TTX-030 Single Agent and in Combination With Immunotherapy or Chemotherapy for Patients With Advanced Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for TTX-030 Single Agent and in Combination With Immunotherapy or Chemotherapy for Patients With Advanced Cancers (NCT03884556), a randomized phase 1 study. The primary outcome is Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs).

2. Clinical Question

The study asks whether TTX-030 can be administered alone or alongside other cancer treatments while its safety, tolerability, pharmacokinetics, and anti-tumor activity are assessed. The primary endpoint is the number of participants with a dose-limiting toxicity (DLT) during the specified observation period. The registry also describes objective response rate (ORR) and maximum plasma concentration (Cmax) as secondary outcomes, with ORR designated as a primary endpoint in the Arm 1 and Arm 2 expansion cohorts.

This is an early-phase safety question, not a definitive comparison of clinical benefit. The registry record does not report primary DLT counts for the combination arms in the posted outcome results.

3. Trial Design

The registry describes NCT03884556 as a phase 1/1b study of TTX-030 in people with lymphoma or solid tumor malignancies. Its title covers single-agent treatment and combinations with pembrolizumab or chemotherapy. The study status is completed; the recorded start date is 2019-04-10 and the primary completion date is 2022-11-30. Enrollment is listed as 56.

The allocation field is randomized, masking is none, and the model is sequential. These registry descriptors do not by themselves explain how participants were assigned, whether randomization applied to every cohort, or how dose escalation was governed beyond the information in the outcome description. Further allocation and protocol details are not reported in the registry record.

The listed treatment groups include TTX-030 alone, TTX-030 plus pembrolizumab, and TTX-030 plus gemcitabine and nab-paclitaxel. The primary endpoint results, however, list six single-agent dose-escalation cohorts: TTX-030 at 1.5 mg/kg, 3.0 mg/kg, 6.0 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg. Each cohort’s reported DLT count is zero, with cohort sizes shown as 2, 2, 3, 3, 3, and 6 participants, respectively. A separate Arm 1 expansion group and combination cohorts appear in the adverse-event results, but those are not part of the posted primary DLT results.

The registry says that each Dose Escalation cohort completed its DLT observation window before escalation was allowed within its arm. It also says that participants in each Safety Lead-in cohort were closely monitored for DLTs. This sequential structure means the dose groups should not be treated as if they were a single randomized head-to-head comparison. The registry record does not report a sample-size justification, a detailed statistical analysis plan, or the rationale for the number of participants in each cohort.

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.

Only the first 6 of 10 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants in the Dose Escalation cohorts who received 1 infusion during the treatment cycle and completed safety evaluations through the end of the DLT period or experienced a DLT before the end of the DLT period (ie, participants started Cycle 2 or experienced a DLT).

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: Histologically confirmed diagnosis of unresectable or metastatic solid tumor malignancy, or relapsed/refractory lymphoma, for which all standard therapies had been previously given.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs), measured over 1 cycle (each cycle is 21-28 days).

The primary endpoint is the number of participants who experienced DLTs during Treatment Cycle 1. The registry defines a DLT as a clinically significant adverse event that occurred in that cycle, was considered possibly or likely related to TTX-030 or its combination by the Investigator or Sponsor, and met specified severity criteria. These include a Grade 5 event, Grade 4 hematological toxicity, Grade 3 or higher non-hematological toxicity, or Grade 3 or higher immune-related adverse event. Asymptomatic laboratory abnormalities deemed not clinically significant were not counted as DLTs.

In general, early-phase studies use DLTs to characterize tolerability during a defined treatment window and to inform dose-escalation decisions. Counting participants with a DLT is a direct way to report how many met the study’s event definition within that window. It is not a comprehensive summary of every adverse event, nor does a zero count establish that a dose has no safety risks. The outcome also depends on the stated observation period, event criteria, attribution rules, and analysis population.

The registry’s primary-outcome population is restricted to Dose Escalation cohort participants who received an infusion and either completed safety evaluations through the end of the DLT period or experienced a DLT before the period ended. The listed timeframe is one cycle, with each cycle described as 21-28 days. The record does not provide uncertainty intervals or other inferential estimates for these counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants with a qualifying event, not a continuous measurement or a time-to-event endpoint. The posted results give the number of participants with DLTs and the cohort size for each listed dose. In general, binary event outcomes are often expressed as counts and proportions, but the registry’s primary results are counts. No additional proportion or interval estimate is reported for these DLT results.

What does the DLT count represent?

The endpoint is defined by several conditions that must be considered together: the event must occur during Treatment Cycle 1, be clinically significant, be considered possibly or likely related to study treatment, and meet the listed severity criteria. The definition also excludes asymptomatic laboratory abnormalities judged not clinically significant. Thus, the count is not a count of every adverse event, and it is not solely a tally of events by severity. It is a participant-level outcome based on the study’s attribution and classification rules.

The analysis population is also explicitly qualified. Participants in the Dose Escalation cohorts had to receive one infusion and complete safety evaluations through the end of the DLT period or experience a DLT before its end. This definition helps establish who could contribute to the endpoint, but the registry does not report participant-level disposition or explain how any cases outside that definition were handled. Missing-data methods are not reported in the registry record.

Why are dose cohorts described separately?

The registry calls the model sequential and states that Dose Escalation cohorts completed the DLT observation window before escalation was allowed within an arm. In general, sequential dose escalation is organized to evaluate doses in an ordered process, with safety observations informing progression. It is not automatically equivalent to a randomized comparison of every dose. Counts from different dose cohorts should therefore be read descriptively unless a suitable comparative analysis is reported. No such analysis is reported for these primary DLT counts.

The record also describes Safety Lead-in cohorts as closely monitored for DLTs. It does not provide the full decision rules used to move between doses, the planned cohort sizes, stopping boundaries, or any interim-analysis procedures. Those details are not reported in the registry record and should not be inferred from the observed counts.

What can be inferred from zero observed events?

In general, an event count of zero means no participant in the stated analysis group met the endpoint definition during the specified period. It does not mean the event is impossible, and it does not establish that the same result would occur in a larger or different population. Statistical uncertainty is especially important when groups are small. An interval estimate could communicate uncertainty around an event rate, but no such interval is reported for the primary results. No new estimate should be constructed from the posted counts when interpreting the registry’s stated findings.

The primary DLT outcome is confined to Cycle 1. It cannot describe all events over the full treatment course or establish the long-term safety profile. The record lists adverse-event summaries separately, including serious adverse events and other adverse events, but those summaries do not replace the defined primary outcome.

What statistical analysis is reported?

The registry record does not report a statistical analysis plan for the primary endpoint, an inferential comparison among doses, a p-value, or a confidence interval. It does not report a sample-size justification. A record of zero posted analyses means that analysis results are not listed in the available registry information; it does not establish what analyses may have been conducted outside that record.

General statistical practice distinguishes descriptive reporting from hypothesis testing. Descriptive counts state what was observed. Hypothesis tests or model-based analyses require a defined comparison, assumptions, and a specified analysis population. Since no such primary comparison is reported, the dose-specific counts should not be interpreted as a test of differences between doses or regimens.

The registry’s allocation descriptor is randomized, while the primary results list sequential single-agent dose cohorts. Without further details, the relationship between randomization and these cohorts is unclear. The record does not specify whether randomization applied across all study groups or how randomization was implemented. No statistical adjustment for baseline characteristics or other factors is reported.

The study lists ORR and Cmax as secondary outcomes, with ORR also designated as a primary endpoint for the Arm 1 and Arm 2 expansion cohorts. Their numerical findings are not reported in the registry record in the information available for this analysis. Accordingly, those outcomes cannot be used to supplement or qualify the DLT counts.

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("Arm 1: TTX-030 1.5 mg/kg", "Arm 1: TTX-030 3.0 mg/kg", "Arm 1: TTX-030 6.0 mg/kg", "Arm 1: TTX-030 10 mg/kg", "Arm 1: TTX-030 20 mg/kg", "Arm 1: TTX-030 40 mg/kg")
n      <- c(2, 2, 3, 3, 3, 6)
events <- c(0, 0, 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  Arm 1: TTX-030 1.5 mg/kg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Arm 1: TTX-030 3.0 mg/kg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Arm 1: TTX-030 6.0 mg/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Arm 1: TTX-030 10 mg/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Arm 1: TTX-030 20 mg/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Arm 1: TTX-030 40 mg/kg  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes: DLTs as the primary endpoint, and ORR and Cmax among the secondary outcomes. It also states that ORR was a primary endpoint for the Arm 1 and Arm 2 expansion cohorts. This means endpoint roles vary by cohort, but the registry record does not report how multiple outcomes or cohort-specific questions were handled statistically. Any multiplicity procedure, such as adjustment of significance thresholds or a hierarchy for testing, is not reported in the registry record.

No p-values or inferential tests are reported for the primary DLT counts, so there is no posted hypothesis-testing result to interpret as adjusted or unadjusted. The absence of a reported adjustment should not be taken to mean that multiplicity was formally addressed or ignored in the study’s full analysis; the registry does not provide that detail.

The endpoint population is defined as Dose Escalation participants who received one infusion and completed the safety evaluations through the DLT period or experienced a DLT before its end. The record does not give a participant flow account showing how many were screened, treated, excluded from this endpoint population, or missing required assessments. It does not explain imputation, censoring, or other missing-data handling. Those methods are not reported in the registry record.

Enrollment is listed as 56, but the posted primary results cover only the six dose-escalation groups with reported DLT counts. Enrollment should not be assumed to equal the endpoint analysis population for any particular outcome. The record does not provide enough information to reconcile overall enrollment with the outcome-specific cohorts or to determine the contribution of all enrolled participants to each analysis.

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: anemia (50.0%), hyperbilirubinemia (50.0%), allergy to arthropod sting (50.0%), muscular weakness (33.3%), sepsis (25.0%).

The registry’s adverse-event results distinguish serious adverse events, other adverse events, and deaths. These are separate categories and should not be treated as interchangeable. For example, the results list serious adverse events affecting participants in several groups, while the other-adverse-event counts are also presented by group. The counts describe participants, not necessarily the total number of individual events.

Group sizes differ across the listed cohorts. The serious-event figures include 1 of 1 in the Arm 1 0.5 mg/kg group, 1 of 2 at 1.5 mg/kg, 1 of 2 at 3.0 mg/kg, 1 of 4 at 6.0 mg/kg, 1 of 3 at 10 mg/kg, 0 of 3 at 20 mg/kg, 4 of 6 at 40 mg/kg, 2 of 8 in the Arm 1 expansion group, 6 of 13 in Arm 2, and 4 of 14 in Arm 4. These adverse-event figures do not answer the primary DLT question, because they use a broader safety category and do not necessarily share the primary endpoint’s timeframe or attribution criteria.

The registry lists deaths by group but does not establish in these figures that deaths were caused by study treatment. Causality should not be inferred from their presence. It also lists selected serious-event terms with percentages, including Anemia and Hyperbilirubinemia at 50.0%, Allergy to arthropod sting at 50.0%, Muscular weakness at 33.3%, Sepsis at 25.0%, and Ascites at 16.7%. The denominator context for those term percentages is not fully explained in the registry record. They should not be interpreted as rates across all enrolled participants.

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

The primary outcome results show no participants recorded with a DLT in each of the six listed single-agent Dose Escalation cohorts during the registry-defined DLT period. This is a descriptive observation for the stated endpoint and analysis population. It is not evidence that no clinically important adverse events occurred: the separate adverse-event summaries report serious and other events in multiple groups.

Nor does a zero DLT count mean that a dose has no risk, that all participants tolerated treatment in the same way, or that safety is established beyond the observation window. DLT criteria are specific, and events outside those criteria may still be clinically relevant. The endpoint covers Treatment Cycle 1, while the registry does not report a complete long-term safety analysis in the results.

The findings do not establish anti-tumor benefit. Although the registry includes ORR and Cmax among its outcomes and describes the study as evaluating anti-tumor activity and pharmacokinetics, numerical results for those outcomes are not reported in the registry record in the information. The primary DLT counts also do not compare the treatment with an untreated group or establish that TTX-030 is better than another treatment.

The study includes combination regimens, but the posted primary DLT counts are for single-agent dose-escalation cohorts. Adverse-event summaries for combination groups cannot be substituted for missing combination DLT results. The randomized allocation descriptor does not supply a reported comparative estimate for the primary endpoint. The registry record also does not report confidence intervals, p-values, or a statistical analysis plan for these results.

In general, early-phase safety findings help characterize what was observed under a defined regimen and monitoring scheme. They are not a guarantee about outcomes in other populations, doses, or treatment settings. The appropriate conclusion is limited to the reported endpoint counts and the specific cohorts and timeframe described by the registry.

14. Why This Trial Matters Statistically

This trial illustrates why the definition and observation window of an endpoint matter. A DLT is not simply any adverse event: the registry applies timing, clinical significance, treatment-relatedness, and severity criteria. Reading the count without those details could lead to an overly broad interpretation of what was measured.

It also illustrates the distinction between a safety endpoint and a comparative treatment effect. The primary results report counts within dose-escalation cohorts, while the registry describes the study model as sequential. Without a reported controlled contrast or inferential analysis, readers should not treat differences between cohorts as evidence of dose-related change. The posted results are descriptive.

The group sizes are small and vary by dose. In general, limited group sizes make estimates imprecise, and a zero event count does not eliminate uncertainty about possible event frequency. The record does not report confidence intervals for the DLT counts, so the precision of an underlying event-rate estimate is not quantified.

Another statistical lesson is that the trial’s overall enrollment is not the same as the analysis population for every outcome. The registry lists enrollment of 56, while the primary endpoint applies to a defined subset and its posted dose-specific results cover selected cohorts. Without detailed participant flow, readers should not assume that every enrolled participant contributed to every endpoint.

Finally, the record distinguishes primary DLT results from other safety summaries and lists efficacy and pharmacokinetic outcomes separately. Keeping these outcome types distinct helps prevent a safety count from being mistaken for evidence of efficacy, or a broader adverse-event summary from being treated as the specifically defined primary endpoint.

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 are limited to six listed single-agent dose-escalation cohorts. The registry does not provide primary DLT counts for the combination cohorts or the Arm 1 expansion cohort, even though those groups appear elsewhere in the record. The posted counts therefore do not represent a complete primary-endpoint comparison across all listed regimens.

The groups are small and not equal in size, and no confidence intervals or other uncertainty estimates are reported for the endpoint counts. No formal comparison between doses is reported. The registry also does not provide a sample-size justification, a detailed statistical analysis plan, interim-analysis information, or dose-escalation decision boundaries. Those aspects are not reported in the registry record.

The endpoint applies to Treatment Cycle 1 and uses investigator or sponsor attribution alongside specific severity criteria. It may not capture every adverse event or later event. The record does not report a complete account of endpoint-specific missing data, participant disposition, or the handling of participants who did not complete the observation period and did not experience a DLT.

The study is described as randomized, unmasked, and sequential, but the registry does not explain how those features related to each cohort or whether randomization governed the primary dose groups. Since no concurrent-control estimate is reported for the primary endpoint, the results cannot support a comparative claim about dose or treatment regimen.

Finally, numerical findings for ORR and Cmax are not reported in the registry record in the information considered. The adverse-event listings provide additional safety context but do not resolve these limitations, and their percentages have incomplete denominator context for the listed event terms.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: TTX-030 Single Agent and in Combination With Immunotherapy or Chemotherapy for Patients With Advanced Cancers — NCT03884556.
• Registry record last updated 2025-07-02; status last verified 2025-06.
• Results first posted 2025-07-02.
• 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

NCT03884556 is a completed phase 1/1b study of TTX-030 alone and in combinations with pembrolizumab or chemotherapy for people with lymphoma or solid tumor malignancies. The registry lists randomized allocation, no masking, a sequential model, enrollment of 56, a start date of 2019-04-10, and a primary completion date of 2022-11-30.

The primary outcome is the number of participants with DLTs during Treatment Cycle 1. The posted primary results list zero DLTs in each of six single-agent Dose Escalation cohorts, with cohort sizes ranging from 2 to 6. Separate adverse-event results include serious events, other events, and deaths across single-agent and combination groups.

The registry lists ORR and Cmax as secondary outcomes and specifies ORR as primary in certain expansion cohorts, but numerical results for those measures are not reported in the registry record in the information considered. No inferential comparison or uncertainty interval is reported for the posted primary counts. Interpretations should remain specific to the endpoint definition, cohorts, and observation period.