Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101 (NCT04144140), a non-randomized phase 1 study. The primary outcome is Dose Escalation Part: Number of Participants With Dose-limiting Toxicities (DLTs).

2. Clinical Question

The study was designed to assess safety and tolerability and to examine preliminary clinical activity. The primary endpoint focuses on dose-limiting toxicities, or DLTs, that investigators judged related to E7766 and that met prespecified severity and duration criteria. This kind of endpoint is used in early-phase dose escalation to characterize short-term treatment-limiting toxicity while doses are being explored. It is not itself a measure of tumor response or a comparison of clinical benefit against a control treatment.

The registry also lists secondary outcomes concerning response, duration of response, disease control, and plasma concentration and timing of peak concentration. Those listed outcomes do not establish that results were reported: the registry record contains no analysis results. The study status is terminated, and the reason for termination is not reported in the registry record.

3. Trial Design

INSTAL-101 was an open-label, multicenter phase 1/1b study of intratumorally administered E7766 in participants with advanced solid tumors or lymphomas. The registry classifies the study as phase 1, non-randomized, and sequential. Enrollment is listed as 24. The study started on 2020-02-24, primary completion is listed as 2022-07-26, and its current status is terminated.

The study included dose escalation and dose expansion. The dose-escalation groups listed in the safety record are E7766 75 mcg, 150 mcg, 300 mcg, 600 mcg, 780 mcg, and 1000 mcg. The registry states that the dose identified in dose escalation would be used in dose expansion. It does not report the dose selected for expansion in the registry record for this analysis.

Because allocation was non-randomized and the design was sequential, the dose groups do not form randomized treatment and control arms. Participants were not assigned by random allocation, and the registry does not describe a concurrent control group. Differences in recorded outcomes between dose groups would therefore not, by themselves, isolate a causal dose effect: the groups are not established as comparable, and the study sequence matters to interpretation.

The study was unmasked, meaning it was open-label. The registry record does not report details about the rationale for sample size, an interim-analysis plan, or a formal statistical analysis plan. It also does not give a reason for termination. The posted enrollment and study dates describe the record, but they do not provide those missing design details or explain 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: A total of 31 participants were screened, of which 7 were screen failures and 24 were enrolled to receive study treatment in the Dose Escalation Part of this study. The study was terminated due to sponsor's strategic decision, which is unrelated to safety, therefore no participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The DLT analysis set included all participants in the Dose Escalation part who completed Cycle 1 without incurring certain major protocol deviations (for instance those related to dosing or others identified before database lock) with at least 2 E7766 injections during Cycle 1 and were evaluable for DLT, or participants who experienced DLT during Cycle 1.

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: The full analysis set included all participants who received at least 1 dose of study drug. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Dose Escalation Part: Number of Participants With Dose-limiting Toxicities (DLTs), measured over Cycle 1 (Cycle length= 21 days).

The primary endpoint is the number of participants in the dose-escalation part with dose-limiting toxicities during Cycle 1, a cycle with a length of 21 days. DLTs were assessed by the investigator as related to E7766 and according to NCI CTCAE version 5.0. The endpoint is a participant count, rather than a continuous measurement or a time-to-event outcome.

The registry defines qualifying toxicities by severity, duration, and clinical circumstances. These include nonhematologic toxicity at Grade 3 or higher, with an exception for Grade 3 fatigue lasting less than 5 days; asymptomatic Grade 3 or 4 laboratory abnormalities corrected within 72 hours; and specified severe nausea, vomiting, or diarrhea unless lasting more than 48 hours despite optimal supportive care. Hematologic criteria include Grade 4 neutropenia for at least 5 days or febrile neutropenia, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with hemorrhage.

In general, a DLT endpoint helps characterize short-term tolerability during early dose exploration. A participant count can indicate how many people met the toxicity definition, but interpretation also depends on the number and characteristics of participants eligible for analysis. The primary endpoint result is not reported in the registry record, and the endpoint population description ends before its eligibility criteria are fully specified.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count of participants who meet a predefined binary classification: a participant either meets the DLT criteria during Cycle 1 or does not. General statistical interpretation of such a count depends on both the number meeting the criteria and the number eligible for the analysis. The registry record does not report the primary count, and the analysis-population description is incomplete, so neither the endpoint frequency nor its precision can be evaluated from the primary outcome entry.

What does the DLT definition contribute?

In general, a prespecified endpoint definition makes outcome classification more consistent by setting rules before results are interpreted. Here the rules combine toxicity grade with duration or clinical circumstances. For example, the definition distinguishes Grade 3 fatigue lasting less than 5 days from other qualifying nonhematologic toxicity and allows certain asymptomatic laboratory abnormalities if corrected within 72 hours. It also specifies criteria for nausea, vomiting, diarrhea, neutropenia, and thrombocytopenia. The investigator assessed whether toxicities were related to E7766. These rules define the endpoint; they do not supply the observed number of participants who met it.

How should counts across dose groups be read?

In general, a participant count is an absolute frequency, while a proportion relates that count to a denominator. The safety summaries give numbers at risk and numbers affected for serious and other adverse events. Those paired counts describe the listed dose groups, but they are not a randomized comparison. The dose groups were part of a sequential, non-randomized study, and the record does not establish that their participants were otherwise comparable. A difference in counts or proportions across groups therefore cannot be attributed to dose alone. Group size also affects how much information a count contains: a small group can yield a highly variable estimate of an underlying event frequency.

The registry separately lists deaths in each dose group. A death count is not a cause-of-death analysis. Without reported causes, timing, adjudication, or an assessment of relationship to treatment, the counts cannot establish that E7766 caused or did not cause any death. The same caution applies to adverse-event terms: listing an event in a safety record does not by itself establish causality.

What can be inferred from the response outcomes?

The registry lists objective response rate, duration of response, and disease control outcomes using iRECIST and mRECIST v1.1. In general, response criteria provide rules for classifying tumor findings, while duration outcomes concern the time that a response persists. Different criteria can classify findings differently. However, no results or analyses for these secondary outcomes are reported in the registry record. Their listing alone cannot establish the number of responses, the magnitude of any effect, or the precision of an estimate.

The record also lists maximum observed plasma concentration and time to reach that concentration for E7766. In general, these pharmacokinetic measures describe drug concentration and its timing; they are distinct from the clinical toxicity and response endpoints. The registry does not report their analysis results in the registry record for this analysis.

What do planning calculations mean?

In general, a sample-size planning calculation asks how many participants may be needed to detect a prespecified effect under stated assumptions. The planning assumptions described for the posted illustrations include 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. Such calculations are planning illustrations, not observed power and not evidence that a study had a particular probability of detecting an effect. They do not replace the trial's own design rationale, which is not reported in the registry record. The non-randomized dose-escalation design also differs from an equal-allocation comparison between two arms, so those assumptions should not be mistaken for the actual study allocation.

In general, over-dispersion matters when outcome variability is greater than a statistical model assumes: standard errors can then be too small and uncertainty understated if the extra variability is ignored. The primary endpoint is a participant count, but the registry record does not report a fitted model, dispersion estimate, standard error, or confidence interval. No model-based inference about the DLT outcome can therefore be reconstructed from the registry entry.

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("Dose Escalation Part: E7766 75 mcg", "Dose Escalation Part: E7766 150 mcg", "Dose Escalation Part: E7766 300 mcg", "Dose Escalation Part: E7766 600 mcg", "Dose Escalation Part: E7766 780 mcg")
n      <- c(2, 2, 2, 11, 6)
events <- c(0, 0, 0, 2, 1)
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  Dose Escalation Part: E7766 75 mcg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Dose Escalation Part: E7766 150 mcg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Dose Escalation Part: E7766 300 mcg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Dose Escalation Part: E7766 600 mcg  11  2  18.2  2.3  51.8  5.1  47.7  5.5  48.4
ARM  Dose Escalation Part: E7766 780 mcg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures, including a primary DLT count, response and disease-control measures under two response criteria, duration outcomes, and pharmacokinetic measures. It reports 0 analyses. The presence of multiple planned outcomes raises a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. No multiplicity adjustment or hierarchy among secondary outcomes is reported in the registry record.

The record does not report how missing endpoint data were handled, whether participants who discontinued or lacked an assessment were included in particular analyses, or how missing response assessments were treated. The primary population description says participants completed Cycle 1 without certain major protocol deviations and received at least 2 E7766 injections during Cycle 1, but the text ends before completing the eligibility description. The full analysis-set definition is therefore not reported in the registry record.

In general, analysis-population choices affect which participants contribute to an estimate and can influence its interpretation. Without a complete population definition, primary outcome count, and missing-data method, the endpoint cannot be independently interpreted or reproduced from the record. Details of any interim analyses, statistical plan, and sample-size justification are also not reported in the registry record. No inference about those procedures should be drawn from the absence of posted analyses.

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: vomiting (100.0%), localised oedema (50.0%), injection site pain (16.7%), hypertension (16.7%), hypotension (16.7%).

The registry reports serious and other adverse-event counts separately for each dose-escalation group. For serious adverse events, the listed affected and at-risk counts are 0 and 2 at 75 mcg, 0 and 2 at 150 mcg, 1 and 2 at 300 mcg, 3 and 11 at 600 mcg, 3 and 6 at 780 mcg, and 1 and 1 at 1000 mcg. For other adverse events, the corresponding counts are 2 and 2, 2 and 2, 2 and 2, 11 and 11, 6 and 6, and 1 and 1.

These are descriptive counts, not randomized comparisons. The record does not provide a concurrent control group, and the groups are not established as comparable. The deaths listed by group are 1 at 75 mcg, 1 at 150 mcg, 1 at 300 mcg, 4 at 600 mcg, 5 at 780 mcg, and 1 at 1000 mcg. The registry does not report causes or treatment-relatedness for those deaths in the registry record for this analysis.

The serious-event terms listed include Vomiting at 100.0%, Localised oedema at 50.0%, Injection site pain at 16.7%, Hypertension at 16.7%, Hypotension at 16.7%, and Small intestinal obstruction at 9.1%. The denominator for these percentages is not reported in the registry record. The terms and percentages should therefore be read as registry summaries, not as comparative risks or causal conclusions.

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

The registry record describes an early-phase, open-label, sequential study of intratumoral E7766 and defines a short-term primary safety endpoint for dose escalation. It also records adverse-event counts by dose group and lists secondary clinical and pharmacokinetic outcomes. These features make the design and its intended questions clear, but they do not substitute for reported outcome analyses.

The primary DLT count is not reported in the registry record. The listed response outcomes also have no reported results or analyses. As a result, the posted record cannot establish the frequency of DLTs, quantify preliminary clinical activity, or describe the precision of estimates for these outcomes. The safety counts can be described as recorded group summaries, but they do not show that events were caused by treatment or that one dose had a different causal effect from another.

In general, a non-randomized sequential dose-escalation study is suited to descriptive early-phase assessment, not to a controlled estimate of treatment benefit. Without a randomized control group, an observed change or difference cannot be separated from other explanations using the design alone. Likewise, a count without its complete analysis population and uncertainty estimate gives limited information about how precisely an underlying event frequency is known.

The study status is terminated, but the reason for termination is not reported in the registry record. Termination by itself does not explain the safety, efficacy, or operational circumstances of the study. The record supports conclusions about the registered design, endpoint definitions, and the posted adverse-event summaries; it does not support a conclusion that E7766 does or does not work, or a causal conclusion about safety.

14. Why This Trial Matters Statistically

INSTAL-101 illustrates why early-phase safety questions and efficacy questions should be kept distinct. Its primary endpoint was a count of participants with prespecified dose-limiting toxicities during Cycle 1. That endpoint is intended to characterize qualifying short-term toxicities during dose exploration. The registry separately names response, disease-control, duration, and pharmacokinetic outcomes, which address different questions and require their own reported analyses.

The sequential, non-randomized design also matters statistically. Dose groups are not like-for-like control groups, so their adverse-event counts should not be treated as a randomized dose comparison. This is a useful reminder that descriptive group summaries can inform what was recorded while remaining insufficient to establish a causal difference.

The record further shows the importance of complete reporting. A clear endpoint definition is valuable, but interpretation also requires the observed endpoint result, a complete analysis-population definition, and information about missing data and uncertainty. Those primary analysis details are not reported in the registry record. The distinction between an outcome being listed and an outcome having a reported result is especially important when many outcomes are registered.

Finally, safety counts and death counts need context. Without reported causes, treatment-relatedness, or a suitable control group, counts alone cannot resolve causation. For biostatisticians and clinical researchers, the central lesson is to align each claim with the design and information actually reported: describe counts as counts, keep unreported analyses unfilled by assumption, and avoid treating planning calculations as observed evidence.

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 outcome result is not reported in the registry record, and the record lists 0 analyses. This prevents assessment of the primary endpoint estimate and its precision. The description of the DLT analysis population is incomplete: it refers to Cycle 1 completion, certain protocol deviations, at least 2 E7766 injections, and evaluability, but does not finish the eligibility statement.

The non-randomized, sequential design has no like-for-like control comparison. The registry does not report enough information to attribute differences in safety counts across dose groups to dose. The adverse-event record lists deaths, but causes and relationship to E7766 are not reported in the registry record. The denominator used for the listed percentages of serious adverse-event terms is also not reported.

Although response, disease-control, duration, and pharmacokinetic outcomes are listed, their results are not reported in the registry record. The record does not report a complete statistical analysis plan, multiplicity handling, missing-data methods, interim-analysis details, or the rationale for sample size. It also does not state why the study was terminated. These limitations constrain interpretation of the posted summaries and do not establish what unreported analyses would have shown.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101 — NCT04144140.
• Registry record last updated 2024-03-07; status last verified 2023-03.
• Results first posted 2024-03-07.
• 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

INSTAL-101 (NCT04144140) was an open-label, multicenter phase 1/1b study of intratumoral E7766 in participants with advanced solid tumors or lymphomas. The registry classifies it as non-randomized and sequential, with dose escalation and dose expansion. Enrollment is listed as 24; the study started on 2020-02-24, primary completion is listed as 2022-07-26, and status is terminated.

The primary dose-escalation endpoint was the number of participants with DLTs during Cycle 1, which had a cycle length of 21 days. The registry record does not report the primary endpoint result and lists 0 analyses. Safety summaries provide adverse-event counts by dose group, but they are not randomized comparisons. The reason for termination, full analysis-population definition, and key statistical details are not reported in the registry record.