BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment (NCT02326844), a na phase 2 study. The primary outcome is Objective Response (Complete Response (CR) + Partial Response (PR)).

2. Clinical Question

3. Trial Design

This was a phase 2 pilot study of BMN 673 (talazoparib) in ovarian cancer associated with deleterious BRCA1/2 mutations, among people whose disease had progressed after prior PARP inhibitor treatment. The registry lists one group, named Ovarian Cancer Patients, and describes the study model as single group. Allocation is not applicable and masking is none. There is no concurrent control arm, so outcomes are descriptive of the treated group rather than a randomized treatment contrast.

The record lists enrollment of 3 and identifies the National Cancer Institute (NCI) as sponsor. The study started on 2015-03-02, and primary completion is recorded as 2016-04-14. Its status is terminated. The registry record does not report why the study was terminated, so no explanation can be inferred from the status alone.

Participants were to take the study drug orally once daily in 28-day cycles. Response was assessed every 2 cycles, described as an average of 64 days. The brief description also mentions screening and recurring study visits, including blood tests, physical examinations, and imaging; it describes four visits in cycle 1 and one visit each subsequent cycle. The registry lists assessment of adverse events, duration of response, and progression-free survival on talazoparib compared with progression-free survival from first PARP inhibitor exposure as secondary outcomes.

The registry record does not report a statistical analysis plan, a sample-size justification, or details of interim monitoring. The planned design should therefore be distinguished from the available result information: a primary endpoint is defined, but its observed result is 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.

Overall Study

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 Objective Response (Complete Response (CR) + Partial Response (PR)), measured over Every 2 cycles, an average of 64 days.

The primary endpoint is objective response, defined as the number of participants with complete response or partial response. It is assessed using RECIST v1.1. Under the registered description, complete response means disappearance of all target lesions; pathological lymph nodes, whether target or non-target, must have a short axis reduction to <10 mm. Partial response requires at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference.

Objective response is used to describe tumor change during treatment according to prespecified imaging criteria. Combining complete and partial responses gives a count of participants meeting either response definition. It is not, by itself, a measure of how long a response lasts, how long a participant remains progression-free, or how outcomes compare with an untreated or alternative-treatment group. The registry separately lists duration of response and progression-free survival among the secondary outcomes.

The planned assessment interval is every 2 cycles, an average of 64 days. The registry record does not report the number meeting the primary response definition, the number assessed, or an estimated response proportion. Thus, the endpoint definition is available, but the primary outcome result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting a small single-group trial requires separating the outcome definition, the observed data, and the statistical inference. The registry defines the primary outcome as a participant count for objective response. It does not report the response count, an uncertainty interval, or a statistical test for that endpoint. Consequently, the record supports an explanation of what was to be measured, but not an estimate of the study’s response frequency.

What does a response count capture?

A count records how many participants meet the response criteria; it does not account for the magnitude of change beyond the categories in those criteria. The registered endpoint combines complete response and partial response. RECIST v1.1 supplies operational rules so that response is classified using specified lesion changes rather than an informal impression. The record states that assessments were planned every 2 cycles, an average of 64 days, but does not report which assessments were completed or how many participants had evaluable scans.

In general, a response proportion is interpreted in relation to its denominator: the participants eligible for the analysis and the number whose outcome can be classified both matter. The registry record does not report the denominator used for the primary outcome or a missing-assessment rule. No response proportion should therefore be inferred from the enrollment figure alone.

What would uncertainty intervals mean?

In general, a confidence interval describes the range of values compatible with the observed data under a statistical model and its assumptions. It conveys precision, not a guarantee that the true value lies within a particular interval. When data are sparse, intervals for event proportions can be wide, reflecting substantial uncertainty. The registry record does not report a confidence interval for the primary endpoint, and no interval can be interpreted as a registry result.

A p-value, in general, describes how incompatible data are with a specified null model, conditional on the assumptions used. It is not the probability that a treatment works, nor does it by itself express the size or clinical importance of an effect. The registry record does not report a primary-endpoint p-value or a prespecified statistical test. The absence of a reported test should not be filled in by choosing one after the fact.

Why does the design matter?

A single-group study describes outcomes among participants receiving the study intervention. It does not provide a randomized comparator with which to separate treatment-associated changes from changes that might occur under another treatment, over time, or through differences in who enters the study. Randomization and concurrent comparison can support a more direct causal contrast, but neither is part of this registered design. Accordingly, the outcome question is descriptive rather than a direct test of superiority over a control.

The secondary comparison of progression-free survival on talazoparib with progression-free survival from first PARP inhibitor exposure uses periods within the treatment history described by the registry. In general, comparing outcomes from different periods can be affected by differences in timing, eligibility, follow-up, and assessment. The registry record does not provide enough analysis detail to judge how those issues were addressed. That outcome should not be treated as though it came from a randomized comparison.

How should planning calculations be read?

In general, a sample-size calculation asks how much information a future study would need under chosen assumptions about the target effect, variability, significance level, allocation, and statistical method. It is a planning exercise, not an observed trial outcome. The record describes planning illustrations based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It specifies that time-to-event illustrations use total events under the Schoenfeld approach, while other illustrations use participants per arm.

These planning assumptions do not describe the design of this single-group study, which has no two-arm allocation. They also do not establish observed power. Power is a design property under specified assumptions, while a post hoc calculation based on an observed effect can be misleading and does not add evidence to the trial. The registry record does not report the trial’s own sample-size justification or the observed primary response result needed to evaluate such an effect-based illustration.

Over-dispersion is a general issue for count data when variability exceeds what a simple probability model expects. If ignored, standard errors can be too small and intervals too narrow. This trial’s primary endpoint is described as a participant count for a binary response classification, not a repeated count process; the registry record does not report an over-dispersion model or a statistical method for the primary endpoint. No special model should be attributed to the investigators without that information.

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("Ovarian Cancer Patients")
n      <- c(3)
events <- c(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  Ovarian Cancer Patients  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists objective response as the primary outcome and identifies several secondary outcomes, including serious and non-serious adverse events, duration of response, and progression-free survival on talazoparib compared with progression-free survival from first PARP inhibitor exposure. Considering multiple outcomes can raise multiplicity concerns: if many hypotheses are tested, the chance of at least one apparently unusual result can increase. In general, a prespecified analysis plan can state which outcomes are confirmatory, whether tests are adjusted, and how secondary findings should be interpreted.

The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a complete statistical analysis plan. It is therefore not possible to determine from the record whether any adjustment was planned or used. The absence of a reported adjustment should not be mistaken for proof that none was conducted.

The record also does not report how missing outcome data were handled, which participants formed each analysis population, or whether participants with no evaluable response assessment were included in the primary analysis. In general, missingness can affect both the denominator and interpretation of an outcome. Excluding participants without an assessment, classifying them as nonresponders, or using another method can yield different summaries; the registry does not specify which approach applies.

Enrollment is reported as 3, but the registry does not state the analysis denominator for objective response or the populations used for the secondary outcomes. No assumptions about intention-to-treat, per-protocol, safety, or evaluable populations can be made from the record. These details matter especially in a small pilot study because each participant’s classification can have a substantial influence on a group summary.

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: platelet count decreased (33.3%).

The registry reports safety figures for the Ovarian Cancer Patients group, with 3 at risk for serious adverse events and 1 affected. For non-serious adverse events, it reports 3 at risk and 2 affected. Deaths are reported as 0. The most frequently listed serious adverse-event term is platelet count decreased, reported as 33.3%.

These figures are counts from the registered group, not precise estimates of how often an event would occur in a broader population. With a small number of participants, each recorded event has a marked influence on the summary, and the figures provide limited information about the range of possible event rates. The registry record does not provide event-level timing, duration, severity grading details, or a comparison with another treatment group in the information.

The serious and non-serious categories are reported separately. A participant may experience more than one event, so event terms and participant counts should not be treated as interchangeable. The record’s count of participants affected does not describe the total number of events. The listed platelet term is a safety finding, not a measure of efficacy. These data describe what the registry reports and do not support a comparative safety conclusion.

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

The record establishes that a phase 2 pilot study evaluated oral talazoparib in a group selected for ovarian cancer associated with germline BRCA mutation and progression after prior PARP inhibitor treatment. It specifies objective response by RECIST v1.1 as the primary endpoint and gives an assessment schedule. These details clarify the study’s question and how response was intended to be classified.

The record does not report the observed primary response result. It therefore does not establish how many participants had a complete or partial response, what the response proportion was, or how precise any response estimate might be. A defined outcome is not the same as a reported outcome, and the registered enrollment figure does not fill that gap.

Even if outcomes are described for the treated group, the single-group design does not provide a randomized comparison. It cannot by itself show whether outcomes differ from those under another treatment or what would have happened to comparable participants without talazoparib. The secondary comparison involving progression-free survival from earlier PARP inhibitor exposure does not create a concurrent control group.

The safety record lists serious and non-serious adverse-event participant counts and reports no deaths in the group. These observations are descriptive and based on a small registered enrollment; they do not provide a precise estimate of safety in a wider population. The record’s terminated status is a study status, not an explanation of why the study ended. A reason for termination is not reported in the registry record.

Overall, the registry supports a description of the population, intervention, endpoint definition, and limited safety counts. It does not support a conclusion about response frequency or comparative efficacy, and it does not report enough statistical detail to assess the planned or conducted analyses fully.

14. Why This Trial Matters Statistically

This study addresses a defined treatment-history question: talazoparib was studied in people with ovarian cancer associated with germline BRCA mutations whose disease had progressed after prior PARP inhibitor treatment. That setting is statistically distinct from studying a treatment in participants without prior exposure to a related drug. The result of interest is not merely whether tumor measurements changed, but whether participants met an explicitly defined response category after earlier PARP inhibitor therapy.

The registry’s use of RECIST v1.1 makes the primary outcome operational: complete and partial response have specified criteria, and assessments are scheduled over treatment cycles. Clear definitions are valuable because they make outcome classification more reproducible. At the same time, a definition cannot substitute for reporting the observed classifications, the analysis denominator, and uncertainty around an estimate.

The pilot and single-group design also illustrate why design context matters. A small, selected group can be useful for describing feasibility and observed outcomes, but a single-group result does not offer the same comparative evidence as a randomized trial. The registry does not report a trial-specific sample-size justification or a full statistical plan, so the intended inferential role of the study cannot be reconstructed from the record.

For statistical readers, the central lesson is to distinguish a registered research question from an available result. Here the endpoint and population are described, and limited adverse-event counts are reported, but the primary response result is not. That distinction prevents endpoint definitions, planning illustrations, or safety summaries from being mistaken for evidence about the primary efficacy outcome.

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 has important limitations for interpreting this trial. Most notably, it does not report the observed result for the primary endpoint of objective response. It also does not report an analysis denominator, response classifications, an uncertainty interval, or a statistical test for that endpoint. This prevents estimation of the response frequency from the registry information.

The registered enrollment is 3, and the study is single group with no concurrent control arm. Outcomes in such a design cannot support a randomized comparison with another treatment. The secondary comparison with progression-free survival from first PARP inhibitor exposure refers to a different period in participants’ treatment histories; the registry does not provide enough detail to assess the analysis or its assumptions.

The study status is terminated, but the reason for termination is not reported in the registry record. The record also does not report a trial-specific sample-size justification, statistical analysis plan, interim analyses, handling of missing outcome data, analysis populations, or a multiplicity strategy. These omissions leave uncertainty about how outcomes were intended to be summarized and interpreted.

Safety findings are based on the small registered group and are presented as counts. They should not be generalized as precise rates, and the record does not provide a concurrent safety comparator. The registry also does not report enough event-level detail to characterize timing or duration. These limitations apply to interpretation of the record; they do not imply a reason for the study’s termination or an unreported result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment — NCT02326844.
• Registry record last updated 2020-08-18; status last verified 2020-08.
• Results first posted 2017-05-24.
• 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

The registry describes a phase 2 pilot study of oral BMN 673 (talazoparib) in ovarian cancer associated with deleterious BRCA1/2 mutations after prior PARP inhibitor treatment. It is a terminated, single-group, unmasked study, with enrollment of 3 and no concurrent control group. The listed sponsor is the National Cancer Institute (NCI).

The primary outcome is the number of participants with complete or partial response under RECIST v1.1, assessed every 2 cycles, an average of 64 days. The observed primary response result is not reported in the registry record. Secondary outcomes include adverse events, duration of response, and a progression-free survival comparison with the first PARP inhibitor exposure period. Safety figures report serious and non-serious adverse-event counts and 0 deaths. The record does not report why the study was terminated or provide a full statistical analysis plan.