BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors (NCT04455620), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs) During the DLT Evaluation Period in Part 1.

2. Clinical Question

3. Trial Design

This was an open-label, multicenter Phase I/IIa study of BNT151 in participants with solid tumors. Its stated aims included evaluating safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy. The record lists BioNTech SE as the sponsor, 49 participants enrolled, and study status as terminated. The listed study start was 2021-01-26, and the listed primary completion was 2024-05-28.

The study plan included Part 1 monotherapy dose escalation, Part 2A combination dose escalation, and Part 2B. Part 1 enrolled participants with various advanced or metastatic solid tumors under the eligibility circumstances described in the registry record. Dose escalation was planned with an accelerated titration approach: beginning with single-participant cohorts and proceeding to larger cohorts informed by a 3+3 design. The monotherapy arm description states that dose escalation was intended to continue until the maximum tolerated dose and/or recommended Phase II dose.

Part 2 was not conducted because the study was terminated early. A dedicated monotherapy biomarker cohort was planned but was not opened, so no data were generated for it. The record describes adaptive design elements as planned, but the details of their implementation are not reported in the registry record. The reasons for early termination beyond the statement that the study was terminated early are not reported in the registry record.

The registry lists no masking and no randomized allocation. Consequently, the dose groups are descriptive groups within a sequential dose-escalation study, not randomized treatment arms suitable for an unadjusted causal comparison. Safety listings are available for the dose groups, but the primary endpoint count and analysis results 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.

Before assignment: A total of 49 participants were enrolled in this study and all participants received at least one dose of the IMP.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT evaluable set, including all participants from the safety set who were enrolled in dose-escalation cohorts and either experienced a DLT during the DLT evaluation period (Cycle 1) or completed the DLT evaluation period. Participants who did not experience any DLT during the DLT observation period were considered to be evaluable if they have been observed for minimum 21 days following the first dose and were considered to have sufficient safety data to conclude that a DLT did not occur.

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: Treated set, i.e., defined as all participants who received IMP (i.e., at least one dose of BNT151).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs) During the DLT Evaluation Period in Part 1, measured over From first dose of IMP up to 21 days (Cycle 1)..

The primary endpoint was the number of participants with dose-limiting toxicities during the DLT evaluation period in Part 1. The stated period ran from the first dose of investigational medicinal product through 21 days, identified as Cycle 1. The endpoint population was the DLT-evaluable set: participants in the safety set who entered dose-escalation cohorts and either experienced a DLT during the observation period or completed that period. Further details of the population definition are not reported in the registry record.

In general, an early dose-escalation study uses a defined short-term toxicity endpoint to identify whether a dose has unacceptable toxicity under the protocol’s criteria. Such information can contribute to dose selection for later study. The registry describes Part 1 as dose escalation toward the maximum tolerated dose and/or recommended Phase II dose, but does not report the specific toxicity criteria used to classify a DLT or a result for this endpoint.

The endpoint is a participant count, not a measure of tumor response or duration of disease control. Objective response rate, disease control rate, and duration of response are listed as secondary outcomes. Their results are not reported in the registry record. The primary endpoint result is also not reported in the registry record, so the number of participants meeting the DLT definition cannot be interpreted from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It identifies the primary endpoint, its time window, and a DLT-evaluable population, but does not report the endpoint count, an effect estimate, a confidence interval, or analysis results. It also does not report a statistical analysis plan. The study’s early-phase and sequential dose-escalation structure is important when considering what types of comparisons are meaningful.

What does a participant count represent?

The primary endpoint is a count of participants with at least one qualifying DLT during the specified evaluation period. In general, a count answers how many participants met the endpoint definition in the relevant analysis population. It is not the same as the number of distinct toxicity events: one participant could potentially experience more than one event, while the endpoint described is the number of participants. The registry record does not report the count or the detailed criteria defining a DLT.

The denominator also matters. The endpoint population is described as the DLT-evaluable set, drawn from the safety set and restricted to participants enrolled in dose-escalation cohorts who experienced a DLT during the evaluation period or completed that period. This is not necessarily identical to total enrollment. The record lists 49 enrolled participants overall, but does not report the number in the endpoint analysis population.

Why does the dose-escalation structure matter?

In general, sequential dose escalation assigns participants to dose cohorts over time, with later cohorts informed by earlier experience. The record says the study began with single-participant cohorts and then used larger cohorts informed by a 3+3 design. This approach is designed for early dose evaluation, rather than for estimating a randomized treatment effect against a concurrent control group. The registry describes adaptive design elements as planned, but specific decision rules and their implementation are not reported in the registry record.

The study’s allocation is listed as not applicable and masking as none. These features, together with sequential enrollment, mean that observed differences between dose groups should be treated descriptively. In general, differences can reflect the dose, but can also reflect differences in participants or the time at which cohorts enrolled. The record cautions that the groups are not a like-for-like control comparison.

How should uncertainty be understood?

In general, a point estimate gives a single summary of an observed effect or event frequency, while a confidence interval expresses uncertainty around that estimate under the chosen statistical model. A wide interval indicates less precision than a narrow interval. No primary endpoint estimate or confidence interval is reported in the registry record, so neither the observed DLT frequency nor its statistical uncertainty can be evaluated from the posted results.

In general, small groups can yield imprecise estimates, especially when the outcome is uncommon. A zero count in a group would not by itself prove that the underlying risk is zero. Here, the primary endpoint group counts are not reported, so even a descriptive assessment of DLT frequency by dose cannot be made from the registry record.

What do the planning assumptions mean?

The sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect to detect is expressed as a fraction of an observed effect. For time-to-event settings, the planning convention is a total number of events; for other settings, it is participants per arm. These are planning calculations, not observed power and not evidence that an effect was demonstrated.

In general, a planning calculation depends on the assumed effect, outcome variability, allocation, significance level, and analysis method. The record does not report the trial’s own sample-size justification. The study also has no randomized comparator, so a hypothetical two-arm planning illustration should not be confused with the actual sequential dose-escalation design. No planning figure can replace the missing endpoint result.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume that variability follows a particular relationship to the mean. Over-dispersion means the observed variability is greater than that assumed by a simpler model; ignoring it can make uncertainty appear smaller than it is. This is a general consideration for count-data analyses. The primary endpoint is specified as a participant count, but the registry record does not report a count model or any analysis method, so it is not possible to say whether over-dispersion was assessed or relevant to a reported estimate.

The registry lists six outcome measures and no analysis results. It does not report the statistical methods used for the primary or secondary outcomes, any confidence interval method, adjustment for covariates, interim analyses, or a multiplicity strategy. Those methods should not be inferred from the general study description or from the planning assumptions.

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("BNT151 0.4 ug/kg", "BNT151 2.0 ug/kg", "BNT151 4.0 ug/kg", "BNT151 8.0 ug/kg", "BNT151 2.0 + 4.0 ug/kg")
n      <- c(1, 8, 24, 2, 14)
events <- c(0, 0, 0, 2, 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  BNT151 0.4 ug/kg  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  BNT151 2.0 ug/kg  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  BNT151 4.0 ug/kg  24  0  0.0  0.0  14.2  0.0  13.8  0.1  13.7
ARM  BNT151 8.0 ug/kg  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  BNT151 2.0 + 4.0 ug/kg  14  0  0.0  0.0  23.2  0.0  21.5  0.2  21.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures, including the primary DLT endpoint and secondary outcomes of objective response rate, disease control rate, and duration of response. It does not report results for these outcomes or an analysis strategy explaining how they were evaluated together. A plan for controlling multiplicity, such as a testing hierarchy or adjustment across multiple hypotheses, is not reported in the registry record.

In general, testing several outcomes can increase the chance of at least one apparently unusual result if each is assessed separately. Multiplicity methods can define which findings are confirmatory and how uncertainty is interpreted across outcomes. Without a reported analysis plan or outcome results, it is not possible to determine whether any multiplicity procedure was used or how the secondary outcomes should be interpreted inferentially.

The primary endpoint population is described as a DLT-evaluable set drawn from the safety set and dose-escalation cohorts. The registry states that participants who experienced a DLT during the observation period or completed the period were included. The full handling of participants who did not complete the period, withdrew, or had incomplete assessments is not reported in the registry record. Missing-data methods and sensitivity analyses are also not reported in the registry record.

Total enrollment is not interchangeable with the endpoint analysis population. The registry reports 49 enrolled participants but does not report the number of DLT-evaluable participants or how many contributed to each secondary outcome. Part 2 was not conducted after early termination, and the planned biomarker cohort was not opened. The extent to which these changes affected analysis populations or the handling of missing outcomes 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: influenza like illness (50.0%), hyperbilirubinaemia (50.0%), cytokine release syndrome (50.0%), pyrexia (16.7%), ascites (12.5%).

The safety listings are grouped by recorded BNT151 dose. In the 0.4 ug/kg group, 1 participant was at risk for serious adverse events and 0 were affected; other adverse events were listed for 1 of 1, and 1 death was recorded. In the 2.0 ug/kg group, serious adverse events were listed for 3 of 8 participants, other adverse events for 8 of 8, and 6 deaths. In the 4.0 ug/kg group, the corresponding listings were 9 of 24, 24 of 24, and 20 deaths.

For the 8.0 ug/kg group, serious adverse events were listed for 2 of 2 participants, other adverse events for 2 of 2, and 1 death. For the 2.0 + 4.0 ug/kg group, the listings were 4 of 14 with serious adverse events, 14 of 14 with other adverse events, and 7 deaths. These are descriptive counts within groups of different sizes, not randomized comparisons.

The registry also lists serious-event terms with percentages: Influenza like illness, Hyperbilirubinaemia, and Cytokine release syndrome at 50.0% each; Pyrexia at 16.7%; Ascites and Device related infection at 12.5% each. The denominators and further details for these term percentages are not reported in the registry record. The death listings do not establish cause or treatment relationship; those details are not reported in the registry record.

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

The record establishes that BNT151 was investigated in an open-label, early-phase dose-escalation study enrolling participants with solid tumors, and that the study was terminated before Part 2 was conducted. It also documents safety listings across dose groups. These registry entries describe the study’s conduct and the available registry reporting; they do not by themselves establish the frequency of the primary endpoint or an efficacy effect.

The primary question was the number of DLT-evaluable participants with a DLT during the first 21 days of Part 1. That result is not reported in the registry record. The secondary outcomes include objective response rate, disease control rate, and duration of response, but their results are not reported in the registry record. Without those estimates, there is no basis in the posted results to quantify response or disease-control outcomes or their precision.

The safety counts should be read as descriptive records for the listed dose groups. Because the groups were not randomized and were not a like-for-like control comparison, differences between their counts do not isolate a dose effect. The group counts also do not show whether events were related to study treatment. The registry record does not report that relationship for the listed deaths, and the term-level percentages do not have reported denominators in the information available.

In general, absence of a reported result is not evidence that the event did not occur, nor does it establish a particular treatment effect. It means that the corresponding estimate cannot be assessed from the registry record. Likewise, the total enrollment of 49 does not tell how many participants contributed to a particular endpoint, since the analysis population may differ from the enrollment count.

Accordingly, the posted information supports a description of the design, study status, stated endpoint, and recorded safety listings. It does not support a comparative efficacy conclusion, a precise estimate of DLT frequency, or a conclusion about the causes of deaths. Any interpretation should remain within those limits.

14. Why This Trial Matters Statistically

This study illustrates the distinction between an early dose-escalation question and a confirmatory treatment comparison. Its primary endpoint focused on dose-limiting toxicities during a defined evaluation period, and the monotherapy portion was intended to escalate dose toward the maximum tolerated dose and/or recommended Phase II dose. That is a different aim from estimating whether a treatment improves an outcome relative to a randomized control group.

Sequential cohort designs are informative for describing dose escalation, but their dose groups should not be interpreted as if participants had been randomly assigned among concurrent alternatives. The registry explicitly identifies the absence of randomized allocation and notes that the arms are not a like-for-like comparison. This makes careful separation of descriptive safety information from causal comparisons particularly important.

The record also shows why endpoint definitions and populations matter. The primary endpoint is confined to a DLT-evaluable set and a 21-day period, while enrollment covers the study overall. Those are distinct quantities. Without the endpoint count and the number evaluated, neither the observed frequency nor its precision can be judged. The missing primary and secondary outcome results limit what can be learned about safety and preliminary efficacy from the record.

Finally, the planned study included later portions and a biomarker cohort, but Part 2 was not conducted and the biomarker cohort was not opened. This helps distinguish planned objectives from data actually generated. For statistical interpretation, a protocol plan is not equivalent to an observed analysis; conclusions must reflect which populations and outcomes have reported results.

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 is clearly named and its evaluation period is stated, but the number of participants with DLTs is not reported in the registry record. The number of DLT-evaluable participants is also not reported. As a result, the primary safety endpoint cannot be quantified or assessed for precision from the posted results.

The registry lists 49 participants enrolled overall, but it does not provide the outcome-specific analysis populations or results for the listed secondary outcomes. Objective response rate, disease control rate, and duration of response are named, but their estimates and uncertainty are not reported in the registry record. No analysis results are reported in the registry record.

Early termination meant Part 2 was not conducted, and the planned biomarker cohort was not opened. The reasons for early termination beyond the stated early termination are not reported in the registry record. The record does not report whether early termination affected the planned statistical analyses or the availability of particular outcome data.

The safety counts are descriptive, and the groups are not randomized control arms. The registry does not report the relationship of the listed deaths to treatment, the detailed denominators for serious-event term percentages, or the criteria used to identify DLTs. Missing-data handling, multiplicity procedures, interim analyses, and the statistical analysis plan are not reported in the registry record. These omissions limit assessment of both the completeness and the inferential strength of the posted results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BNT151 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With Solid Tumors — NCT04455620.
• 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

NCT04455620 is an open-label Phase I/IIa study of BNT151 in participants with solid tumors, sponsored by BioNTech SE. The registry lists 49 enrolled participants, no randomized allocation, and terminated status. The listed study start was 2021-01-26, with primary completion on 2024-05-28.

Part 1 was a monotherapy dose-escalation study with a primary endpoint measuring participants with DLTs during the first 21 days. Part 2 was not conducted after early termination, and the planned biomarker cohort was not opened. The registry lists safety counts by dose group but does not report the primary endpoint result, secondary outcome results, or analysis results. The listed dose groups are not randomized comparator arms.