Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer (NCT05041101), a na phase 1, phase 2 study. The primary outcome is Determine the Safety of Grapiprant and Eribulin Combination Treatment.

2. Clinical Question

The registry describes a Phase Ib/II investigation of a drug combination for metastatic inflammatory breast cancer. Its stated rationale is to assess safety and side effects and whether the combination can shrink tumors. The brief description characterizes grapiprant as an anti-inflammatory drug that may prevent tumor growth and eribulin as a drug that may block tumor-cell growth by stopping cell division. Those statements describe the rationale, not results of this study.

The enrollment was 6. Because the study was single-group and had no randomized control arm, its posted observations cannot by themselves distinguish changes associated with treatment from the natural course of disease, other care, or chance. The primary question is safety in the defined early treatment period; the registry also lists several disease-control and survival questions, but their results are not reported in the registry record.

3. Trial Design

The study is identified as a Phase Ib/II trial of grapiprant and eribulin for metastatic inflammatory breast cancer. M.D. Anderson Cancer Center is listed as the sponsor. The registry records a start date of 2021-12-21, a primary completion date of 2024-09-06, and a status of terminated. Enrollment was 6. Termination was requested by study supporter IKENA oncology during Phase 1b; the registry does not report additional detail about the decision.

The design is single-group, with allocation recorded as not applicable and masking recorded as none. Participants were assigned to treatment with grapiprant and eribulin mesylate as described in the registry. There is no separate control arm. The Phase Ib group descriptions include Dose Level 0, Dose Level -1, and Phase II, but the adverse-event record lists participants only for Dose Level 0. It lists zero at risk in the other dose-level groups. These entries do not support a controlled comparison between dose levels or between treatment and an untreated group.

The treatment schedule specifies oral grapiprant twice daily on days 1–21 and intravenous eribulin mesylate over 5 minutes on days 1 and 8. The described cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. The primary safety timeframe is up to 21 days from initial treatment, and the dose-limiting toxicity definition refers to events during Cycle 1 that were judged probable, possible, or definite as prespecified in the protocol.

The registry lists nine outcome measures and no analyses. Its secondary objectives include objective response rate, time to progression, duration of response, time to first response, progression-free survival, overall survival, and investigation of a predictive biomarker. The record does not report the protocol’s allocation rationale, a sample-size justification, interim analyses, or a detailed statistical analysis plan. It also does not report results for the listed secondary outcomes.

The single-group structure means the study can describe observations among participants who received the combination, but it cannot estimate a comparative treatment effect against a concurrent control. The small enrollment and termination during Phase 1b further limit what can be learned about the intended Phase II questions.

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: 8 patients were accrued and assessed for eligibility and 6 patients were assigned to the cohort.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Termination was requested by study supporter IKENA oncology during Phase 1b.

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: Termination was requested by study supporter IKENA oncology during Phase 1b.

6. Primary Endpoint

The registry lists the primary outcome as Determine the Safety of Grapiprant and Eribulin Combination Treatment, measured over Up to 21 days from the initial treatment.

The primary endpoint concerns safety of grapiprant and eribulin together. The registry describes dose-limiting toxicity as probable, possible, and definite events occurring during the first 21 days of treatment, designated Cycle 1. This early-treatment window is used to identify toxicities that may affect whether a regimen can be given as planned. In a Phase Ib study, such information is relevant to evaluating tolerability and dose levels, although the registry record does not state the protocol’s detailed dose-escalation or decision rules.

The outcome is described in terms of participants and a number, rather than a continuous measurement. For a binary event outcome, a participant is generally classified according to whether the event occurred within the specified window. Counts can then describe how many participants experienced the event, while an event proportion can describe its frequency in the group. The registry does not report the primary endpoint count or a corresponding estimate for dose-limiting toxicity, so neither can be inferred from the other adverse-event entries.

Safety endpoints are used because tolerability is a necessary part of evaluating a treatment regimen, especially early in development. They do not, by themselves, establish whether a treatment affects tumor response or survival. The registry lists these as separate objectives. Their results, as well as the primary endpoint result, are not reported in the registry record. The adverse-event information reported elsewhere in the record should therefore not be treated as a substitute for the specifically defined primary endpoint unless its timing and event classification match the protocol definition; that correspondence is not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study records outcomes among participants receiving the study regimen. It can describe observed events in that group and, when outcome data are available, estimate quantities such as an event proportion. It does not directly estimate a contrast against a concurrent untreated or active-treatment group. Without a comparison group, a change over time cannot be separated confidently from the natural course of illness, other care, measurement variation, or chance. This is a general limitation of uncontrolled designs, not a judgment about the treatment.

Here the registry identifies a single-group model, allocation as not applicable, and masking as none. The listed dose-level group labels do not amount to a randomized comparison. Adverse-event entries appear for Dose Level 0, while the other dose-level groups list zero participants at risk. A comparison between groups with no recorded participants would not provide a meaningful treatment contrast.

How should counts and proportions be understood?

The primary outcome is described as a number of participants, with the event concept being dose-limiting toxicity during Cycle 1. For a binary outcome, each participant contributes information about whether the specified event occurred in the defined period. A count is the number of participants meeting that definition. A proportion expresses that count relative to the number assessed. The registry does not provide the primary endpoint count or its analysis, so a primary-event proportion cannot be stated.

Counts are especially important to read alongside the denominator. In a small group, a single participant’s outcome can have a large effect on the observed proportion. Estimates from small samples are usually imprecise: a confidence interval communicates a range of values compatible with the data and the statistical model, rather than guaranteeing that the true value lies within that range. This is a general explanation; the registry record does not report a confidence interval for the primary endpoint.

Event terms can also overlap. One participant may experience multiple events, and one event may be categorized in more than one way. A list of event terms therefore should not be added up to infer the number of people affected. The registry’s listed serious-event terms and percentages should be read as reported categories, not as mutually exclusive participant groups unless the record explicitly establishes that they are exclusive. That information is not reported in the registry record.

Why do time windows and event definitions matter?

The primary safety timeframe is up to 21 days from initial treatment. Its description specifies probable, possible, and definite events in Cycle 1. An event outside that period, or an event that does not meet the protocol’s attribution definition, may not count toward this endpoint even if it appears in broader adverse-event reporting. Safety summaries can use different observation periods and definitions, so they are not interchangeable merely because both concern toxicity.

Consistent classification matters because an endpoint’s meaning depends on its operational definition: the event, timeframe, and rules for judging attribution. The record identifies the broad definition and timeframe, but does not report the endpoint result or the details needed to reconcile the primary endpoint with other event listings. Any such reconciliation would therefore be speculative.

What does the study’s analysis information establish?

The registry lists no analyses. It does not report a detailed statistical analysis plan, the analysis population for each outcome, missing-data methods, or an approach to repeated testing across the listed outcomes. It would be inappropriate to infer methods that are not described. The listed secondary objectives identify questions the study intended to investigate; they do not establish that each question was analyzed or that a result was observed.

For time-to-event outcomes such as time to progression, progression-free survival, and overall survival, a typical analysis accounts for the time each participant is followed and whether the event of interest has occurred. Participants without an observed event by the end of their available follow-up may be censored, meaning their event time is only known to exceed the time they were observed. This is a general explanation of the method. The registry record does not report event counts, follow-up summaries, censoring rules, or time-to-event analyses for this study.

For binary outcomes such as objective response, analysis requires a clear response definition, an assessment schedule, and a rule for participants whose response cannot be assessed. These details and the response results are not reported in the registry record. A response rate cannot be reconstructed from the study objectives or the adverse-event summaries.

How should sample-size illustrations be read?

Planning illustrations based on an observed effect are not the same as the trial’s original sample-size justification. They describe hypothetical sample sizes under stated assumptions. The stated assumptions for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For time-to-event outcomes, the illustrations concern a total number of events, while other outcomes are expressed as participants per arm. These are planning conventions, not observed trial outcomes.

Those assumptions do not describe this study’s design: the registry identifies a single group, not equal allocation between two randomized arms. Nor should a planning illustration be interpreted as observed power or as evidence that an effect was present. The registry record does not report the trial’s own sample-size justification. Because primary and secondary efficacy results are not reported, no observed effect estimate for those outcomes can be stated from the registry record.

Over-dispersion is a general concern when count outcomes vary more than a statistical model assumes; it can make standard errors too small if ignored. The primary endpoint is described as a participant count for an event, rather than a repeated count of events per participant, and the registry does not report an over-dispersion analysis. No conclusion about its relevance to the study’s actual analysis can be drawn from the 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("Phase Ib - Dose Level 0")
n      <- c(6)
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  Phase Ib - Dose Level 0  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple objectives: safety, objective response, time to progression, duration of response, time to first response, progression-free survival, overall survival, and predictive biomarkers. Considering multiple outcomes creates a multiplicity issue: the more statistical questions examined, the greater the general possibility of finding an apparently unusual result by chance if each is judged separately. This is a general statistical consideration, not evidence that such testing occurred in this study.

The registry lists no analyses and does not report a multiplicity adjustment, a hierarchy of confirmatory outcomes, or rules for interpreting the secondary outcomes. The primary objective is identified as safety, but the record does not state how the secondary objectives were to be prioritized or whether any were intended as confirmatory. The statistical plan for these questions is not reported in the registry record.

Missing-data handling and analysis populations are also not reported in the registry record. The record does not state how participants with incomplete outcome assessments, early discontinuation, or unavailable follow-up would be handled for each endpoint. Nor does it specify whether analyses were intended to include all enrolled participants, only treated participants, or another defined population. These omissions matter because the denominator and rules for including participants affect the interpretation of event and response estimates.

With enrollment of 6 and termination during Phase 1b, outcome availability could be particularly consequential, but the extent of missing data cannot be determined from the record. The registry does not give enough information to characterize missingness or assess whether it could bias results. No correction, imputation method, or sensitivity analysis should be assumed.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vomiting (16.7%), dyspnea (16.7%), lung infection (16.7%), fever (16.7%), back pain (16.7%).

For Phase Ib Dose Level 0, the adverse-event record lists 6 participants at risk, 4 with serious adverse events, 6 with other adverse events, and 6 deaths. It lists zero participants at risk and zero affected for the Dose Level -1 and Phase II groups. These are registry entries. The record does not provide further detail that would explain the circumstances or timing associated with the death count.

The serious-event terms listed are Vomiting, Dyspnea, Lung Infection, Fever, Back Pain, and Headache, each reported at 16.7%. The percentages should be read as the registry presents them. The record does not establish whether participants experienced more than one listed term, whether terms overlap, or how the percentages were derived. The terms are not necessarily separate groups of participants.

Serious adverse events and other adverse events are categories of reported events; seriousness does not itself establish that an event was caused by study treatment. Likewise, the deaths entry does not establish cause or treatment attribution. The registry record does not report the event-level narratives, attribution judgments, or relationship between the serious events and deaths. These figures should therefore be read as descriptive safety entries, not as a causal estimate or as the primary dose-limiting toxicity result.

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

The registry record establishes that a Phase Ib/II single-group study of grapiprant and eribulin was conducted for metastatic inflammatory breast cancer, with enrollment of 6, and that it was terminated during Phase 1b at the request of study supporter IKENA oncology. It describes the planned regimen and defines the primary safety question around dose-limiting toxicity during the first 21 days. The posted adverse-event entries provide limited descriptive information for Dose Level 0.

The record does not report the primary endpoint result. It also does not report results for the listed response, progression, survival, or biomarker objectives. Consequently, the registry information does not establish whether participants experienced tumor shrinkage, how long any response lasted, or how outcomes compared with another treatment. The study has no randomized control group, so even a reported change within the treated group would not by itself establish a comparative treatment effect.

The serious adverse-event and death entries require particular care. They document numbers and terms as recorded, but do not supply enough context to determine attribution, timing, overlap, or cause. They should not be interpreted as proof that the regimen caused a given event or death, nor should they be used as a substitute for the protocol-defined primary endpoint.

These limitations do not erase the descriptive information that is available. Rather, they define its scope: a small, terminated, early-phase single-group study with registry-reported safety entries and no posted primary or secondary outcome analyses. The record can identify what was intended and what was entered, but it cannot answer the study’s efficacy questions or support a comparative conclusion.

14. Why This Trial Matters Statistically

This trial illustrates why design and reporting details matter when interpreting early-phase clinical evidence. A safety question can be clinically and statistically distinct from questions about tumor response or survival. The registry defines its primary safety window and event attribution categories, while listing response and time-to-event objectives separately. Keeping those endpoints distinct prevents broad adverse-event summaries from being mistaken for the primary result.

The single-group design is also central to interpretation. Outcomes among treated participants can be described, but without a concurrent control group they cannot establish how outcomes differ from an alternative. The registry’s dose-level labels do not overcome that limitation: participants are recorded only in Dose Level 0, and the record does not supply a like-for-like comparison.

Small enrollment makes transparent denominators and uncertainty especially important. Counts can be informative about what was recorded, but a small group cannot precisely characterize uncommon outcomes or establish a stable event rate. The absence of a reported primary endpoint analysis, analysis populations, and missing-data methods further limits interpretability. Statistical methods cannot compensate for outcome information that is not reported.

The record also shows why trial status and completion context belong alongside outcome summaries. Termination was requested by the study supporter during Phase 1b, while the planned registry objectives extend to Phase II questions. Readers should distinguish intended objectives from completed analyses and avoid treating plans as findings. Together, these features make the study a useful example of how design, endpoint definition, sample size, and reporting completeness constrain the claims that can be drawn from a clinical trial record.

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 key limitation is the absence of a reported primary endpoint result. Although the registry defines dose-limiting toxicity during the first 21 days, it does not report how many participants met that definition or provide an estimate with uncertainty. The available adverse-event entries cannot be assumed to match that endpoint’s timeframe and attribution rules.

Enrollment was 6, and the study was terminated during Phase 1b. The registry does not report the supporter’s reason beyond stating that the termination was requested by IKENA oncology. It is therefore not possible to determine from the record whether the termination was related to safety, efficacy, feasibility, or another factor. The listed Phase II objectives should not be treated as evidence that Phase II analyses were completed.

The single-group design has no randomized comparator, and no masking was used. It cannot provide a controlled estimate of a treatment difference. The adverse-event information is reported for Dose Level 0, while the other listed groups have zero participants at risk; the record does not support comparisons across those groups.

Important details are not reported in the registry record, including the statistical analysis plan, sample-size justification, analysis populations, missing-data methods, and detailed event-level information. The serious events and deaths cannot be fully contextualized by timing or attribution. Results for objective response, progression, survival, and predictive biomarkers are also not reported. These gaps restrict both the safety interpretation and any assessment of tumor outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer — NCT05041101.
• Registry record last updated 2025-06-13; status last verified 2025-05.
• Results first posted 2025-06-13.
• 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

NCT05041101 is a Phase Ib/II single-group study of grapiprant and eribulin for metastatic inflammatory breast cancer, sponsored by M.D. Anderson Cancer Center. The registry records 6 enrolled participants, a start date of 2021-12-21, a primary completion date of 2024-09-06, and a terminated status. Termination was requested by study supporter IKENA oncology during Phase 1b.

The primary objective was safety, with dose-limiting toxicity defined for events during the first 21 days of treatment. The registry lists additional objectives covering response, progression, survival, and predictive biomarkers, but their results and the primary endpoint result are not reported in the registry record. Adverse-event entries list 4 participants with serious events, 6 with other events, and 6 deaths in Dose Level 0; the record does not provide enough detail to establish cause or treatment attribution. No randomized comparison is described.