A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors (NCT03343054), a na phase 1 study. The primary outcome is Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT).

2. Clinical Question

The study also assessed safety, pharmacokinetics, and preliminary anti-tumor activity. The expansion part focused on a defined breast cancer population, while the escalation part included adults with advanced solid tumors. These distinct eligibility groups reflect different study aims, not a direct comparison of treatments or patient groups.

3. Trial Design

This was a completed Phase 1 study of talazoparib in Japanese patients with advanced solid tumors. Its two parts were dose escalation and dose expansion. The dose-escalation part was open-label and used sequential cohorts. It evaluated safety, preliminary efficacy, and pharmacokinetics of single-agent talazoparib in adults whose advanced solid tumors were resistant to standard therapy or for whom no standard therapy was available.

The registry description anticipated enrollment of up to 18 participants in dose escalation, with a minimum of 3, depending on observed dose-limiting toxicities. The expansion part assessed talazoparib at the RP2D determined during dose escalation. Its intended population was adults with locally advanced or metastatic breast cancer and deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations. The description states that a minimum of 17 participants evaluable for the primary endpoint would be enrolled in expansion. Overall enrollment was 28.

The listed dose groups were talazoparib 0.75 mg/day and 1.0 mg/day. The record describes sequential allocation and no masking, with no randomized control arm. Consequently, differences between groups cannot be interpreted as randomized treatment effects: dose, study part, eligibility, and the circumstances of enrollment may differ. The record does not report a control treatment or a comparative efficacy analysis.

The study started on 2017-11-30, reached primary completion on 2021-01-11, and is recorded as completed. The registry lists 37 outcome measures. A sample-size justification, detailed statistical analysis plan, and interim-analysis plan 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: Dose escalation period: total 9 participants were screened, enrolled into the study and assigned to study treatment. Dose expansion period: total 22 participants were screened, out of which 3 participants were screen failure. 19 participants actually enrolled into the study and assigned to study treatment. Data reported based on the primary completion date of 11 January 2021.

Dose Escalation Period (Up to 286 Days)

Reasons for not completing this period:

Dose Expansion Period (Up to 502 Days)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The per-protocol analysis set included all enrolled participants who received at least 1 dose of study treatment and who did not have major treatment deviations during the first cycle. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period.

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: Full analysis set (FAS) included all participants assigned to study treatment and who took at least 1 dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT), measured over Cycle 1 (28 days).

The primary endpoint was the number of participants with dose-limiting toxicities in the dose-escalation part during Cycle 1, defined as 28 days. A dose-limiting toxicity was an adverse event attributable to talazoparib that met specified severity or treatment-interruption criteria. The criteria included selected severe blood-count abnormalities, certain clinically important non-hematologic events, specified liver-test abnormalities, and failure to deliver 75% of doses because of toxicities attributable to talazoparib.

This endpoint is used in early dose-escalation studies to describe acute tolerability at the doses being assessed. A count of participants meeting a prespecified definition can inform how often the defined events occurred in the observed escalation group. It does not, by itself, describe every adverse event, longer-term safety, or anti-tumor activity. The definition also determines what qualifies: events outside its criteria are not dose-limiting toxicities for this endpoint, even if they may be clinically relevant or recorded elsewhere.

The analysis population was described as enrolled participants who received at least 1 dose and had no major treatment deviations during the first cycle. Collection and analysis of this endpoint were not planned for dose expansion. The primary endpoint’s participant count is not reported in the registry record, so its observed frequency cannot be described from the posted results addressed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants meeting a defined event criterion. This is a binary outcome at the participant level: each person either met the dose-limiting-toxicity definition during the specified period or did not. A count is straightforward to interpret as an observed number, but a count alone does not express uncertainty or allow fair comparison across groups of different sizes. The registry record does not report the primary endpoint count, so neither the observed count nor its uncertainty can be described.

The safety summaries also distinguish participants affected from participants at risk in each group. Those denominators matter when reading counts: the groups include 3, 6, and 19 participants, respectively. The displayed counts are descriptive. Converting them into a comparative claim would require attention to the design, the different populations, and uncertainty, not just the raw numbers.

Why does the event definition matter?

A dose-limiting toxicity is not interchangeable with any adverse event. It is defined by the protocol’s specific criteria, applies to the first treatment cycle, and requires attribution to talazoparib. The criteria include selected hematologic and non-hematologic events, liver-test findings, and treatment delivery affected by toxicity. This focused definition makes the endpoint relevant to early dose escalation, but it also means that safety summaries using broader adverse-event definitions answer different questions.

In general, a confidence interval describes the range of values compatible with the observed data under a statistical model and method. With small groups, estimates of event frequency can be imprecise, and uncertainty should be considered alongside the count. No confidence interval for the primary endpoint is reported in the registry record. No inferential analyses are listed in the record details addressed.

How should sequential dose groups be read?

Sequential dose escalation is not random assignment. Cohorts are enrolled over the course of dose evaluation, and the expansion part has a separate eligibility definition and purpose. Therefore, the groups may differ in clinical characteristics and study context. General statistical reasoning cautions against interpreting differences in their observed adverse-event counts as causal dose effects. Randomization is one method for balancing measured and unmeasured characteristics on average; it was not used in this study.

Open-label status means masking was absent. Knowledge of treatment can affect reporting or assessment in some settings, although the registry record does not report whether such effects occurred. This is a design consideration, not evidence that any particular reported event was misclassified.

What do the planning illustrations mean?

The registry record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. For time-to-event outcomes, the illustration uses the total number of events; for other outcomes, it uses participants per arm. These are planning assumptions, not observed trial outcomes, and they are not the trial’s own design justification. They should not be interpreted as observed power or as evidence that the study had a particular ability to detect a real effect. The numerical planning results are not reported in the registry record addressed.

In general, statistical power is a design property tied to assumptions about the effect, variability, outcome definition, and analysis. A planning calculation cannot establish whether the observed result is true, and a small or large observed count does not retrospectively prove that a study was adequately powered. The registry record does not report the original sample-size justification or the assumptions used by the investigators to set enrollment targets.

Why can over-dispersion matter in other outcome types?

General statistical explanation: count outcomes can vary more widely than a simple model assumes. When that happens, a model that underestimates variability may produce intervals that are too narrow or tests that are too optimistic. This issue is relevant when selecting methods for count data, but the primary endpoint in this study is defined as participants with an event, and no such model is reported in the registry record. No claim about over-dispersion in this trial can be made from the listed endpoint definition.

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: Talazoparib 0.75 mg", "Dose Escalation: Talazoparib 1.0 mg")
n      <- c(3, 6)
events <- c(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  Dose Escalation: Talazoparib 0.75 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Dose Escalation: Talazoparib 1.0 mg  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 37 outcome measures, spanning safety, laboratory findings, vital signs, and pharmacokinetic measures, among other outcomes. Considering many outcomes raises a general multiplicity issue: if many statistical tests are conducted, the chance of at least one apparently unusual result can increase. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory outcomes can help readers understand how to interpret multiple analyses. A multiplicity strategy is not reported in the registry record.

The primary outcome is specifically the dose-escalation count of participants with dose-limiting toxicities during Cycle 1. Its result is not reported in the registry record. The outcome description says it was not planned to be collected and analyzed for the dose-expansion period. The registry record also lists 0 analyses, so no inferential analysis results are available in the record details addressed. A missing outcome result should not be treated as a count of zero.

The endpoint population is described as enrolled participants who received at least 1 dose and had no major treatment deviations during the first cycle. This is a per-protocol analysis set, and it differs conceptually from including every enrolled participant. The number of participants excluded for major treatment deviations, and the number with missing endpoint assessments, are not reported in the registry record.

General explanation: missing outcome data can affect interpretation when the likelihood of missingness is related to participant characteristics or outcomes. Complete-case summaries may be misleading if participants with unobserved outcomes differ systematically from those observed. The registry record does not report missing-data handling, imputation, sensitivity analyses, or the reasons for any missing observations. It is therefore not possible to assess whether missingness could have influenced the reported safety or endpoint summaries.

The dose-escalation description anticipated enrollment depending on observed dose-limiting toxicities, while the expansion description specified a minimum evaluable enrollment. Those design statements do not replace a statistical analysis plan. The plan for handling multiple outcomes, deviations, and missing data 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: brain cancer metastatic (33.3%), cholelithiasis (5.3%).

The serious adverse-event counts are 1 of 3 participants in dose escalation at 0.75 mg, 0 of 6 in dose escalation at 1.0 mg, and 1 of 19 in dose expansion at 1.0 mg. The corresponding counts for other adverse events are 3 of 3, 6 of 6, and 19 of 19. Deaths are recorded as 0, 0, and 2 in those groups. These figures describe the reported groups; they are not randomized comparisons, and their different enrollment sizes and eligibility contexts should remain in view.

The serious-event terms listed are Brain cancer metastatic, 33.3%, and Cholelithiasis, 5.3%. These percentages are registry entries and should not be read as proof that talazoparib caused the events. The registry record does not report enough detail to identify event timing, duration, participant overlap across terms, or causal attribution. A serious adverse event is also not automatically a dose-limiting toxicity: the latter must meet the separate endpoint definition and occur during Cycle 1 with attribution to treatment.

In general, adverse-event counts describe observed events under the study’s reporting definitions. They do not alone establish comparative risk, explain why an event occurred, or summarize all aspects of clinical severity. The serious-event figures do not supply the missing primary endpoint result.

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

The registry record establishes that this was a Phase 1, open-label study with sequential dose escalation and a separate expansion part. The primary endpoint was designed to count participants with dose-limiting toxicities during the first 28-day cycle in escalation. The endpoint’s definition and analysis population are described, but its participant count is not reported in the registry record. The primary result therefore cannot be interpreted as an observed frequency from the information available.

The posted safety counts show that serious adverse events were recorded in some participants, while other adverse events were recorded for all participants in each listed group. The record also reports two deaths in the expansion group and none in either escalation group. These summaries do not establish whether treatment caused an event or death. Nor do they provide a valid randomized comparison between doses: the study was sequential, open-label, and had no control arm, and the expansion population differed from the escalation population.

The study sought to assess safety, pharmacokinetics, and preliminary anti-tumor activity. However, the numerical primary endpoint result, pharmacokinetic results, and anti-tumor activity results are not reported in the registry record addressed. The study aims should not be mistaken for findings.

General statistical interpretation requires attention to uncertainty as well as observed counts. Small groups can yield imprecise estimates, and the registry record does not provide a confidence interval or comparative effect estimate for the primary endpoint. A planning illustration is not a substitute for an observed estimate or its uncertainty. It also does not show that a study did or did not detect a clinically meaningful effect.

Accordingly, the posted information supports a description of study structure and selected adverse-event counts, but it does not support a conclusion about the magnitude of anti-tumor activity, the primary dose-limiting-toxicity frequency, comparative safety, or causation. Those questions require results and analyses that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early-phase research: dose escalation and expansion can serve different objectives within a single trial record. The escalation part focused on early safety and pharmacokinetics in adults with advanced solid tumors, while expansion focused on a specified breast cancer population. Recognizing that distinction is essential when interpreting counts across the study groups.

The primary endpoint was narrowly defined around dose-limiting toxicities during the first treatment cycle. Such a definition can make early tolerability measurable and relevant to dose evaluation, but it does not represent all possible adverse events or longer-term outcomes. The endpoint result itself is not reported in the registry record, demonstrating why a detailed outcome definition cannot replace a reported estimate.

The safety summaries also show why denominators and design matter. Counts come from groups of different sizes, and the groups were not randomized controls. A direct numerical contrast can appear simple while carrying substantial interpretive limits. Descriptive counts are useful for conveying what was recorded, but causal and comparative claims need an appropriate design and analysis.

Finally, the record lists many outcomes, while the analysis plan and multiplicity approach are not reported. For biostatisticians and clinical researchers, this underscores the value of prespecified outcome priorities, transparent analysis populations, clear missing-data handling, and uncertainty estimates. Without those details and the primary endpoint result, the statistical account remains incomplete even though the study design and some safety summaries are available.

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 limitation for interpretation is that the participant count for the primary dose-limiting-toxicity endpoint is not reported in the registry record. The endpoint was not planned for collection and analysis during dose expansion, so it cannot describe that part of the study. Numerical pharmacokinetic and anti-tumor activity results are also not reported in the registry record.

The study had no randomized control group and was open-label. Dose groups were sequential rather than randomly assigned, and the expansion eligibility criteria differed from those for escalation. The group counts therefore cannot be treated as a controlled comparison of doses or populations. The overall enrollment of 28 does not by itself indicate how many participants contributed to each endpoint analysis beyond the group counts reported for adverse events.

The serious adverse-event summaries do not provide the detail needed to assess event timing, duration, causality, or overlap among terms. The record’s listed serious-event percentages do not answer whether events were treatment-related. Death counts are reported, but cause and attribution are not reported in the registry record.

The detailed statistical analysis plan, sample-size justification, multiplicity approach, missing-data methods, and reasons for any missing outcomes are not reported in the registry record. The endpoint population excludes participants with major treatment deviations during the first cycle, but the number excluded is not reported. These omissions limit assessment of selection, precision, and robustness. The planning assumptions described for sample-size illustrations do not establish the investigators’ original design rationale or the precision of the observed trial findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors — NCT03343054.
• Registry record last updated 2024-08-22; status last verified 2024-07.
• Results first posted 2022-03-10.
• 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

NCT03343054 is a completed Phase 1 study of single-agent talazoparib in Japanese patients with advanced solid tumors. It included open-label, sequential dose escalation and a dose-expansion part for adults with locally advanced or metastatic breast cancer and deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations. Listed doses were 0.75 mg/day and 1.0 mg/day; overall enrollment was 28.

The primary endpoint counted participants with dose-limiting toxicities during Cycle 1, defined as 28 days, in the escalation part. The endpoint result is not reported in the registry record. Adverse-event summaries list serious events in 1 of 3, 0 of 6, and 1 of 19 participants across the three groups; other adverse events in 3 of 3, 6 of 6, and 19 of 19; and deaths of 0, 0, and 2. These are descriptive figures, not randomized comparisons. Numerical pharmacokinetic and anti-tumor activity findings, along with key statistical analysis details, are not reported in the registry record.