INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Relapsed or Refractory Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Relapsed or Refractory Multiple Myeloma (NCT03837509), a randomized phase 1, phase 2 study. The primary outcome is Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE).

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel phase 1/2 study, with no masking reported. Its stated purpose was to evaluate the safety and antitumor activity of INCB001158 combined with subcutaneous daratumumab compared with subcutaneous daratumumab alone in participants with relapsed or refractory multiple myeloma. The registry lists total enrollment of 15 and identifies Incyte Corporation as the sponsor.

The registry describes three treatment approaches: INCB001158 plus daratumumab, daratumumab monotherapy followed by crossover to the combination after confirmed disease progression, and INCB001158 monotherapy followed by crossover to the combination after confirmed disease progression. The phase 1 primary endpoint results are reported separately for the 75 mg BID and 100 mg BID INCB001158 combination groups. The registry also lists phase 2 groups, including a combination group and the two monotherapy-and-crossover approaches.

The study start date is 2019-09-25, and the primary completion date is 2022-04-05. Its status is terminated. The reason for termination is not reported in the registry record. Nor does the registry record describe how randomization was implemented, how treatment assignment was concealed, or whether the study had planned stopping rules.

The overall trial description names a comparison with daratumumab alone, but the posted primary endpoint counts concern the two phase 1 combination groups. The design and the primary endpoint results therefore need to be kept distinct: a study can include several arms and phases while its posted primary outcome data cover only a subset of them. The registry does not report a direct primary-endpoint comparison between the combination and daratumumab monotherapy.

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.

Phase 1

Reasons for not completing this period:

Phase 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Population: all participants enrolled in the study who received at least 1 dose of study treatment (INCB001158 or daratumumab subcutaneous \[SC\]). Participants were to be analyzed according to the treatment they were assigned to.

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 Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), measured over up to 454 days.

The primary endpoint counts participants with at least one treatment-emergent adverse event, or TEAE, in phase 1. The registry defines a TEAE as an adverse event reported for the first time after the first dose of study treatment, or the worsening of an event that was already present. The stated timeframe is up to 454 days.

This is a binary participant-level outcome: each participant is classified according to whether an event occurred, and the reported result is a count of participants with an event. The phase 1 record reports 6 participants with a TEAE among 6 assigned to INCB001158 75 mg BID plus daratumumab, and 4 among 4 assigned to INCB001158 100 mg BID plus daratumumab.

Counting participants with any TEAE is a broad way to describe how many experienced at least one event during the specified observation period. It does not convey how many events each participant experienced, how severe each event was, or whether an event was judged related to study treatment. Separate adverse-event information may address some of those dimensions, but the primary endpoint alone does not.

The primary endpoint is a safety measure, not a measure of antitumor activity. Response, time to response, duration of response, progression-free survival, and minimal residual disease appear among the registry’s other outcomes. Their results are not part of the primary endpoint counts and should not be inferred from them.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary result is a binary outcome summarized as a participant count. For this type of endpoint, each participant contributes to the denominator for their group and is counted as having an event or not having an event. The registry reports the group sizes and event counts for the two phase 1 combination groups: 6 of 6 and 4 of 4 participants had at least one TEAE. These are observed counts, not estimates adjusted for other characteristics.

What does a count tell the reader?

A count directly describes how many participants met the endpoint definition in the observed group. It is straightforward to interpret, but it does not show how variable the underlying event rate might be across comparable groups of participants. General statistical principle: uncertainty around a proportion depends on both the observed proportion and the amount of information in the data. Small groups usually leave substantial uncertainty, even when the observed count is clear. A count should therefore not be mistaken for a precise estimate of what would occur in a larger population.

The primary endpoint is participant-level and records whether any qualifying TEAE occurred. It is not a count of the total number of events. A participant with one event and a participant with several events both contribute as a participant with an event for this endpoint. The registry’s definition also includes worsening of a pre-existing event after the first dose. That timing rule defines the endpoint but does not establish that the study treatment caused the event.

Why is there no comparative estimate?

The registry explicitly indicates that values are missing or not estimable for a two-arm comparison of this binary endpoint, and it reports no analyses. As a result, there is no posted comparative effect estimate, confidence interval, or p-value to interpret. General statistical principle: a confidence interval expresses the range of effect values compatible with the data under a stated method and assumptions. Without a reported interval, the precision of a comparative effect cannot be assessed from an interval estimate. The observed counts alone do not supply a substitute for a registered or sponsor-reported analysis.

The groups also differ in size, and the primary endpoint results are limited to phase 1 combination groups rather than including a posted daratumumab-only primary result. A direct comparison requires results for the groups being compared and a defined analysis. The overall study description cannot replace those missing elements. No adjustment method, model, or testing procedure for this endpoint is reported in the registry record.

How should planning illustrations be understood?

Any sample-size illustrations associated with an observed effect are planning exercises, not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. General statistical principle: a planning calculation asks how much information might be needed to detect a specified effect under assumed conditions. It does not change the actual number of participants enrolled, and it does not indicate the probability that the study’s result is true. The registry does not report that these assumptions were the trial’s original design assumptions or that they governed enrollment.

The registry record does not provide numeric sample-size illustration results in the posted trial details, so no planning estimate can be interpreted. It also does not report a sample-size justification for the trial. The enrollment of 15 is the reported study enrollment, not a statement about a target number or the adequacy of the study’s power.

What analysis details remain unknown?

The record identifies the primary endpoint population as enrolled participants who received at least one dose of study treatment, analyzed according to assigned treatment. This describes an important population rule, but does not give a complete statistical analysis plan. The registry does not report methods for handling missing primary endpoint data, the timing of data cutoffs for individual participants, or a model for the primary outcome. It does not report whether any interim analyses were planned or conducted. Those details should not be inferred from the randomized, open-label design or from the existence of multiple study phases.

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("Phase 1: INCB001158 75 mg BID + Daratumumab", "Phase 1: INCB001158 100 mg BID + Daratumumab")
n      <- c(6, 4)
events <- c(6, 4)
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  Phase 1: INCB001158 75 mg BID + Daratumumab  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase 1: INCB001158 100 mg BID + Daratumumab  4  4  100.0  39.8  100.0  51.0  100.0  47.8  99.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes across phase 1 and phase 2. These include response, time to response, duration of response, treatment-emergent adverse events, progression-free survival, and minimal residual disease. When a study examines multiple outcomes or makes multiple comparisons, the chance of at least one apparently unusual result can be affected by the number of statistical tests. General statistical principle: multiplicity procedures can address this issue, but the appropriate approach depends on the planned questions and analysis strategy.

A multiplicity adjustment or hierarchy for the outcomes is not reported in the registry record. Because the record reports zero analyses, there are no posted p-values or inferential results from which to assess how multiple testing was handled. The registry’s list of outcomes alone does not establish which were intended to be confirmatory, how they were prioritized, or whether any adjustment was planned.

The primary endpoint population is described as participants enrolled who received at least one dose of study treatment, analyzed according to assigned treatment. The record does not report how missing endpoint status was handled, whether any participants were excluded from that population, or whether missing observations occurred. A complete missing-data analysis cannot be reconstructed from the posted counts.

Information about interim analyses, stopping boundaries, and other prespecified statistical procedures is not reported in the registry record. These omissions do not prove that such procedures were absent; they mean that the registry record does not document them. The primary endpoint counts should therefore be read as descriptive posted results, without assuming unreported analysis choices.

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 (100.0%), fatigue (25.0%), pain (25.0%), atrial fibrillation (16.7%), condition aggravated (16.7%).

The broader adverse-event record reports 5 participants with serious adverse events among 15 at risk, 13 with other adverse events among 15 at risk, and 9 deaths. The phase-specific group counts are also listed: the phase 1 INCB001158 75 mg BID plus daratumumab group had 3 participants with serious adverse events among 6 at risk; the phase 1 100 mg BID combination group had 1 among 4. The phase 2 groups had 0 among 2, 1 among 1, and 0 among 2, respectively. These are counts, not comparative estimates.

The registry lists pneumonia at 100.0% among the serious adverse event terms, followed by fatigue and pain at 25.0% each, and atrial fibrillation, condition aggravated, and constipation at 16.7% each. The denominator underlying these term percentages is not described in the registry record, so the percentages should not be translated into participant counts or interpreted as group-specific risks.

The record also lists deaths by group, but does not state that the deaths were caused by study treatment. Serious adverse events, other adverse events, and deaths are distinct summaries and should not be conflated with the primary endpoint count of participants with any TEAE.

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

The posted primary endpoint counts show that all 6 participants in the phase 1 75 mg BID combination group and all 4 participants in the phase 1 100 mg BID combination group experienced at least one TEAE, as defined by the registry. This establishes what was recorded for these participants; it does not establish the frequency that would be expected in a broader population with the same condition or treatment.

The counts do not establish that the two dose groups differ, because no comparative analysis or uncertainty interval is reported. They also do not establish that INCB001158 plus daratumumab is safer or less safe than daratumumab alone. Although the study description includes a daratumumab-alone comparison, the posted primary endpoint results are only for two combination groups. A primary endpoint result for the monotherapy comparator is not reported in the registry record.

The endpoint captures whether a participant had at least one event, not the total number of events, the duration of events, or a full account of severity. The separate serious adverse event and other adverse event summaries provide additional counts, but do not by themselves identify causality. The timing-based TEAE definition is not equivalent to a determination that treatment caused an event.

The registry reports that the study was terminated, but does not report the reason. It also does not report a statistical analysis of antitumor activity outcomes in the registry record for this analysis. Consequently, no conclusion about response, disease control, or comparative efficacy follows from the primary safety counts.

General statistical principle: results from small groups can be especially imprecise, and observed counts can differ from the underlying risks that would be seen across a larger set of participants. The available data should therefore be interpreted as limited descriptive evidence about the enrolled participants, not as a definitive estimate of comparative safety or efficacy.

14. Why This Trial Matters Statistically

This trial raises several statistical interpretation issues that matter in early-phase clinical research. First, it combines phase 1 and phase 2 components and includes multiple treatment approaches, while the primary endpoint reported for analysis is a phase 1 safety count from two combination groups. Keeping the overall design separate from the subset of posted primary results prevents an apparent study-wide comparison from being mistaken for an analyzed comparison.

Second, the primary endpoint is a broad binary measure. It is useful for describing whether participants experienced any treatment-emergent event, but it does not describe event burden, severity, or attribution in detail. Reading it alongside, but not substituting it for, serious adverse event information helps clarify what each safety summary can and cannot answer.

Third, the small group sizes and the absence of a posted comparative estimate make precision central to interpretation. Counts can be accurately reported even when a comparative effect remains too uncertain or is not estimable in the registry. The record reports no analysis, so the descriptive findings should not be turned into a test of whether the groups differ.

Finally, the study’s terminated status, multiple outcomes, and crossover treatment descriptions make transparent reporting important. The registry does not state the termination reason, a multiplicity strategy, or a full statistical analysis plan. These are meaningful limits on reconstruction of the trial’s inferential framework, rather than details that can be safely filled in from general knowledge of phase 1/2 studies.

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 primary endpoint results cover two phase 1 combination groups and do not include a posted result for the daratumumab-only comparator. This prevents a direct reading of the primary safety endpoint as a comparison between the combination and monotherapy, despite the broader trial objective naming that comparison.

The group sizes for the primary results are small, and the registry reports no comparative analysis, confidence interval, or p-value. The endpoint is a participant count for any TEAE, so it does not show event frequency per participant, severity distribution, duration, or treatment attribution. The broader safety record adds serious adverse event and death counts, but does not state causality for deaths or provide enough detail to reinterpret the primary endpoint.

The registry is marked terminated, but the reason is not reported in the registry record. Details about the timing and rationale for termination are therefore unavailable. Although the study description includes crossover after confirmed disease progression for two monotherapy groups, the record does not provide enough analysis information to determine how crossover was incorporated into outcome analyses.

Methods for missing data, interim analyses, multiplicity, and the primary endpoint’s inferential analysis are not reported in the registry record. The stated population definition does not resolve those questions. The serious adverse event term percentages also lack a stated denominator in the registry record, limiting their interpretation as risks or counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Relapsed or Refractory Multiple Myeloma — NCT03837509.
• Registry record last updated 2025-11-04; status last verified 2025-10.
• Results first posted 2023-03-20.
• 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

NCT03837509 is a randomized, open-label, parallel phase 1/2 study sponsored by Incyte Corporation. It enrolled 15 participants with relapsed or refractory multiple myeloma and evaluated INCB001158 with subcutaneous daratumumab in a design that also included monotherapy and crossover groups. The registry lists a start date of 2019-09-25, primary completion on 2022-04-05, and a terminated status.

The primary phase 1 outcome was the number of participants with any TEAE, defined to include new events or worsening pre-existing events after the first dose. The posted counts were 6 of 6 in the 75 mg BID combination group and 4 of 4 in the 100 mg BID combination group. No comparative analysis is reported, and the reason for termination is not reported in the registry record.