Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer (NCT04958785), a randomized phase 2 study. The primary outcome is Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a Phase 2 randomized trial with no masking and a sequential model. The registry record lists 92 participants enrolled and a terminated status. The recorded start date is 2021-12-14, and the primary completion date is 2024-10-08. The reason for termination is not reported in the registry record.

The design contained safety run-in and Phase 2 cohorts. Safety Run-in Cohort 1 evaluated magrolimab with nab-paclitaxel or paclitaxel; its posted primary endpoint results are for the magrolimab and nab-paclitaxel group. Phase 2 Cohort 1 compared magrolimab with nab-paclitaxel or paclitaxel against nab-paclitaxel or paclitaxel alone, with progression-free survival by investigator assessment as the stated Phase 2 objective. The posted secondary efficacy result for this cohort is confirmed objective response rate by investigator assessment.

Cohort 2 evaluated magrolimab with sacituzumab govitecan. Its Phase 2 objective was confirmed objective response rate by investigator assessment, while safety run-in and Phase 2 Cohort 2 also had progression-free survival among the listed secondary outcomes. The primary endpoint, however, was dose-limiting toxicity in the two safety run-in cohorts, with different assessment windows: up to 28 days for Cohort 1 and up to 21 days for Cohort 2.

Because the registry describes a sequential structure and includes a safety run-in, the trial addressed both combination safety and later cohort-specific efficacy questions. The registry record does not report details of the sequence rules, allocation procedures, or any adaptations. It also does not report the reason for termination, so the termination status alone cannot establish why the study ended.

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: 129 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT-Evaluable Analysis Set included all participants who meet 1 of the following criteria: * Participant experienced a DLT at any time after initiation of the first infusion of magrolimab. * Participant did not experience a DLT and completed at least 3 infusions of magrolimab (28-day cycle), and at least 2 doses of nab-paclitaxel or paclitaxel (Safety Run-in Cohort 1 (SRiC1)), at least 2 infusions of magrolimab (21-day cycle), and at least 2 infusions of sacituzumab govitecan (SRiC2).

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: Participants in the Intent-To-Treat (ITT) Analysis Set (Phase 2 Cohort 1) and modified Intent-To-Treat (mITT) Analysis Set (Safety Run-in Cohort 1 and Cohort 2) were analyzed. * The ITT Analysis Set included all participants who were randomized in the Phase 2 Cohort 1. * The mITT Analysis Set included all enrolled participants who took at least 1 dose of study drug in Safety Run-in Cohort 1 and Cohort 2.

6. Primary Endpoint

The registry lists the primary outcome as Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs), measured over First dose date up to 28 days (Cohort 1) and up to 21 days (Cohort 2).

The primary endpoint was the percentage of participants in Safety Run-in Cohorts 1 and 2 experiencing dose-limiting toxicities (DLTs). A DLT was defined through specified serious toxicity criteria, including qualifying hematologic toxicity, events meeting Hy’s Law criteria, and qualifying Grade 3 or higher nonhematologic toxicity judged at least possibly related to magrolimab by the investigator. The assessment period began on the first dose date and extended up to 28 days for Cohort 1 and up to 21 days for Cohort 2.

As a percentage endpoint, the measure describes how often participants in the defined safety groups met the DLT criteria during their assessment windows. Safety run-ins commonly serve a dose-finding and tolerability role in a trial, and this study description specifically states that the run-in objective included evaluating safety, tolerability, and the recommended Phase 2 dose. That general context does not establish what dose decision was made; the recommended dose outcome is not reported in the registry record.

The posted result was 0.0% in each of the two safety run-in groups, with group sizes of 6.0 and 13.0. These findings refer to DLTs as defined for this endpoint and within its specified time windows. They do not summarize every adverse event or establish that participants had no other safety events.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: percentages and group sizes. A percentage endpoint expresses the share of participants meeting a defined event criterion. Its interpretation depends on the event definition, the participants included in the analysis, and the observation window. For the primary DLT endpoint, the registry specifies the event criteria and separate time windows for Cohort 1 and Cohort 2. The posted percentages are 0.0% in groups of 6.0 and 13.0 participants. With small groups, estimates are especially sensitive to individual outcomes, and a zero observed percentage does not imply that the underlying risk is precisely zero.

The registry describes a DLT-evaluable analysis set and gives partial eligibility criteria: participants qualified if they experienced a DLT after the first magrolimab infusion, or did not experience a DLT and completed at least 3 infusions in a 28-day cycle. The remainder of the eligibility description is not reported in the registry record. The endpoint result should therefore be understood in the context of the stated analysis set, not assumed to represent every enrolled participant.

How should the response estimates be read?

General: A confidence interval describes a range of values compatible with the data under the assumptions of the statistical procedure. It conveys precision, not the probability that a particular treatment effect is true. For confirmed objective response, the reported group estimates were 35.7% and 21.4%, with 95% confidence intervals of 12.8% to 64.9% and 4.7% to 50.8%. Their width reflects limited precision in these groups of 14.0 participants each. The registry does not identify the confidence-interval calculation method.

The comparative result includes a sponsor-reported odds ratio of 2.037, with a 95% confidence interval from 0.379 to 10.938. General: An odds ratio compares the odds of an event between groups; it is not the same as a difference in percentages. Values around 1 indicate similar odds, while values on either side indicate different relative odds. Here, the confidence interval is broad and includes 1, so the reported estimate is compatible with a range of effects. The analysis method is not reported in the registry record, and a p-value for this reported odds ratio is also not reported.

A separate simple, unadjusted recalculation from the posted summary statistics gives p = 0.403. A p-value measures how incompatible the observed data are with a specified null model under the test assumptions; it does not measure the size or importance of an effect. This recalculation is not an adjusted sponsor analysis and does not replace the reported odds ratio. The registry does not identify a p-value attached to the reported odds ratio.

What are planning illustrations?

General: Sample-size planning asks how many participants might be needed to detect a prespecified effect under stated assumptions. It is not a retrospective measure of how likely the completed trial was to detect an effect, and it is not observed power. The planning illustrations for the Cohort 1 response comparison use the observed effect or stated fractions of that effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. They give participants per arm for 80% and 90% power. The illustrations list 156 and 209 participants per arm for planning for 100% of the observed effect; 288 and 385 for 75%; and 670 and 897 for 50%.

These calculations are illustrations based on the observed response difference, not the trial’s own design justification. The registry record does not report the original sample-size justification or the assumptions used to plan enrollment. The small analyzed groups mean the observed effect used in these illustrations is itself uncertain, so the planning figures should not be read as a forecast of what a future trial would require.

General: multiplicity and unadjusted analyses. When several endpoints or comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed independently. Adjustment procedures can address this issue, but whether an adjustment was planned or applied is not reported in the registry record. Consequently, the unadjusted recalculation and secondary findings are best treated as exploratory evidence rather than definitive confirmatory tests.

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("Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxe", "Safety Run-in Cohort 2: Magrolimab + Sacituzumab G")
n      <- c(6, 13)
events <- c(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  Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxe  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Safety Run-in Cohort 2: Magrolimab + Sacituzumab G  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcomes across two cohorts, including efficacy, survival, safety, drug concentration, and antidrug antibody measures. It does not report whether a hierarchy of endpoints was prespecified, whether any statistical adjustment for multiple testing was planned, or which analyses were intended to be confirmatory. Without this information, secondary comparisons should be interpreted cautiously: assessing numerous outcomes can increase the chance of an apparently notable result arising by chance.

The reported odds ratio for confirmed objective response has a confidence interval, but its p-value is not reported in the registry record. A separate unadjusted recalculation gives p = 0.403. This result does not account for other outcomes or comparisons, and it should not be interpreted as a multiplicity-adjusted test.

The registry describes a DLT-evaluable analysis set, but the available population description is incomplete. Full criteria for that set are not reported in the registry record. The analysis populations for the posted secondary response outcome and other secondary endpoints are also not reported in the registry record. The record does not describe how missing outcome assessments were handled, whether participants with incomplete follow-up were excluded, or whether any imputation method was used.

These missing details matter because the population analyzed and the handling of missing data can affect both estimates and their uncertainty. The posted results should therefore be read as registry-reported findings for the stated outcomes, without assuming a particular missing-data procedure or multiplicity plan. The reason for termination and whether it affected completion of planned analyses are not 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: febrile neutropenia (23.1%), tachycardia (12.5%), vomiting (12.5%), breast abscess (12.5%), covid-19 (12.5%).

The primary safety endpoint counted dose-limiting toxicities meeting specified criteria during the run-in assessment windows. The posted result was 0.0% in Safety Run-in Cohort 1, with 6.0 participants, and 0.0% in Safety Run-in Cohort 2, with 13.0 participants. These values concern DLTs, not every adverse event.

The adverse-event summary uses separate groups and reports participants at risk, participants affected by serious events, participants affected by other events, and deaths. For example, in the Safety Run-in Cohort 1 group, 8 participants were at risk for serious events and 5 were affected; the same group lists 8 at risk and 8 affected for other events, with 2 deaths. These safety-group denominators do not always match the primary DLT group sizes. The registry record does not explain the difference, so the figures should not be combined or treated as if they describe identical analysis sets.

The most frequent listed serious terms include febrile neutropenia at 23.1%, followed by several terms at 12.5%. Such percentages describe reported serious-event terms, not an overall estimate of treatment effect or a direct comparison between groups. Death counts are reported by group, but their causes and relationship to treatment are not reported in the registry record. Serious adverse-event counts should be interpreted separately from DLT results.

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

The primary endpoint indicates that no participants in the two posted safety run-in groups were recorded as experiencing a DLT under the registry’s definition during the designated observation periods. It does not establish that there were no safety concerns, because the broader adverse-event summaries include serious events, other events, and deaths. The relatively small run-in groups also limit the precision of a zero observed DLT percentage.

The Cohort 1 response estimates describe confirmed objective responses in the two Phase 2 arms. Their confidence intervals are wide, and the reported odds ratio is also imprecise. The available comparison does not support a precise estimate of the difference between the groups. It should not be interpreted as definitive evidence that one regimen is better or worse.

These outcomes answer different questions. DLTs address a defined early safety endpoint in safety run-in cohorts; response rate addresses tumor response in Phase 2 Cohort 1. Neither outcome alone resolves the other listed questions, such as progression-free survival, overall survival, response duration, laboratory abnormalities, or drug exposure. Most numerical results for those secondary outcomes are not reported in the registry record.

The trial is recorded as terminated, but the reason is not reported in the registry record. Termination status alone does not explain the outcome pattern, establish whether analyses were complete, or show why the study ended. Taken together, the posted findings are limited observations from particular cohorts and endpoints. They do not establish a general conclusion about the effects of the studied combinations.

14. Why This Trial Matters Statistically

This trial illustrates why safety and efficacy endpoints must be kept distinct. The primary endpoint was a defined DLT measure in safety run-in cohorts, whereas the Phase 2 Cohort 1 response comparison addressed an efficacy question in a different set of participants. A zero DLT percentage cannot stand in for the full safety profile, and a response estimate cannot answer the primary safety question.

It also demonstrates the importance of precision. The response comparison is based on 14.0 participants in each arm, and the confidence intervals are broad. Reporting the effect estimate alongside its interval makes the uncertainty visible rather than reducing interpretation to a single percentage. Likewise, small safety run-in groups mean a zero observed DLT percentage should not be mistaken for a precise estimate of underlying risk.

The study’s sequential structure makes the distinction between run-in and Phase 2 objectives especially relevant. Safety run-in information may inform dose selection, while Phase 2 cohorts pursue cohort-specific objectives. The registry description states these broad aims, but the dose recommendation and details of the sequence are not reported in the registry record.

Finally, the study record includes several secondary endpoints but does not report a multiplicity plan, complete analysis populations, or missing-data methods. These omissions constrain how strongly secondary patterns can be interpreted. The combination of a terminated status, small posted groups, and incomplete reporting makes careful separation of observed findings, uncertainty, and unreported details central to a statistical reading.

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 DLT results come from small safety run-in groups, and the registry record does not provide confidence intervals for those percentages. The DLT-evaluable population description is incomplete, making it difficult to assess precisely who contributed to the primary endpoint. The safety summaries list different numbers at risk than the corresponding posted DLT group sizes in some cases; the record does not explain those differences.

The posted Cohort 1 response comparison also involves small groups, with wide confidence intervals. The method used for the reported odds ratio is not identified, and no p-value for that analysis is reported. The unadjusted recalculation is not a replacement for the reported analysis and does not address multiplicity.

Although multiple secondary outcomes are listed, most quantitative results are not reported in the registry record. The analysis populations, missing-data handling, multiplicity approach, and original sample-size justification are not reported. The status is terminated, but the reason and its effect on planned follow-up or analyses are not reported. These gaps limit assessment of how complete or representative the posted results are, and restrict conclusions to the endpoints and groups with reported data.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer — NCT04958785.
• Registry record last updated 2025-11-04; status last verified 2025-10.
• Results first posted 2025-10-03.
• 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

NCT04958785 is a Phase 2 randomized study of magrolimab combinations in participants with unresectable, locally advanced or metastatic triple-negative breast cancer. The study included safety run-in cohorts and Phase 2 cohorts, with a chemotherapy-alone comparator in Phase 2 Cohort 1. The registry lists 92 enrolled participants and a terminated status.

The primary endpoint was the percentage experiencing DLTs in Safety Run-in Cohorts 1 and 2. The posted results were 0.0% in groups of 6.0 and 13.0 participants. The Phase 2 Cohort 1 confirmed response estimates were 35.7% and 21.4%, with broad confidence intervals. The registry record does not report the reason for termination, the multiplicity plan, complete analysis-population definitions, or missing-data methods.