2023-02-28. The registry record describes multiple belantamab mafodotin doses and schedules within the arms. In Arm A, the listed schedules include single and split doses. Arm B also includes multiple dose levels and schedules. Consequently, an arm label alone does not represent a single uniform exposure across all study participants.

The treatment duration also differed by regimen. Participants receiving Treatment A could continue combination treatment until progressive disease, intolerable adverse events, consent withdrawal, death or end of study. Participants receiving Treatment B could receive combination therapy for up to 8 cycles, then continue belantamab mafodotin monotherapy until one of the listed stopping events. These planned treatment pathways are relevant when interpreting exposure and safety summaries.

Because treatment allocation was not randomized, differences across arms or dose groups can reflect participant selection, dose and schedule, treatment duration, or other factors as well as the regimens themselves. The registry record does not report a randomized control group or a protocol-based head-to-head comparison. It also does not report the rationale for the planned enrollment or a formal sample-size justification.

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 study consisted of two phases - Main Study Phase (Day 1 to Month 53) and Post Analysis Continued Treatment (PACT) Phase (From Month 53 up to Month 65, which marks the completion of the PACT Phase for all participants). In PACT phase those participants still benefiting from drug continued to receive study drug until discontinued or withdrawn from study.

Only the first 6 of 22 groups are shown.

Main Study Phase

Reasons for not completing this period:

PACT Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT-evaluable population included participants who received at least 1 full dose of belantamab mafodotin and at least 75% of planned doses of Len/Dex by the end of Cycle 1 (Day 28). As pre-specified in protocol, only specified treatment arms were planned to be analyzed for DLTs.

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: All treated population included all participants who received at least one dose of study treatment.

Only the first 6 of 13 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs), Treatment A, measured over Up to 28 days.

The primary endpoint is the number of participants with dose-limiting toxicities in Treatment A, assessed over up to 28 days. A DLT is defined as an adverse event judged by the investigator to be clinically relevant, attributed to study therapy during the 28-day DLT period, and meeting at least one listed criterion. These include specified severe febrile neutropenia, thrombocytopenia with significant bleeding, certain laboratory abnormalities, non-hematologic toxicity that does not resolve with supportive treatment, Grade 4 corneal adverse events, and specified organ toxicity.

A DLT count is used in early-phase dose evaluation because it focuses attention on clinically important toxicities during a defined assessment period. It is a count of participants meeting the criteria, not a measure of all adverse events, their duration, or their severity beyond the endpoint definition. The registry record specifies a DLT-evaluable population: participants had to receive at least 1 full dose of belantamab mafodotin and at least 75% of planned Len/Dex doses by the end of Cycle 1 (Day 28). It also states that only specified treatment arms were planned for DLT analysis.

The registry record does not report the observed DLT count, the number analyzed for this endpoint, or an uncertainty estimate. As a result, the endpoint definition can be described, but its observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: each DLT-evaluable participant either met the endpoint definition during the specified assessment period or did not. The registry describes the endpoint as a number of participants with DLTs, so the natural summary is a count within the eligible group. A count needs its denominator for interpretation. Without the number of participants assessed, the count alone would not describe the observed proportion; in this record, neither the primary count nor the endpoint denominator is reported in the registry record.

What does a confidence interval express?

As a general statistical concept, a confidence interval describes the uncertainty around an estimate under a specified analysis method. For a binary endpoint, an interval around an estimated event proportion can convey how compatible the data are with a range of underlying event rates. It does not remove design limitations, and it does not establish that a treatment caused an observed rate. No confidence interval for the primary endpoint is reported in the registry record.

Why does the study design matter?

In a randomized trial, random allocation can help balance measured and unmeasured participant characteristics between groups, making a planned comparison easier to interpret. This study was non-randomized and sequential. Treatment groups therefore should not be assumed to be exchangeable. Differences in observed safety counts could arise from dose, schedule, background regimen, participant characteristics or time in treatment, among other possible factors. The registry record does not report an adjusted comparative analysis that addresses such differences.

Open-label status means masking was none. For a participant-level event such as a DLT, the endpoint definition includes investigator judgment about clinical relevance and attribution to study therapy. Lack of masking can matter when judgments depend on clinical assessment. The registry record defines the criteria but does not report independent blinded review or other adjudication procedures, so such procedures are not reported in the registry record.

How should the DLT population be understood?

The primary endpoint is not described as applying to every enrolled participant. The registry defines the DLT-evaluable population by treatment received and dosing during Cycle 1 (Day 28): at least 1 full dose of belantamab mafodotin and at least 75% of planned Len/Dex doses. It also says that only specified treatment arms were planned for DLT analysis. These restrictions define who can contribute to the endpoint according to the registry description. The number of participants meeting the criteria, the handling of participants who did not meet them and any protocol deviations are not reported in the registry record.

Restricting an endpoint population can be appropriate for a dose-limiting toxicity assessment when the outcome is intended to reflect exposure during a defined period. At the same time, the resulting count applies to the specified evaluable population, not automatically to all enrolled participants. This distinction matters when comparing the primary endpoint with broader safety summaries that include participants across phases and regimens.

What does over-dispersion mean for counts?

As a general statistical concept, over-dispersion occurs when variation in count data is greater than expected under a simple model. It can make model-based standard errors too small if the model assumes less variability than the data exhibit. Whether over-dispersion is relevant depends on the outcome and analysis model. The primary endpoint is a participant count, but the registry record does not report a fitted count model, a dispersion estimate or an analysis plan from which to assess this issue.

For a binary outcome, statistical methods may instead model the probability of an event, with uncertainty depending on the number of eligible participants and the observed event count. No such model, estimate or inferential test is reported in the registry record. Therefore, no inferential result should be inferred from the endpoint definition or from the existence of the study.

How do planning illustrations differ from trial results?

Any sample-size illustration based on an observed effect is a planning exercise, not an observed trial outcome and not observed power. Its result depends on assumptions about significance level, allocation, an assumed fraction of an effect and the statistical approximation. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation and a normal approximation; the effect to detect is a stated fraction of the observed effect. These assumptions describe the illustration, not necessarily the trial's design. The registry record does not report the trial's own sample-size justification or statistical design rationale.

More broadly, a planning sample size estimates what might be required under stated assumptions. It does not show that a study had a particular probability of detecting an effect after its results are known. The registry record does not report a power calculation as part of the trial analysis. It lists 0 analyses, so no inferential analysis can be attributed to the registry record.

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("Main Study Phase: Belantamab Mafodotin 1.9mg/kg SI", "Main Study Phase: Belantamab Mafodotin 2.5mg/kg SP", "Main Study Phase: Belantamab Mafodotin 2.5mg/kg SI")
n      <- c(3, 4, 6)
events <- c(0, 0, 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  Main Study Phase: Belantamab Mafodotin 1.9mg/kg SI  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Main Study Phase: Belantamab Mafodotin 2.5mg/kg SP  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Main Study Phase: Belantamab Mafodotin 2.5mg/kg SI  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 84 outcome measures, including the primary DLT endpoint and secondary pharmacokinetic outcomes. When a study assesses many outcomes, the chance of at least one apparently notable finding can increase if each is tested separately. As a general statistical concept, multiplicity procedures can control that risk, but they need to be specified in relation to the analysis plan. The registry record does not report a multiplicity adjustment, a hierarchy of confirmatory outcomes or a complete statistical analysis plan.

Missing data handling is also not reported in the registry record. This includes how participants who discontinue, miss doses, lack an assessment or are not DLT-evaluable were handled in analyses. The stated DLT-evaluable criteria identify a population but do not describe a missing-data method or establish how many participants met those criteria.

The record distinguishes the planned DLT-evaluable population from the total enrollment and says only specified treatment arms were planned for DLT analysis. The exact arms included, the analysis denominator and any exclusions are not reported in the registry record. No imputation method, sensitivity analysis or per-protocol comparison is reported.

These omissions limit the ability to assess selection into the endpoint population and the influence of missing observations. They also prevent a reader from reproducing the planned inferential analysis or determining whether reported findings, if any, were adjusted for multiple outcomes. The registry lists 0 analyses, and no statistical analysis results for the primary endpoint are reported in the registry 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 (50.0%), influenza (50.0%), nodular regenerative hyperplasia (33.3%), pneumonia (25.0%), non-cardiac chest pain (25.0%).

The safety summaries are organized by study phase and belantamab mafodotin dose and schedule, with Len/Dex or Bor/Dex as the background regimen. In the Main Study Phase, for example, the record reports 6 participants with serious adverse events among 12 at risk for the 1.9mg/kg STRETCH plus Len/Dex group, and 13 among 18 for the 2.5 mg/kg SINGLE plus Bor/Dex group. In the PACT Phase, the 1.9mg/kg STRETCH plus Len/Dex group has 1 participant with a serious adverse event among 3 at risk. These are descriptive group counts, not adjusted comparisons.

The registry also lists other adverse event figures and deaths separately. The number of participants at risk and the number affected are group-specific; they should not be combined across groups without a defined analysis. The listed serious adverse event terms include COVID-19 and Influenza at 50.0%, Nodular regenerative hyperplasia at 33.3%, and Pneumonia, Non-cardiac chest pain and Vertigo at 25.0%. The denominator and calculation basis for these term percentages are not reported in the registry record. Differences in group size, dose, schedule, treatment exposure and phase warrant caution when reading across groups.

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

The registry record describes a study designed to evaluate safety, tolerability and clinical activity of belantamab mafodotin in combination with Len/Dex or Bor/Dex. It provides the primary endpoint definition, eligibility criteria for the DLT-evaluable population, study design and group-specific safety summaries. Those details help define what was intended to be assessed and the populations to which descriptive safety counts refer.

However, the registry record does not report the result for the primary DLT endpoint. It does not give the number of DLT-evaluable participants, the count with DLTs or an estimate of uncertainty. The record therefore cannot establish the observed DLT frequency or how precisely it was estimated. The total enrollment of 153 does not substitute for the DLT denominator.

The serious adverse event summaries are not a randomized treatment comparison. Groups differ by phase, background regimen, belantamab mafodotin dose and schedule, and potentially treatment exposure. Because allocation was non-randomized, observed differences cannot be interpreted as effects caused by the regimens. The listed counts remain useful as descriptive safety information, but do not resolve comparative safety or clinical activity.

The study's stated objective includes clinical activity, yet the registry record does not provide results for that objective in the information recorded. A listed outcome or treatment plan is not itself a result. No conclusion that the treatment works or does not work follows from these registry entries. The appropriate interpretation is limited to the design and safety information that the record actually reports, with the principal endpoint result and its precision remaining unreported in the registry record.

14. Why This Trial Matters Statistically

This study raises several statistical issues common to early-phase combination trials. Its Phase I/II, dose-escalation and expansion structure includes multiple dose levels and administration schedules across two background regimens. The primary DLT endpoint is therefore tied to a defined early assessment period and an evaluable population, rather than simply to total enrollment. Clear denominators and endpoint results are essential for understanding such a safety summary, but they are not reported in the registry record.

The non-randomized sequential design is also central to interpretation. It can describe experience across regimens and schedules, but it does not create a randomized comparison. Group differences may reflect the sequence and selection of participants as well as dose, schedule or background treatment. Statistical adjustment cannot automatically eliminate these design concerns, and an adjusted analysis is not reported in the registry record.

In addition, the record lists many outcomes, including pharmacokinetic measures, while listing 0 analyses. This illustrates why outcome registration and outcome reporting are distinct: a long outcome list does not tell readers which analyses were conducted, how multiplicity was handled or how missing observations were addressed. Those details are not reported in the registry record.

For clinical researchers and biostatisticians, the main lesson is to separate what a study set out to measure from what its registry record reports. Here, the endpoint definition and safety group summaries are available, but the primary DLT result and its uncertainty are not. That distinction prevents descriptive data and planned objectives from being mistaken for evidence of a comparative treatment effect.

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.

Interpretation is limited by the absence of a reported primary endpoint result. The registry record does not give the DLT count, the number of participants evaluated for DLTs or an uncertainty estimate. Although enrollment is listed as 153, that total does not identify the endpoint denominator.

The design was non-randomized, unmasked and sequential. The treatment groups cannot be treated as randomized comparators, and differences across them may reflect dose, schedule, background regimen, phase or exposure as well as participant characteristics. The record does not report a controlled comparative analysis.

The study includes multiple dose and administration schedules, and its DLT endpoint applies to a specified evaluable population. The registry record does not report the number meeting those criteria, how participants outside that population were handled, or whether endpoint assessments underwent independent adjudication. Missing-data procedures and sensitivity analyses are not reported in the registry record.

The registry lists 84 outcome measures but 0 analyses. It does not report a full statistical analysis plan, multiplicity procedures, the trial's sample-size justification or results for the stated clinical activity objective. The denominator for the listed serious adverse event term percentages is also not reported in the registry record. These gaps limit assessment of precision, selective reporting, and the comparability of safety summaries across groups.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bortezomib Plus Dexamethasone (Arm B) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) — NCT03544281.
• Registry record last updated 2025-03-18; status last verified 2025-02.
• Results first posted 2024-05-20.
• 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

NCT03544281, DREAMM-6, was a completed, open-label Phase I/II, non-randomized, sequential study with dose escalation and expansion. It enrolled 153 participants with relapsed/refractory multiple myeloma and evaluated belantamab mafodotin with Len/Dex or Bor/Dex. The study began 2018-09-20, and primary completion was 2023-02-28.

The primary endpoint was the number of participants with DLTs in Treatment A over up to 28 days. The registry defines the DLT-evaluable population but does not report the endpoint count or its denominator. Group-specific serious adverse event and death counts are listed, alongside selected serious adverse event terms. The record lists 84 outcome measures and 0 analyses. The primary endpoint result, statistical analysis plan, missing-data methods and multiplicity procedures are not reported in the registry record.