Oral SM-88 in Patients With Metastatic HR+/HER2- Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral SM-88 in Patients With Metastatic HR+/HER2- Breast Cancer (NCT04720664), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The clinical question is therefore descriptive: what objective response was recorded in this group receiving SM-88 with the three conditioning agents? The study’s stated purpose was to determine efficacy using objective response rate, while secondary outcomes included duration of response, progression-free survival, clinical benefit rate at or beyond 24 weeks, and treatment-related adverse events. The record lists these outcomes but does not provide results for them in the registry record for this analysis.

A single-group result can describe what was observed among enrolled participants, but it cannot by itself separate treatment effects from the course of disease, participant selection, assessment procedures, or other influences. That distinction matters especially for a small study. The registry record gives an enrollment of 11 and reports no response on the first assessment; it does not provide a comparison group or an inferential analysis that would establish how the observed result relates to outcomes under another approach.

3. Trial Design

This was a phase II, single-group, open-label study of oral SM-88 used with methoxsalen, phenytoin, and sirolimus in metastatic HR+/HER2- breast cancer. The registry identifies Georgetown University as sponsor. Allocation is recorded as not applicable, masking as none, and the study model as single group. These design features mean that the posted outcome is an observation in one treated group, rather than a contrast between randomly allocated groups.

The registry lists enrollment of 11. The recorded start date is 2021-09-22, and the primary completion date is 2023-02-10. The study status is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain why the study ended or whether the planned conduct changed.

SM-88 is the named intervention, and the arm description specifies that it was taken with methoxsalen, phenytoin, and sirolimus. Because these agents were used together, the response result describes the regimen as recorded; it cannot identify the separate contribution of SM-88 or any conditioning agent. The record does not list a concurrent untreated group or a separate active comparator.

The primary outcome was objective response rate, assessed every 8 weeks until progression, with an average timeframe of 8 weeks stated in the registry. The response definition used RECIST v1.1 for target lesions assessed by CT or MRI. Secondary outcomes were duration of response, progression-free survival, clinical benefit rate at or beyond 24 weeks, and incidence of treatment-related adverse events. The record lists five outcome measures and no analysis rows. Detailed protocol procedures, the sample-size justification, any interim analysis plan, and the statistical analysis plan are not reported in the registry record.

Open-label conduct means the record does not describe masking of participants or study personnel. That is a design characteristic, not evidence that outcome assessments were or were not influenced by awareness of treatment. The registry states the imaging methods and response criteria, but does not report additional assessment safeguards. Interpretation should therefore stay close to the registered design and the posted result.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: No patients responded to treatment on the first assessment.

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 Objective Response Rate (ORR), measured over Every 8 weeks until progression (an average of 8 weeks).

The primary endpoint was objective response rate, expressed as the percentage of patients with a complete response or partial response. The registry defines complete response as disappearance of all target lesions, with any pathological lymph nodes, whether target or non-target, reduced to less than 10 mm in short axis. A partial response requires at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum as reference. Assessments were specified every 8 weeks until progression, with an average of 8 weeks stated, and target lesions were assessed by CT or MRI under RECIST v1.1.

Objective response is used as a binary outcome: each assessed participant either meets the response definition or does not. Reporting a percentage expresses the frequency of response in the group, rather than the amount of change for every participant. In a single-group study, that percentage is descriptive; without a comparator, it does not estimate a difference between treatment strategies.

The registry’s primary outcome description says no patients responded at the first assessment. That statement should be read at the timepoint it names. The record does not provide a later response result in the registry record, nor does it provide a confidence interval or a sponsor-reported inferential estimate. The definition is specific to tumor measurements and does not encompass all possible clinical changes. It is also distinct from the listed secondary outcomes, such as duration of response, progression-free survival, clinical benefit rate, and safety.

General: an objective response endpoint can provide a standardized way to classify tumor shrinkage using prespecified measurement criteria. The value of that standardization depends on consistent assessments and clear reporting of the analysis population and timepoints. Those additional details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary outcome count?

Objective response rate classifies participants according to whether they meet a defined response threshold. In this study, complete and partial response were defined by RECIST v1.1, with target lesions assessed by CT or MRI. Complete response required disappearance of target lesions and a reduction of pathological lymph nodes to less than 10 mm in short axis. Partial response required at least a 30% decrease in the sum of target-lesion diameters relative to baseline. The registry gives the outcome unit as percentage of patients.

General: a binary outcome turns each participant’s assessment into one of two categories for the endpoint: response or no response. The percentage summarizes how often the response category occurred in the analyzed group. It does not describe the distribution of every participant’s tumor measurements or other outcomes. The registry states that no patients responded at the first assessment, but does not provide a response estimate for later assessments in the registry record for this analysis.

What does a confidence interval add?

General: an estimate from a study is subject to sampling variation. A confidence interval expresses uncertainty around an estimate under the assumptions of a statistical method. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. An interval does not resolve design limitations such as the absence of a comparison group, nor does it account automatically for unreported missing data or measurement problems.

No confidence interval for the primary response result is reported in the registry record. Consequently, the observed statement should not be extended into a precise estimate of the response rate in a wider population. The enrollment of 11 also means the result is based on a small group, so individual classifications have a strong influence on any group summary.

Why does the single-group design matter?

General: a randomized comparison can estimate differences between groups when allocation and analysis support that interpretation. A single-group study has no concurrent group to represent the outcome that might have occurred under an alternative condition. Here, allocation is not applicable and the model is single group. The posted result can describe the enrolled group, but it cannot provide a randomized comparison or separate the contribution of SM-88 from the three conditioning agents used with it.

Open-label conduct means masking was none. General: masking can reduce the influence of knowledge about assigned treatment on some aspects of care, reporting, and assessment. The registry record does not describe masking, because it records none; it does specify imaging and response criteria. It does not report additional safeguards or adjudication procedures. This should be treated as an information limitation, not as evidence that a particular assessment was biased.

What can be inferred from the analysis information?

The registry lists five outcome measures and no analysis rows. It does not report a p-value, interval estimate, adjusted model, or detailed analysis population for the primary endpoint in the registry record. General: statistical tests and models depend on an explicit analysis plan, including the outcome definition, population, treatment of missing observations, and timing of assessments. Without those details, a reader should not assume which method was used.

For binary outcomes, a statistical analysis may compare a proportion with a reference value or compare proportions across groups, but those approaches answer different questions. This study has no comparison arm in the record, and no reference-value test is reported. No significance test should be reconstructed from the response statement alone. A descriptive result and an inferential result are not interchangeable.

How should the planning illustrations be understood?

General: sample-size planning asks how many participants a future study might need under specified assumptions about an effect, significance level, allocation, and statistical approximation. Such planning outputs are hypothetical design illustrations. They are not observed power, and they do not change the information contained in the enrolled group’s result. The stated planning assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the planning convention is total number of events using Schoenfeld; for other outcomes, it is participants per arm.

These assumptions do not describe the actual study design, which was single group. The registry does not report the trial’s own sample-size justification. The planning assumptions therefore should not be mistaken for the protocol’s rationale, an analysis of observed power, or evidence that a two-arm study was conducted. No specific planning output is reported in the registry record for this analysis.

General: over-dispersion is relevant when observed variability exceeds what a model assumes. It can affect standard errors and the precision of estimates in settings where a count or rate model is used. The primary endpoint is described as a percentage, and the registry does not report an over-dispersion assessment or a model requiring such an adjustment. No claim about over-dispersion is warranted for this result.

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("Oral SM-88")
n      <- c(11)
events <- c(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  Oral SM-88  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome, objective response rate, and secondary outcomes of duration of response, progression-free survival, clinical benefit rate at or beyond 24 weeks, and incidence of treatment-related adverse events. It lists five outcome measures overall and no analysis rows. The registry entries available for this analysis do not include results for the secondary outcomes or a detailed statistical analysis plan.

Multiplicity arises when several outcomes, timepoints, subgroups, or statistical tests are examined. General: if many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of tests. The registry record does not report whether any multiplicity adjustment or hierarchy was planned. It is therefore not possible to say how the secondary outcomes were intended to support confirmatory conclusions.

The record does not report how missing assessments were handled, what analysis population was used for the primary outcome, or whether participants who discontinued or lacked an assessment were included in a particular way. These details matter for a response endpoint because a percentage depends on the set of participants represented in its denominator. The enrollment count alone does not establish the denominator used for every outcome or assessment.

The record also does not report whether there were interim analyses, how follow-up was summarized after termination, or whether all planned assessments were completed. Those matters should not be inferred from the listed assessment schedule or the study status. The first-assessment response statement can be described as written, but fuller interpretation would require the analysis population, missing-data handling, and outcome-specific results. Each of these details is 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: infections and infestations - other, specify (9.1%), dizziness (9.1%).

The safety fields list an Oral SM-88 group with 11 at risk for serious adverse events and 2 in the serious adverse-event affected count. The other adverse-event fields list 11 at risk and 10 affected. The registry also reports 1 death. These are separate posted counts; the record does not explain overlap among categories, timing, or whether the death was related to treatment.

The listed top serious adverse-event terms are “Infections and infestations - Other, specify” at 9.1% and “Dizziness” at 9.1%. The registry does not provide further detail about these terms in the registry record for this analysis. They should not be interpreted as a complete description of all events or as evidence about cause.

General: adverse-event counts describe events or affected participants according to the registry’s reporting fields. A count among a treated group is not a comparative risk estimate when there is no control group. Counts can also represent different kinds of information: a participant may experience more than one event, and categories may overlap. The registry record does not specify the overlap or event-level details, so the counts should not be added together or read as mutually exclusive categories.

The listed safety information supports a narrow description of what was posted. It does not establish whether an event was caused by SM-88, the conditioning agents, the underlying disease, or another factor. The reason for termination is also not reported in the registry record and should not be inferred from the safety counts.

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

The primary outcome statement is that no patients responded to treatment on the first assessment. It applies to the endpoint as defined by RECIST v1.1 and to the assessment time named in the registry record. It is a descriptive observation in a study with enrollment of 11, not an estimate of a treatment difference.

The study was single group and had no masking. Without a comparator, the result cannot show how the response experience differed from another treatment or from a control condition. Because SM-88 was taken with methoxsalen, phenytoin, and sirolimus, the result also cannot identify which part of the regimen accounts for any observed outcome. The registry does not report a confidence interval or a statistical test for the primary result, so its precision and inferential significance cannot be characterized from the posted information.

The first-assessment finding does not describe all possible later observations. The registry gives an assessment schedule of every 8 weeks until progression, with an average of 8 weeks, but the registry entries do not give later response results. Nor do they include results for the listed secondary endpoints. Missing results should not be interpreted as zero events or as evidence that a particular endpoint was not met.

The safety counts are also descriptive. They identify counts in the posted serious and other adverse-event fields and a death count, but do not establish causality or comparative safety. No conclusion about a treatment effect should be drawn from these figures alone.

General: a registry outcome can be useful for understanding what was planned and what was posted, while still leaving uncertainty about analysis methods, completeness, and precision. In this case, the record supports a narrow statement about the first response assessment and the listed safety counts. It does not, on its own, establish whether the regimen improves outcomes, how it compares with alternatives, or how reliably the observed findings would generalize beyond this enrolled group.

14. Why This Trial Matters Statistically

This trial matters statistically because its design and scale make the boundary between description and inference especially important. It is a phase II, single-group study with enrollment of 11. The primary outcome is a binary response classification, and the registry reports no patients responding at the first assessment. That is a concrete observation, but it does not carry the same meaning as a comparison between treatment groups.

With no comparator, an observed response percentage cannot isolate the effect of the regimen from other influences. The regimen included SM-88 with methoxsalen, phenytoin, and sirolimus, so the design also cannot attribute an outcome to one component. The open-label design and lack of masking are relevant context for interpreting assessments, while the record does not describe further safeguards.

The registry also illustrates why a result needs its analysis context. The primary outcome is defined, and the timepoint is stated, but the registry entries available for analysis do not include a confidence interval, a p-value, an analysis population, or missing-data methods. These details determine how precisely a result can be described and which participants contribute to it. The record lists secondary outcomes but does not provide their estimates in the information.

General: good statistical interpretation distinguishes the observed data from the broader claim a study might be intended to address. A result can be informative as a record of what was observed while remaining insufficient for causal or comparative conclusions. That distinction is particularly important when the group is small, the design is uncontrolled, and the registry record does not report the full analysis plan or results for all listed outcomes.

The posted findings therefore offer a focused example of how endpoint definitions, design, precision, and reporting completeness shape interpretation. The value is not in overstating what the result means, but in identifying exactly what it supports and what remains unresolved.

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.

Several limitations specific to this study affect interpretation. Enrollment was 11, and the design was single group. There was no comparator arm, allocation was not applicable, and masking was none. The primary response result is therefore descriptive and cannot estimate a difference from another treatment or identify a causal effect of the regimen.

The intervention combined oral SM-88 with methoxsalen, phenytoin, and sirolimus. Any group-level outcome applies to that combination as recorded; it cannot separate the contribution of the individual agents. The registry states that no patients responded on the first assessment, but does not report later response estimates in the registry record for this analysis. It also does not provide a confidence interval or p-value for the primary endpoint.

The study status is terminated. The reason for termination, the extent of follow-up after the primary completion date, and whether planned assessments were completed are not reported in the registry record. The record lists secondary endpoints, but their results are not included in the registry record. It also does not report the analysis population, handling of missing assessments, multiplicity procedures, interim analyses, or detailed statistical plan.

The safety reporting gives counts and two top serious adverse-event terms, but not event-level descriptions, timing, overlap, or causal attribution. The death count is posted without a stated relationship to treatment. These limitations mean the safety figures cannot be used as comparative estimates or as evidence of cause.

These gaps do not change the reported first-assessment finding, but they limit its precision, context, and generalizability. The registry record does not explain the sample-size justification, so enrollment should not be treated as evidence of an adequately powered design.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Oral SM-88 in Patients With Metastatic HR+/HER2- Breast Cancer — NCT04720664.
• Registry record last updated 2023-08-28; status last verified 2023-03.
• Results first posted 2023-08-28.
• 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

The registry record describes NCT04720664, OASIS, a phase II, open-label, single-group study of oral SM-88 with methoxsalen, phenytoin, and sirolimus for metastatic HR+/HER2- breast cancer. Georgetown University is listed as sponsor. Enrollment was 11; the study started on 2021-09-22, had primary completion on 2023-02-10, and is listed as terminated.

The primary outcome was objective response rate by RECIST v1.1, assessed every 8 weeks until progression, with an average of 8 weeks noted. The registry states that no patients responded at the first assessment. Secondary outcomes include duration of response, progression-free survival, clinical benefit rate at or beyond 24 weeks, and treatment-related adverse events.

The safety fields list 2 in the serious adverse-event affected count, 10 in the other adverse-event affected count, and 1 death, with 11 at risk in each adverse-event field. The reason for termination, primary-outcome confidence interval, detailed analysis population, missing-data approach, and secondary-outcome estimates are not reported in the registry record.