Ph1 Study of SL-172154 Administered Intratumorally in Subjects With Squamous Cell Carcinoma of the Head and Neck or Skin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ph1 Study of SL-172154 Administered Intratumorally in Subjects With Squamous Cell Carcinoma of the Head and Neck or Skin (NCT04502888), a na phase 1 study. The primary outcome is Incidence of All Treatment Emergent Adverse Events.

2. Clinical Question

3. Trial Design

This was a Phase 1, open-label, multicenter dose-escalation study of SL-172154 given by intratumoral injection. The listed conditions were cutaneous squamous cell carcinoma and squamous cell carcinoma of the head and neck. The registry lists sequential as the study model, no masking, and allocation as not applicable. It does not describe a randomized assignment or a concurrent control group.

The safety results list SL-172154 (0.003 mg) and SL-172154 (0.01 mg). The numbers at risk for the serious and other adverse-event summaries were 3 and 2, respectively. The registry lists enrollment as 5; these entries describe different aspects of the record and should not be used to infer unreported participant flow or analysis populations.

The registered primary outcome was incidence of all treatment-emergent adverse events. The outcome timeframe ran from Day 1 to 90 days after the last injection, described as an average of 6 weeks. Treatment could continue until disease progression or withdrawal of consent, with no maximum treatment duration stated. The study summary also describes safety, pharmacokinetics, antitumor activity, and pharmacodynamic effects as evaluation aims.

The study status is terminated. The registry lists a start date of 2020-09-17 and a primary completion date of 2022-04-08. A reason for termination, the dose-escalation decision rules, and the planned statistical analysis are not reported in the registry record.

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

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 Incidence of All Treatment Emergent Adverse Events, measured over From Day 1 to 90 days after last injection of SL-172154, an average of 6 weeks. SL-172154 administration continued until disease progression or withdrawal of consent; there was no maximum treatment duration..

The primary endpoint is the incidence of all treatment-emergent adverse events, expressed as the number of participants who experienced an event. It is a participant-level count: the endpoint description concerns whether participants had events, rather than the total number of event episodes. The registry record does not give the primary endpoint result by dose group.

The stated observation window begins on Day 1 and extends to 90 days after the last injection; the record describes this as an average of 6 weeks. The treatment period itself could continue until disease progression or withdrawal of consent, with no maximum duration. Thus, participants might have different lengths of treatment exposure, while follow-up after the last injection is specified in the endpoint timeframe.

In general, an adverse-event endpoint is used in an early-phase study to describe safety and tolerability during and after treatment exposure. A count of participants with events is easier to interpret than a count of event episodes when an individual may experience more than one event. It does not, by itself, establish that treatment caused an event. The record's primary endpoint title is broad; it does not report event severity, relatedness, or an overall participant count for this endpoint.

The serious and other adverse-event figures in the record provide safety information, but they do not substitute for a reported result for the full primary endpoint. The endpoint population and the handling of participants with incomplete follow-up are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: a participant either is or is not counted as having a treatment-emergent adverse event during the defined observation period. In general, binary outcomes can be reported as counts and proportions. For this record, the adverse-event group summaries give counts at risk and counts affected for serious and other events, but they do not report the complete primary endpoint result. No additional primary-endpoint estimate should be reconstructed from these separate safety categories.

In general, a confidence interval describes the statistical uncertainty around an estimated quantity. With sparse observations, the range of values compatible with the data can be wide, and estimates can change substantially when observations change. The registry record does not report confidence intervals for the safety summaries. The listed group sizes are small, so the counts are best read as a description of what was recorded in these groups rather than as precise estimates of event rates in a broader population.

In general, statistical tests assess whether observed data are compatible with a specified null model, given assumptions about the design and sampling process. A test does not correct a design limitation, establish causation, or show that groups were comparable. No inferential analyses are listed in the registry record. It does not report a statistical analysis plan, a prespecified comparison between doses, or a method for estimating uncertainty.

The dose groups arose in a sequential dose-escalation study, not a randomized comparison. In general, sequential dose cohorts may differ in the participants enrolled, treatment exposure, and the circumstances under which each dose was studied. Without random allocation or a concurrent control, a numerical contrast between cohorts is descriptive and may be confounded. The record does not report enough detail to assess cohort comparability or the rules used to move between dose levels.

The registry lists planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning illustrations, not observed power. The registry record does not report the statistical analysis that generated the observed effect used in the illustrations, and the listed assumptions do not establish that they were part of the trial's original design. The planned enrollment is 5, but the record does not report a sample-size justification. The actual planning illustration outputs are not reported in the registry record.

In general, planning calculations depend on the outcome type, the assumed effect, variability, significance level, allocation, and analysis method. A calculation based on a fraction of an observed effect is conditional on that effect estimate and does not show that the study had a particular probability of detecting an effect. Small or unstable estimates can make such planning values especially uncertain. Because no planning outputs or underlying observed effect are reported in the registry record, no conclusion about required future sample sizes can be drawn from the assumptions alone.

Over-dispersion is a general concern when binary outcomes vary more than a simple statistical model assumes. If it is present and not accounted for, standard errors may be too small and uncertainty may be understated. The registry record does not report an over-dispersion assessment or a model-based analysis. Given the small groups and absence of inferential analyses, there is no reported model result to evaluate on this point.

Multiplicity is the issue of interpreting results when many outcomes or comparisons are considered. The registry lists 15 outcome measures and 0 analyses. In general, considering multiple endpoints can increase the chance of finding an apparently notable result by chance if many unadjusted tests are performed. The record does not report that such tests were performed, nor does it describe a multiplicity adjustment. The number of registered outcomes alone is not evidence that any testing or adjustment occurred.

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("SL-172154 (0.003 mg)", "SL-172154 (0.01 mg)")
n      <- c(3, 2)
events <- c(3, 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  SL-172154 (0.003 mg)  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  SL-172154 (0.01 mg)  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 0 analyses. Its secondary outcomes include recommended Phase 2 dose, objective response rate, immunogenicity, and pharmacokinetic measures, including Cmax, Tmax, Cmin, AUC, and terminal elimination half-life. The record does not report results for these outcomes or an analysis plan identifying which outcomes were primary for inference beyond the stated adverse-event endpoint.

In general, testing or estimating many outcomes raises multiplicity concerns. If multiple tests are used to support confirmatory claims, an adjustment or a prespecified hierarchy can help control the interpretation of chance findings. The registry does not report a multiplicity strategy, and the absence of listed analyses does not show that a particular strategy was or was not used outside the registry entry.

Handling of missing data is not reported in the registry record. It does not describe how incomplete adverse-event follow-up, withdrawal, or missing outcome measurements were treated. The primary endpoint population is blank, and the analysis populations for the secondary outcomes are not reported. The counts at risk in the safety summaries should not be assumed to define every outcome's analysis population.

The record also does not report whether participants were analyzed according to any prespecified population definition, how exposure duration was considered, or how missing pharmacokinetic or response data were handled. Without these details, the extent to which missingness could affect the reported summaries cannot be assessed.

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: pharyngeal haemorrhage (50.0%), acute kidney injury (50.0%), hypercalcaemia (50.0%), hyponatraemia (50.0%).

For SL-172154 (0.003 mg), the registry reports 0 serious adverse events among 3 participants at risk and 3 participants with other adverse events among 3 at risk. For SL-172154 (0.01 mg), it reports 2 participants with serious adverse events among 2 at risk and 2 participants with other adverse events among 2 at risk. The record lists 0 deaths in the 0.003 mg group and 1 in the 0.01 mg group. These counts describe the registry entries; they do not establish that treatment caused the events or death.

The four serious adverse-event terms are each listed as 50.0%. The registry record does not report the denominator or dose-group context for those percentages, so they cannot be converted into counts or compared across groups. It also does not report event relatedness, severity beyond the serious classification, timing, or whether events overlapped within participants. Serious adverse events and other adverse events are separate categories in the posted summaries; the record does not give a complete account of all treatment-emergent events for the primary endpoint.

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

The posted data establish that the registry contains safety counts for two SL-172154 dose groups, including serious and other adverse events and deaths. They do not provide a complete numerical result for the primary endpoint, which is the incidence of all treatment-emergent adverse events. The serious-event terms are reported as percentages, but their denominators and group context are not stated. These limits prevent a full reconstruction of the safety profile from the registry entry.

The counts do not establish a causal relationship between SL-172154 and any event. Nor do they establish that a dose is safer or less safe than another. The design is sequential and open-label, without a randomized control group; the groups are small and may not be comparable. No inferential analyses or uncertainty estimates are listed. The numerical differences across groups should therefore remain descriptive.

The study summary states that antitumor activity and pharmacodynamic effects were among its evaluation aims, and objective response rate is listed as a secondary outcome. Results for those measures are not reported in the registry record. The safety information alone cannot establish antitumor activity, comparative benefit, or a clinical effect.

The study's terminated status is recorded, but the reason is not reported. It should not be treated as evidence about safety, efficacy, feasibility, or a decision to stop for any particular reason. Overall, the record offers limited descriptive safety information from an early-phase dose-escalation study; it does not support a definitive comparative or causal conclusion.

14. Why This Trial Matters Statistically

This study illustrates a central statistical distinction: a registry can define an endpoint without reporting its result. Here, the primary endpoint is the number of participants with treatment-emergent adverse events, but that overall endpoint result is not reported in the registry record. Serious and other adverse-event counts add useful descriptive context, yet they do not fill that reporting gap or establish the complete primary endpoint.

The study also illustrates why design matters when interpreting group differences. Sequential dose escalation is intended to study dose levels in sequence; it is not equivalent to random assignment between concurrent treatment groups. In general, the observed groups can differ in ways that affect event counts, so an unadjusted contrast does not isolate the effect of dose. The registry reports no inferential analyses that would address uncertainty, and statistical adjustment cannot recreate a randomized control group.

Small groups make precision a key issue. Counts can be stated exactly for the participants represented, but they may not estimate event frequency precisely beyond those participants. Percentages for serious-event terms are difficult to interpret without a reported denominator and cohort context. This is a practical reminder that a percentage is meaningful only alongside its underlying population and definition.

Finally, the study has multiple registered outcome measures, while the registry lists no analyses. This makes it important to distinguish stated objectives from reported evidence and to avoid treating unreported outcomes as either positive or negative. The record is statistically informative about the limits of what can be concluded, as well as about the safety counts it records.

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 safety groups are small, and the study has no randomized control group. The sequential dose-escalation design and open-label status limit direct comparisons between dose groups. The registry does not report enough detail about enrollment flow, cohort characteristics, exposure duration by participant, or dose-escalation decisions to assess whether the groups were comparable.

The primary endpoint is defined, but its numerical result and analysis population are not reported. Serious and other adverse-event counts are available, but the full set of treatment-emergent events, event relatedness, and participant-level overlap are not reported. The serious-event term percentages lack a stated denominator and dose-group context. The death count is listed without cause or attribution.

The record lists the study as terminated, but does not report why. It also does not report missing-data methods, a statistical analysis plan, confidence intervals, hypothesis tests, or multiplicity handling. Results for objective response rate, immunogenicity, and pharmacokinetic outcomes are not reported in the registry record. These gaps limit interpretation of both safety and the other stated study aims.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ph1 Study of SL-172154 Administered Intratumorally in Subjects With Squamous Cell Carcinoma of the Head and Neck or Skin — NCT04502888.
• Registry record last updated 2025-02-24; status last verified 2025-01.
• Results first posted 2025-02-24.
• 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

NCT04502888 is a Phase 1, open-label, multicenter, sequential dose-escalation study of intratumoral SL-172154 in cutaneous squamous cell carcinoma or squamous cell carcinoma of the head and neck. The registry lists Shattuck Labs, Inc. as sponsor, enrollment of 5, a start date of 2020-09-17, a primary completion date of 2022-04-08, and status as terminated.

The primary endpoint is incidence of all treatment-emergent adverse events. Safety summaries list groups receiving SL-172154 (0.003 mg) and SL-172154 (0.01 mg), with counts for serious and other adverse events and deaths. The registry lists 15 outcome measures and 0 analyses. A complete result for the primary endpoint, results for the listed secondary outcomes, the reason for termination, and the statistical analysis plan are not reported in the registry record.