A Phase 1 Study of HS130 in Combination With Viagenpumatucel-L (HS110) in Patients With Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1 Study of HS130 in Combination With Viagenpumatucel-L (HS110) in Patients With Solid Tumors (NCT04116710), a na phase 1 study. The primary outcome is Dose Limiting Toxicity.

2. Clinical Question

The study was registered as a Phase 1, first-in-human dose-escalation study in patients with solid tumors refractory to standard care. In this type of study, investigators examine safety as doses are escalated; the design is not intended to provide a randomized comparison of treatment effects. The registry describes the combination and the endpoint, but it does not report the primary endpoint count or a dose-limiting toxicity analysis. It also does not report a maximum tolerated dose determination. Thus, the record identifies the question the study set out to address, but the posted information does not show the answer to that question.

3. Trial Design

This was a Phase 1, open-label, single-center, single-group dose-escalation study. The registry lists enrollment of 15 and status as completed. The recorded start date was 2019-10-18, and primary completion was 2021-08-12. Participants had advanced solid tumors refractory to standard care. The official title describes the study as first-in-human; the brief summary says it aimed to determine a safe and effective maximum tolerated dose of HS-130 in combination with HS-110.

The intervention was intradermal HS-130 together with HS-110 (viagenpumatucel-L), administered once every 14 days according to the arm description. The record presents four dose cohorts: HS-130 at 150 ng- 600 ng with HS-110 at 150 ng - 300 ng; HS-130 at 600 ng with HS-110 at 600 ng; HS-130 at 1200 ng with HS-110 at 600 ng; and HS-130 at 1200 ng with HS-110 at 1200 ng. The registry says dose levels were determined by the starting dose and escalation steps outlined in the protocol; further protocol details are not reported in the registry record.

There was no masking, and allocation is listed as not applicable. Since this was not a randomized comparison, differences between dose cohorts should not be read as if they came from a controlled, like-for-like comparison. The registry record does not report the rules used to assign participants to dose cohorts, the escalation decision process, or the numbers enrolled in each cohort as a trial-design summary. The adverse-event entries do give cohort-specific numbers at risk, but those figures do not establish that cohort comparisons were planned or statistically tested.

The primary endpoint was the number of participants with dose-limiting toxicity during 1 month. The stated safety population includes all patients who received at least one dose of study drug. Although enrollment and completion status are recorded, the primary endpoint result and a statistical analysis of that endpoint 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety population includes all patients who received at least one dose of study drug.

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: Safety Population

6. Primary Endpoint

The registry lists the primary outcome as Dose Limiting Toxicity, measured over 1 month.

The primary endpoint is the number of patients with dose-limiting toxicity (DLT) during 1 month. It is a count of participants, rather than a continuous measurement or a time-to-event outcome. The safety population is defined as patients who received at least one dose of study drug. The registry does not provide a DLT count, a proportion, or a cohort-specific DLT result, so the endpoint's observed value is not reported in the registry record.

In general, DLT is used in early dose-escalation research to describe toxicity considered important to decisions about increasing or selecting a dose. A count makes the endpoint directly interpretable as the number of participants who met the protocol's DLT definition during the stated assessment period. That count alone does not convey how severe each event was, whether events were related to treatment, or how investigators made escalation decisions. Those interpretations depend on the protocol's event definition, grading rules, attribution procedures, and decision rules. The registry record does not report these details.

The endpoint is safety-oriented, not a measure of tumor response or comparative effectiveness. It should not be conflated with the broader serious adverse event figures. The record gives separate adverse-event information by cohort, but it does not state that all serious events were DLTs or that all DLTs were serious adverse events. Without the endpoint result and its definition, the posted information cannot establish the frequency of DLT or support a conclusion about which dose level was acceptable.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint determine which statistical interpretations are appropriate. This study is recorded as single-group and open-label, with dose escalation across cohorts and no randomized control group. Its primary endpoint is a participant count for dose-limiting toxicity during 1 month. The registry does not report an analysis of that endpoint, so the methods discussion must distinguish what the design can generally address from what is actually posted.

What does a participant count represent?

For a binary event endpoint, each participant is classified according to whether the event occurred under the endpoint definition during the assessment period. The reported count describes how many participants met that definition. It is not the same as a continuous outcome such as a laboratory value, and it is not automatically a rate over person-time. For this trial, the endpoint is explicitly described as the number of patients with DLT, but neither the count nor the DLT definition is reported in the registry record. No proportion or uncertainty interval can therefore be interpreted from the primary endpoint information.

In general, when event counts are reported, a denominator is needed to understand the observed frequency. A count without the number assessed can be difficult to interpret, particularly when participants have differing follow-up or event ascertainment. The registry defines the safety population as patients who received at least one dose, but does not report the primary endpoint count or an endpoint-specific denominator. The cohort-specific adverse-event entries do include numbers at risk for the serious-event data; these are descriptive safety entries and should not be substituted for a missing primary DLT result.

What does dose escalation imply?

In general, dose escalation studies examine safety across planned dose levels and use prespecified rules to guide decisions about increasing, holding, or selecting a dose. Participants in different dose cohorts may have entered at different stages of the study, and the cohorts need not be comparable in the way randomized groups are intended to be. The record states that dose levels were determined by the starting dose and escalation steps in the protocol, but the protocol rules and decision criteria are not reported in the registry record. It is not possible to reconstruct escalation decisions or infer a maximum tolerated dose from the posted information.

The cohort-specific adverse-event counts are not a randomized contrast. General statistical comparisons between nonrandomized cohorts can be confounded by differences in participant characteristics, treatment exposure, follow-up, or the circumstances under which each cohort was recruited. The registry does not report adjustments for such factors, and there is no posted analysis of cohort differences. Accordingly, descriptive cohort figures should not be treated as estimates of a causal dose effect.

What does an uncertainty interval add?

In general, a confidence interval gives a range of values compatible with the observed data under the method's assumptions. It communicates precision as well as the point estimate; it does not guarantee that the true value lies inside the interval. For event counts, precision depends on the amount of information and the analysis method. This record does not report a confidence interval for the DLT endpoint, a point estimate derived from it, or a model-based safety analysis. No precision claim should be inferred from the cohort counts alone.

Over-dispersion is a general issue when count data vary more than a chosen statistical model expects. If present, it can make standard errors too small and confidence intervals too narrow under a model that assumes less variability. This trial's primary endpoint is a count of participants with a binary event, not a repeated event count, and the registry does not report a model or analysis that would permit assessing over-dispersion. It is therefore a general statistical consideration rather than a reported feature of this study.

What do the planning illustrations mean?

In general, a sample-size calculation asks how many participants a future study might need under stated assumptions about the event effect, allocation, significance level, and power. A planning illustration based on an observed effect is conditional on that effect and the selected assumptions; it is not evidence that the original study had a particular probability of detecting an effect. The record describes planning assumptions involving a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of the observed effect. These are planning assumptions, not the trial's documented analysis plan. The record does not report a sponsor sample-size justification or the observed DLT effect from which a relevant planning illustration could be interpreted. Any such planning result should not be read as observed power or as a result of this dose-escalation study.

More broadly, a protocol analysis plan would clarify endpoint definitions, analysis populations, missing-data handling, escalation decisions, and whether any formal hypothesis tests were planned. These details are not reported in the registry record. The registry contains no posted analysis entries for the primary outcome. Consequently, no particular statistical test, model, multiplicity procedure, or missing-data method can be attributed to the trial from this 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("Cohort 1: HS-130 (150 ng- 600 ng) + HS-110 (150 ng", "Cohort 2: HS-130 (600 ng) + HS-110 (600 ng) (Viage", "Cohort 3: HS-130 (1200 ng) + HS-110 (600 ng) (Viag", "Cohort 4: HS-130 (1200 ng) + HS-110 (1200 ng) (Via")
n      <- c(4, 6, 3, 2)
events <- c(0, 0, 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  Cohort 1: HS-130 (150 ng- 600 ng) + HS-110 (150 ng  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Cohort 2: HS-130 (600 ng) + HS-110 (600 ng) (Viage  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Cohort 3: HS-130 (1200 ng) + HS-110 (600 ng) (Viag  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 4: HS-130 (1200 ng) + HS-110 (1200 ng) (Via  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns the interpretation of several statistical tests or outcomes considered together. In general, the more tests conducted, the greater the chance of at least one apparently notable result arising by chance if each test is judged independently. Approaches to multiplicity can include prespecified hierarchies, adjusted significance thresholds, or clearly labeling analyses as exploratory. The registry lists one primary outcome measure and no posted analysis entries. It does not report a statistical analysis plan, multiple-testing strategy, or whether additional analyses were planned. Multiplicity control therefore cannot be assessed from the registry record.

Missing-data handling is also not reported in the registry record. The safety population is defined as all patients who received at least one dose of study drug, but the record does not say how participants with incomplete follow-up, unevaluable DLT assessments, withdrawal, or missing event information were handled. A population definition alone does not explain how missing endpoint data were treated or whether all participants in that population contributed to the endpoint analysis.

In general, missing outcome data can affect interpretation when the likelihood of missingness is related to participants' health, treatment exposure, or event status. Different assumptions about missing outcomes can lead to different estimates. No imputation method, sensitivity analysis, or missingness summary is reported for the primary endpoint. The registry's adverse-event counts should therefore be interpreted as posted descriptive information, not as a complete account of the approach to missing safety assessments.

The record does not report interim analyses, stopping rules, or a detailed statistical plan. Those omissions prevent assessment of whether analyses were prespecified or how any decisions were linked to accumulating safety information. They should not be filled in by assumption.

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: embolic stroke (50.0%), intestinal ischaemia (33.3%), bacteremia (16.7%).

The serious adverse-event entries are organized by dose cohort. The record gives 4 participants at risk and 0 affected in Cohort 1; 6 at risk and 1 affected in Cohort 2; 3 at risk and 1 affected in Cohort 3; and 2 at risk and 1 affected in Cohort 4. These figures are descriptive counts in the registry. They do not show whether the events were considered related to treatment, how severe they were, when they occurred, or whether any participant had more than one event.

The record also lists deaths by cohort: 4 in Cohort 1, 6 in Cohort 2, 3 in Cohort 3, and 1 in Cohort 4. It does not report causes or timing, and it does not attribute the deaths to study treatment. Death counts cannot be interpreted as treatment-caused deaths without that context. The top serious adverse-event terms are Embolic Stroke at 50.0%, Intestinal Ischaemia at 33.3%, and Bacteremia at 16.7%; the denominator and basis for those percentages are not reported in the registry record.

These entries are not the primary DLT outcome. The DLT count and its definition are not reported, so serious adverse-event counts should not be treated as a substitute for the missing endpoint result.

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

The registry record establishes that the study was designed to examine HS-130 with HS-110 in a Phase 1 dose-escalation setting and that dose-limiting toxicity during 1 month was the primary endpoint. It also provides cohort-level descriptive safety entries. The record does not report the primary DLT result, an analysis of that endpoint, or a maximum tolerated dose determination. It therefore does not answer the central safety question as posted.

The cohort entries can be read as counts of participants recorded with serious adverse events and deaths, alongside the listed at-risk numbers. They cannot, on their own, establish a difference between dose levels. The study had no randomized control group, and the registry does not provide a statistical comparison or information that would support causal interpretation. The listed deaths are not attributed to treatment in the record. The serious adverse-event term percentages also lack a reported denominator and calculation basis.

In general, a safety observation in an early-phase study is not equivalent to proof of benefit or proof of harm. Interpreting whether an event is related to a treatment requires clinical assessment and study-specific definitions; a registry count does not supply those judgments unless they are explicitly reported. Similarly, a completed study does not mean that all planned endpoints or analyses are available in the registry.

The record can support a description of the study's population, intervention, design, endpoint, and posted adverse-event figures. It cannot support a claim that the combination is safe or unsafe, that one dose level is preferable, or that treatment has a clinical effect. Such conclusions would require outcome definitions, endpoint results, and analysis details not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates a distinction between a study question and a result. A Phase 1 dose-escalation design can be used to organize early safety observations across planned dose levels. But a registry entry that names a dose-limiting toxicity endpoint without reporting its value does not provide the central result needed to assess that endpoint. Enrollment and completed status describe the study record; they do not replace an outcome estimate.

It also shows why design matters when reading cohort-level figures. The four dose cohorts are not randomized comparison groups, and there is no separate control arm. Counts across cohorts may be useful descriptively, but they do not establish a dose-related difference or a causal treatment effect. The absence of a posted analysis means there is no reported inferential result to clarify the uncertainty around those descriptions.

Statistically, the record highlights the need for clear endpoint definitions and analysis populations. The primary endpoint is named and its assessment period and safety population are given, but the DLT criteria and observed count are not reported. Without those details, readers cannot judge how the endpoint was applied or how precisely its result was estimated. The serious adverse-event information is distinct and does not fill this gap.

For clinical researchers and biostatisticians, the key lesson is to separate protocol intent, descriptive safety data, and inferential findings. A stated aim to identify a maximum tolerated dose is not itself evidence that one was identified. The posted information permits a bounded description of design and safety counts, while leaving the primary dose-limiting toxicity question 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.

The primary endpoint result is not reported in the registry record. Although the endpoint is defined as the number of patients with dose-limiting toxicity during 1 month, the observed count, endpoint-specific denominator, and uncertainty estimate are absent. The registry also contains no analysis entries. This prevents direct assessment of the primary safety question and makes it impossible to evaluate the precision of an endpoint estimate.

The record does not report the DLT definition, toxicity grading approach, attribution rules, or dose-escalation decision criteria. Without these details, readers cannot determine how events were classified or how the maximum tolerated dose aim was operationalized. A maximum tolerated dose result is not reported.

The study was single-group and not randomized. Dose cohorts should not be considered equivalent to controlled comparison arms, and the registry does not report an adjusted analysis of cohort differences. The cohort-specific serious adverse-event figures and death counts are descriptive; event causality, timing, and the basis for the listed serious-event percentages are not reported.

Other limitations include the absence of a reported statistical analysis plan, missing-data methods, interim-analysis details, and multiplicity procedures. The record does not report participant characteristics or cohort enrollment as a design summary. These gaps restrict assessment of generalizability, outcome ascertainment, and the statistical basis for any dose decision. The posted information supports description of the registered design and safety entries, but not a comprehensive evaluation of the trial's findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 1 Study of HS130 in Combination With Viagenpumatucel-L (HS110) in Patients With Solid Tumors — NCT04116710.
• Registry record last updated 2023-08-23; status last verified 2022-10.
• Results first posted 2023-08-23.
• 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

NCT04116710 is a completed Phase 1, open-label, single-center, single-group dose-escalation study of intradermal HS-130 combined with HS-110 (viagenpumatucel-L) in adults with advanced solid tumors refractory to standard care. The record lists enrollment of 15 and administration once every 14 days. Its primary endpoint was the number of patients with dose-limiting toxicity during 1 month, among patients who received at least one dose of study drug.

The registry record does not report the primary DLT count, a statistical analysis of that endpoint, or a maximum tolerated dose result. It provides descriptive serious adverse-event and death counts by cohort, but does not report event causality or a randomized comparison. The posted information therefore describes the design and selected safety entries, while leaving the primary endpoint question unresolved.