A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody) in Patients With Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody) in Patients With Solid Tumors (NCT05159388), a na phase 1, phase 2 study. The primary outcome is Safety Measurements: Number of Participants With at Least One DLT in the First 28-days of Treatment.

2. Clinical Question

The study’s stated purpose was to assess the safety and tolerability of PRS-344/S095012 in patients with advanced and/or metastatic solid tumors. Its phase 1-2, open-label design combined dose escalation with cohort expansion. That structure frames the question as an early-stage safety assessment, rather than a randomized comparison of treatment effects.

The primary endpoint concerns whether a participant experienced at least one DLT during the defined observation period. It does not, by itself, describe the full range, timing, severity, or duration of adverse events. The registry also lists secondary outcomes involving drug concentrations, anti-drug antibodies, objective response rate, best overall response, and best tumor shrinkage from baseline. Results for those outcomes are not reported in the registry record.

3. Trial Design

NCT05159388 is listed as a first-in-human, Phase 1-2, open-label, multicenter study of PRS-344/S095012 in patients with solid tumors. Its stated design includes dose escalation and cohort expansion. The registry describes the study model as single group, allocation as NA, and masking as NONE. Enrollment is listed as 46, and the study status is TERMINATED.

The registry lists a start date of 2021-09-08 and a primary completion date of 2025-04-01. These dates describe the recorded study timeline; the reason for termination is not reported in the registry record. The primary outcome is a safety measurement: the number of participants with at least one DLT in the first 28-days of treatment. Its description specifies Phase 1 and the first 28-days of study treatment.

The registry’s adverse-event record separates safety information into groups labelled PRS-344/S095012 12mg, 36mg, 60mg, and 80mg, and PRS-344/S095012 36mg and Obinutuzumab. These group labels do not change the stated single-group, nonrandomized design. In particular, the registry warns that the arms are not a like-for-like control comparison. Differences among their counts may reflect differences in who entered each group or other factors; the registry record does not establish that those differences are caused by dose or by the addition of Obinutuzumab.

The posted record gives no further details on cohort assignment, the conduct of dose escalation, eligibility criteria, or the operational definition of the expansion cohorts; those details are not reported in the registry record. It also does not report the reason the study was terminated. The design information therefore supports describing the study’s broad structure and its stated safety objective, but not reconstructing its conduct beyond what is recorded.

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: This is based on the DLT Evaluable Set which was defined as all participants who received at least 80% of the required Cycle 1 PRS-344/S095012 dose and completed the DLT observation period or who 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.

6. Primary Endpoint

The registry lists the primary outcome as Safety Measurements: Number of Participants With at Least One DLT in the First 28-days of Treatment, measured over 28 days.

The primary endpoint counts participants with at least one dose-limiting toxicity during the first 28-days of study treatment. A participant is counted for this endpoint if the defined DLT occurred at least once in that observation period; the endpoint is not a count of every separate toxicity episode. The registry describes it as a Phase 1 safety measurement and gives the unit as participants.

The endpoint is intended to characterize early treatment safety in a dose-escalation setting. In general, observing DLTs during a specified early period can help describe whether treatment-related toxicities meet the study’s dose-limiting criteria. The registry record does not report the specific criteria used to classify a toxicity as dose-limiting, so their clinical or operational details cannot be assessed from this record.

The primary endpoint population is the DLT Evaluable Set. It includes participants who received at least 80% of the required Cycle 1 PRS-344/S095012 dose and completed the DLT observation period, or who experienced a DLT. This definition matters because the endpoint does not necessarily use every enrolled participant as its denominator. The number included in the DLT Evaluable Set and the number with at least one DLT are not reported in the registry record. The endpoint result therefore cannot be quantified from the posted record.

This measure is not a complete summary of safety. It does not convey all adverse events, their severity, their relationship to treatment, or their course over time. The registry lists adverse-event information separately, but that information should not be substituted for a numerical result on the primary DLT endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is this?

The primary endpoint is a participant-level binary outcome summarized as a count: whether each member of the DLT Evaluable Set had at least one DLT during the first 28-days of treatment. In general, binary outcomes distinguish whether an event occurred, rather than measuring how many times it occurred or how long it lasted. The registry’s endpoint title uses a count of participants, not a reported rate or a time-to-event measure.

For a count to be interpreted as a frequency, the relevant denominator must also be known. Here, the registry defines the eligible analysis population but does not report its size or the number of participants meeting the endpoint. The count and denominator are therefore both needed to characterize the primary endpoint, and neither numerical result is reported in the registry record.

What does the analysis population definition imply?

The DLT Evaluable Set includes participants who received at least 80% of the required Cycle 1 dose and completed the DLT observation period, or participants who experienced a DLT. In general, an endpoint-specific evaluable population can differ from the overall enrolled population because participants may not meet the endpoint’s exposure or follow-up requirements. The registry’s definition makes those requirements explicit, but does not report how many participants met them.

The inclusion of participants who experienced a DLT is important to the stated definition: experiencing a DLT can qualify someone for this set even if the other listed conditions are not met. The record does not provide participant-level data, so it is not possible to assess how this rule affected membership or to reproduce the endpoint calculation.

How should counts and uncertainty be read?

In general, a count reports the observed number of participants meeting a definition. A proportion or rate additionally places that count in relation to a denominator. A confidence interval describes uncertainty around an estimate under the assumptions of its calculation; it does not guarantee that the true value falls within the interval. The registry record reports no primary endpoint count, denominator, proportion, or confidence interval, so none can be interpreted for this outcome.

Likewise, a p value is tied to a specified statistical comparison or hypothesis test. It does not summarize the size or clinical meaning of an effect by itself. No primary endpoint p value or analysis is reported. Because there is no randomized comparator, a treatment-versus-control test is not established by the design description.

What does the single-group design permit?

In general, a single-group dose-escalation study can describe observations within the study and across the groups recorded, but it does not provide the protection against confounding that random assignment can offer. The registry identifies allocation as NA and cautions that the arms are not a like-for-like control comparison. Group counts should therefore be read as descriptive summaries rather than as evidence that one dose or group caused more or fewer events than another.

The record does not report a model, covariate adjustment, or inferential method for comparisons among groups. Without those details, and without a randomized control group, the posted summaries cannot resolve differences in participant characteristics, follow-up, or other factors that could influence observed counts. The record also does not report whether any formal dose-response analysis was undertaken.

What are the planning calculations?

In general, sample-size calculations use assumptions about the outcome, effect to detect, allocation, significance level, and statistical approximation. The stated planning illustration assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These assumptions describe a planning illustration, not the trial’s own design or an observed analysis.

Such illustrations are not observed power. Observed power is not a substitute for reporting the estimate and its uncertainty, and a planning calculation does not show that the trial had adequate power for its actual design. The registry record does not report the sample-size justification for this study. Because this study is described as single group and the posted record does not give a primary endpoint result, the stated two-arm illustration assumptions should not be mistaken for a randomized comparison or for evidence about this study’s ability to detect an effect.

What analysis details remain unknown?

The registry lists 0 analyses. The statistical analysis plan, handling of missing endpoint data, any interim analyses, multiplicity procedures, and any sensitivity analyses are not reported in the registry record. These details matter because they describe how endpoint definitions, incomplete observations, and multiple outcomes are handled. Without them, the analysis cannot be independently 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("PRS-344/S095012 12mg", "PRS-344/S095012 36mg", "PRS-344/S095012 60mg", "PRS-344/S095012 80mg", "PRS-344/S095012 36mg and Obinutuzumab")
n      <- c(4, 7, 10, 3, 12)
events <- c(0, 1, 3, 1, 3)
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  PRS-344/S095012 12mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PRS-344/S095012 36mg  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7
ARM  PRS-344/S095012 60mg  10  3  30.0  6.7  65.2  10.8  60.3  10.9  61.0
ARM  PRS-344/S095012 80mg  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  PRS-344/S095012 36mg and Obinutuzumab  12  3  25.0  5.5  57.2  8.9  53.2  9.1  53.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary DLT endpoint and secondary measures involving drug concentrations, anti-drug antibodies, objective response rate, best overall response, and best tumor shrinkage from baseline. It lists 0 analyses. The registry record does not report how multiplicity across outcomes was addressed, whether any outcomes were designated for confirmatory testing, or whether a hierarchy or adjustment was planned.

In general, when several outcomes are tested, the chance of at least one apparently notable result can increase if each is assessed independently. A prespecified testing strategy can clarify which conclusions are intended to be confirmatory and how uncertainty is controlled. No such strategy is reported in the registry record. The listed outcome measures alone do not establish that formal hypothesis tests were conducted.

The record defines the DLT Evaluable Set but does not report its size or the number of participants with the primary endpoint. It also does not describe how missing outcome observations, incomplete follow-up, or participants outside the evaluable set were handled for other outcomes. In general, missingness can affect interpretation when the likelihood of an outcome being observed is related to participant status or the outcome itself. The available record does not permit an assessment of whether that concern arose or how it was addressed.

The reason for termination, interim analyses, and any protocol changes are not reported in the registry record. It is therefore not possible to determine whether the listed outcomes and analysis populations remained unchanged during conduct of the study. These omissions limit assessment of analysis choices and selective reporting, without establishing that either occurred.

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: malignant neoplasm progression (35.7%), cytokine release syndrome (28.6%), drug-induced liver injury (25.0%), pleural effusion (25.0%), abdominal compartment syndrome (16.7%).

The registry lists serious adverse-event information by group. For PRS-344/S095012 12mg, 1 participant was affected among 4 at risk; other adverse events affected 4 among 4 at risk, and deaths were 3. For PRS-344/S095012 36mg, serious adverse events affected 8 among 9 at risk; other adverse events affected 9 among 9 at risk, and deaths were 5.

For PRS-344/S095012 60mg, serious adverse events affected 12 among 14 at risk; other adverse events affected 14 among 14 at risk, and deaths were 14. For PRS-344/S095012 80mg, serious adverse events affected 3 among 6 at risk; other adverse events affected 6 among 6 at risk, and deaths were 3. For PRS-344/S095012 36mg and Obinutuzumab, serious adverse events affected 11 among 12 at risk; other adverse events affected 12 among 12 at risk, and deaths were 8.

The registry also lists malignant neoplasm progression at 35.7%, cytokine release syndrome at 28.6%, drug-induced liver injury at 25.0%, pleural effusion at 25.0%, abdominal compartment syndrome at 16.7%, and intestinal obstruction at 16.7% among the top serious-event terms. The denominator and calculation basis for those percentages are not reported in the registry record. These summaries should not be treated as the primary DLT result or as proof that the study drug caused an event. The groups are not randomized, and their counts are not a like-for-like comparison.

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

The registry record establishes that NCT05159388 was designed as a first-in-human Phase 1-2, open-label study of PRS-344/S095012 in patients with solid tumors, with dose escalation and cohort expansion. It identifies an early safety endpoint based on DLTs during the first 28-days of treatment and gives a definition for the DLT Evaluable Set. It also records enrollment of 46 and a status of TERMINATED.

What the record does not establish is the observed result for the primary endpoint. The number of DLT-evaluable participants and the number with at least one DLT are not reported in the registry record. There is also no reported analysis, confidence interval, or p value for that endpoint. As a result, the primary safety outcome cannot be quantified or evaluated for precision from the registry information.

The serious adverse-event summaries and death counts provide additional descriptive safety information for the listed groups, but they do not replace the primary endpoint result. The registry does not report a randomized comparator, and it explicitly cautions against treating the groups as like-for-like controls. Descriptive differences between groups therefore cannot by themselves establish that dose or treatment caused a difference.

The record also does not establish efficacy. Although secondary outcomes include objective response rate, best overall response, and best tumor shrinkage from baseline, their results are not reported in the registry record. The presence of these outcomes in the study record is not evidence of a response or benefit.

Finally, the termination status does not explain why the study ended or indicate what its results were. The reason for termination is not reported in the registry record. The responsible interpretation is limited to the design and the safety summaries recorded, while recognizing that key primary endpoint results and analysis details are absent.

14. Why This Trial Matters Statistically

This study illustrates why the analysis population is central to interpreting a safety endpoint. The primary outcome is a count of participants with at least one DLT, but the endpoint applies to a specifically defined DLT Evaluable Set rather than automatically to everyone enrolled. Without the set’s size and the event count, readers cannot derive even a basic frequency or assess its precision.

It also highlights the distinction between a safety endpoint and broader adverse-event summaries. DLTs during the specified observation period, serious adverse events, other adverse events, deaths, and selected serious-event terms are not interchangeable categories. Each answers a different descriptive question, and the registry record does not provide enough detail to map one category onto another.

The design matters when interpreting group-level counts. A dose-escalation and expansion study can record outcomes across dose-labelled groups, but a nonrandomized single-group design does not make those groups control arms. The registry’s explicit caution against like-for-like comparisons is important: contrasts in counts do not alone identify a causal effect.

Finally, the record makes clear that a study’s stated objectives and listed outcomes are not the same as reported results. The primary safety question and several secondary outcomes are identified, but the registry lists no analyses. This distinction is useful for clinical researchers: a registry can describe what a study set out to assess while leaving readers unable to evaluate the outcome estimates, their uncertainty, or the analysis choices.

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 registry record does not report the numerical primary DLT result or the size of the DLT Evaluable Set. This prevents calculation or assessment of the endpoint frequency and leaves unclear how many enrolled participants contributed to that outcome. The record also does not report the specific DLT classification criteria, so the endpoint definition cannot be assessed beyond its stated observation period and population rules.

The analysis plan is not reported in the registry record. The record does not specify how missing data were handled, whether any interim analyses occurred, how multiplicity across the 9 outcome measures was addressed, or whether analyses were adjusted for participant characteristics. The reason for termination is also not reported.

Safety group summaries are not randomized comparisons. Their group labels include different dose levels and a group labelled with Obinutuzumab, but the record does not provide a basis for causal comparisons among them. The denominator and calculation basis for the percentages attached to selected serious-event terms are not reported in the registry record.

The registry lists secondary outcomes but does not report their results. It therefore does not permit interpretation of drug concentrations, anti-drug antibodies, tumor response, or tumor shrinkage. The record’s broad design and safety summaries are informative about what was planned and recorded, but they do not provide a complete analysis of the study’s safety or efficacy outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody) in Patients With Solid Tumors — NCT05159388.
• Registry record last updated 2026-06-16; status last verified 2026-06.
• Results first posted 2026-06-16.
• 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

NCT05159388 is a first-in-human Phase 1-2, open-label, multicenter study of PRS-344/S095012 in patients with solid tumors. Its stated design included dose escalation and cohort expansion. The registry lists a single-group model, allocation as NA, masking as NONE, enrollment of 46, and status TERMINATED.

The primary endpoint is the number of participants with at least one DLT in the first 28-days of treatment, assessed in the DLT Evaluable Set. The registry lists 9 outcome measures and 0 analyses. The primary endpoint result, its evaluable population size, the statistical analysis plan, and the reason for termination are not reported in the registry record. Adverse-event summaries are listed by group, but the groups are not randomized controls and should be interpreted descriptively.