Nivolumab in Combination With Talazoparib in Melanoma and Mutations in BRCA or BRCA-ness Genes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nivolumab in Combination With Talazoparib in Melanoma and Mutations in BRCA or BRCA-ness Genes (NCT04187833), a na phase 2 study. The primary outcome is Best Overall Response as Defined by RECIST 1.1 Criteria.

2. Clinical Question

This clinical question is about observed tumor response during treatment with the combination. It is not a randomized comparison of the combination against nivolumab alone, talazoparib alone, or another treatment. Consequently, even a response count would describe outcomes in the study group rather than isolate the effect of the combination relative to a control.

3. Trial Design

The registry record describes a completed phase II study with a single-group model and no masking. It lists allocation as not applicable, consistent with there being no randomized allocation between trial arms. The study was sponsored by Case Comprehensive Cancer Center. Its stated population was patients with unresectable or metastatic melanoma and mutations in BRCA or BRCA-ness genes.

The intervention was nivolumab plus talazoparib. The arm description specifies nivolumab 480mg intravenously every 4 weeks (28 days) and talazoparib 1mg orally daily. Because the study had one group, these details describe the combination regimen, not a head-to-head comparison. The summary says the study team wanted to assess the combination and consider its effectiveness relative to each drug by itself; the record does not describe single-drug control arms.

The registry lists enrollment of 8. Its primary-outcome population description notes that one enrolled patient experienced a decline in health status before treatment and did not receive study treatment. That distinction matters: enrollment does not necessarily mean that every participant began the intervention or contributed information to every endpoint.

The primary outcome was best overall response by RECIST 1.1, with a timeframe of up to 24 months after treatment through study completion, described as an average of 2 years. Secondary outcomes included progression-free survival, treatment-related adverse events, immune-related response and progression-free survival, and overall survival. The record lists the study as completed, with the start and primary-completion dates recorded as 2020-06-05 and 2023-10-13.

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: One patient out of 8 was enrolled but experienced a decline in health status before starting treatment and therefore did not receive any study treatment.

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 Best Overall Response as Defined by RECIST 1.1 Criteria, measured over up to 24 months after treatment through study completion, an average of 2 years.

The primary endpoint is best overall response, expressed as a count of participants whose best response was complete response or partial response under RECIST 1.1. A complete response is defined in the record as disappearance of all target lesions, with pathological lymph nodes reduced in short axis to <10 mm. A partial response is defined as a ≥30% decrease in the sum of the longest dimensions of target lesions, using the baseline sum as the reference.

Best overall response is used to describe the strongest response category recorded over the specified assessment period, rather than a change in a single lesion or a time-to-event outcome. Combining complete and partial responses gives a clear binary endpoint: a participant either met one of those response definitions or did not. The count can therefore communicate how many participants met the stated threshold in this treatment group.

However, a count alone does not describe the precision of an estimated response rate, and the registry record does not report the primary response count or a response-rate estimate. It also does not report details of the assessment schedule, adjudication, or handling of unevaluable participants. The endpoint definition is available, but the posted registry information is insufficient to determine the observed response result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase II trial and identifies a count of participants meeting a response definition as its primary outcome. The statistical interpretation therefore starts with distinguishing the endpoint's definition from its result: the definition is recorded, but the response count and corresponding analysis are not reported in the registry record.

What does a response count represent?

For a binary endpoint, each participant is classified according to whether the specified event occurred. Here, the event is achieving complete or partial response under RECIST 1.1. A count reports how many participants met that definition. To interpret the count as a rate, readers also need a clearly defined denominator: for example, whether it refers to everyone enrolled, everyone who started treatment, or only participants with an evaluable assessment. The registry's primary-outcome description identifies an enrolled patient who did not receive treatment, but does not state the denominator used for a response analysis.

General statistical explanation: a response proportion is an estimate of the chance of meeting the endpoint in a population like the one studied. A confidence interval describes the uncertainty around such an estimate under the assumptions of the chosen method. With a small study group, uncertainty can be substantial, and the interval may be wide. No response estimate or interval is reported for this trial, so neither the magnitude nor the precision of the primary endpoint can be assessed from the registry record.

Why does the single-group structure matter?

A single-group trial can describe what happened among people receiving the regimen, but it does not supply a concurrent randomized control for estimating a treatment contrast. Without a comparator, differences from an external expectation can reflect factors other than the intervention, including who entered the study, how outcomes were assessed, or the natural course of disease. General statistical explanation: random assignment helps balance measured and unmeasured prognostic factors across groups on average, while an uncontrolled design cannot achieve that protection through randomization.

The study summary expresses interest in the combination relative to each drug alone, but the record lists only the combination group. Thus, that comparative question is not answered by a direct within-trial comparison of treatment arms. The record does not report an adjusted or unadjusted comparative effect estimate.

What can a confidence interval add?

General statistical explanation: a point estimate gives a single summary of an observed effect, while a confidence interval shows a range of values compatible with the data and the statistical procedure. An interval is not a guarantee that the true value lies within its endpoints, nor does it remove limitations of design or measurement. For a binary response endpoint, methods may differ in how they calculate intervals, particularly when participant counts are small. The registry record does not state which interval method, if any, was used for the primary endpoint.

Likewise, a p-value is meaningful only in relation to a specified statistical hypothesis and analysis. The record lists no analyses, p-values, or primary-outcome statistical test. It would be inappropriate to infer statistical significance, a null result, or the trial's statistical plan from the endpoint definition alone.

How should planning calculations be read?

General statistical explanation: sample-size calculations are planning exercises based on assumptions about an effect, variability, allocation, and a chosen error rate. They describe what a future study might require under those assumptions; they do not measure the probability that a completed study found a true effect. A planning illustration based on an observed effect is especially dependent on the stability of that estimate. For a one-group trial, a two-arm planning scenario is not a feature of the observed trial design. Any sample-size illustration should therefore be read as hypothetical planning information, not as observed power or evidence of efficacy.

The record does not report its own sample-size justification or statistical analysis plan. In particular, it does not report how the target enrollment was chosen, whether any interim analyses were planned, which analysis population would govern the primary endpoint, or how missing response assessments would be treated. Those omissions prevent reconstruction of the inferential procedure from the registry entry.

What do the event counts establish?

Adverse-event counts are descriptive unless accompanied by a defined comparison and analysis. The registry reports counts of participants affected and a number at risk for the combination group, but those figures alone do not establish causation. General statistical explanation: event attribution, exposure duration, severity, timing, and rules for counting recurrent events can all affect how safety summaries should be interpreted. The record also lists deaths, but does not give enough information to attribute them to treatment or to characterize their timing.

In short, the statistical record contains a clearly named response endpoint and a single-group design, but no reported primary response estimate or inferential analysis. The essential interpretive limits are the missing result, the absence of a control group, and the lack of details about analysis populations and missing outcome data.

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("Nivolumab + Talazoparib")
n      <- c(7)
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  Nivolumab + Talazoparib  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: best overall response as the primary endpoint, along with progression-free survival, treatment-related adverse events, immune-related response, immune-related progression-free survival, and overall survival. The record states that 10 outcome measures are listed, but does not report how the study handled multiplicity across outcomes or across any analyses within an outcome. A multiplicity plan is not reported in the registry record.

General statistical explanation: when researchers examine multiple outcomes or conduct multiple tests, the chance of at least one apparently unusual result can increase. Prespecified priorities and adjustment methods can help readers distinguish confirmatory analyses from exploratory ones. The registry identifies the primary endpoint, but that alone does not reveal whether or how multiplicity was addressed.

Missing-data rules and analysis populations are also not reported in the registry record. The primary-outcome description says one enrolled patient experienced a decline in health status before treatment and received none. This makes it important to know whether response was assessed in an enrolled, treated, or response-evaluable population. The record does not state which population was used for the primary analysis, whether the untreated participant was included in a denominator, or how missing or unevaluable scans were handled.

General statistical explanation: excluding participants without evaluable outcomes can change the population represented by a result, while counting missing outcomes as nonresponse imposes a different assumption. Neither approach can be attributed to this trial based on the record. It also does not report rules for censoring time-to-event outcomes, or the handling of missing safety information. These gaps limit interpretation of any unreported analysis and should not be filled by assumptions.

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: hepatobiliary disorders (12.5%), blood bilirubin increased (12.5%).

For the nivolumab plus talazoparib group, the registry reports 8 participants at risk for serious adverse events and 1 participant affected. It reports 8 at risk for other adverse events and 8 affected. The record also lists 7 deaths. These are registry counts; they are not, on their own, evidence that the regimen caused the events or deaths.

The leading serious-event terms listed are hepatobiliary disorders and Blood bilirubin Increased, each reported as 12.5%. The registry does not provide further event-level detail here, such as timing, duration, recurrence, or the relationship of each event to treatment. It also does not report the detailed basis for the at-risk counts or explain how overlapping event categories should be interpreted.

A count of participants affected is different from a count of event episodes: one participant could experience more than one event. The registry outcome list includes treatment-related adverse events, but the registry entries do not give a result for that specific outcome. The reported serious and other adverse-event counts should therefore be read as descriptive safety information, not as a complete account of treatment attribution or comparative risk.

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

The registry record establishes that this was a completed phase II, single-group study of nivolumab with talazoparib in unresectable or metastatic melanoma with mutations in BRCA or BRCA-ness genes. It also specifies the combination regimen and defines the primary response endpoint using RECIST 1.1. These features clarify the clinical question the study was designed to address.

The record does not report the primary response count or a response-rate estimate. It therefore does not permit a conclusion about how many participants met the endpoint, the size of any response estimate, or its precision. The absence of a posted response result should not be treated as a zero response or as proof that no result exists outside this registry entry.

Even if the response count were available, the single-group design would describe outcomes under the combination, not establish what the outcomes would have been under nivolumab alone, talazoparib alone, or another comparator. The study summary's interest in comparing the combination with each drug by itself is not matched by separate control groups in the design described by the registry.

The adverse-event information is also descriptive. The record reports serious adverse events affecting 1 participant, other adverse events affecting 8, and 7 deaths, but does not establish that these events were caused by treatment. It does not provide enough detail to determine timing, treatment attribution, or comparative safety.

Accordingly, the posted information is useful for understanding the design, the response criteria, and selected safety counts, but it is not enough to judge efficacy or comparative safety. The unreported primary result, small enrollment, lack of a control group, and unspecified analysis details all constrain what can be inferred. These limits concern the evidence available in the registry record and should not be mistaken for a claim about results that may have been reported elsewhere.

14. Why This Trial Matters Statistically

This trial raises a clinically specific statistical question: whether participants in a defined melanoma population met a prespecified response definition while receiving nivolumab with talazoparib. The registry's RECIST 1.1 definition makes the intended response classification explicit, which is important because a result is interpretable only when the event being counted is clear.

It also illustrates why design and outcome reporting need to be read together. A response count from a single-group study would characterize the group observed, but it could not provide the same treatment contrast as a randomized control. The study summary expresses interest in the combination relative to each drug alone, yet the registry describes only the combination group. That difference between a motivating question and the actual design is central to statistical interpretation.

The registry also makes visible a distinction between enrollment and treatment exposure: its primary-outcome description notes that one enrolled patient did not start treatment. This highlights why the denominator and analysis population matter for response outcomes. Without a reported response count, denominator, or missing-data approach, readers cannot determine the observed endpoint result.

Finally, the record demonstrates that detailed endpoint definitions and some safety counts do not substitute for an efficacy estimate and its uncertainty. The primary response result is not reported in the registry record, and the available adverse-event counts do not establish causation. For researchers, the case underscores the value of complete reporting of results, analysis populations, uncertainty measures, and the relationship between the trial design and the question readers hope to answer.

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 central limitation for interpreting this trial from the registry record is that the primary outcome is named and defined, but its numerical result is not reported. The record does not state how many participants had a complete or partial response, provide an estimate of response frequency, or report uncertainty around an estimate.

The single-group design has no concurrent control arm. As a result, the registry entry cannot support a direct comparison of the combination with either drug alone or another regimen. The intended interest in the combination relative to each drug by itself does not create a comparative analysis when the design contains only the combination group.

Enrollment was 8, and the primary-outcome description says one enrolled patient did not receive treatment after a decline in health status. The registry does not identify the primary analysis population, endpoint denominator, response-evaluable count, or approach to participants without an evaluable response. These omissions make the treatment of the untreated participant and other potentially missing outcomes unclear.

The registry lists secondary outcomes, but does not report their numerical results in the registry record recorded. It does not state a statistical analysis plan, sample-size justification, interim-analysis plan, multiplicity approach, or the methods used for outcome analyses. The timing and assessment procedures for response are also not described beyond the stated timeframe and RECIST 1.1 definition.

Safety interpretation is limited because event timing, treatment attribution, duration, and event-level detail are not reported. The counts of affected participants and deaths cannot establish causality or provide a comparative risk estimate. Together, these limitations mean the record supports description of trial structure and selected event counts, but not an efficacy conclusion or a full assessment of safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nivolumab in Combination With Talazoparib in Melanoma and Mutations in BRCA or BRCA-ness Genes — NCT04187833.
• Registry record last updated 2025-01-14; status last verified 2025-01.
• Results first posted 2025-01-14.
• 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

This completed phase II trial enrolled patients with unresectable or metastatic melanoma and mutations in BRCA or BRCA-ness genes. It used a single-group, unmasked design to study nivolumab with talazoparib. The listed regimen was nivolumab 480mg intravenously every 4 weeks (28 days) plus talazoparib 1mg orally daily.

The primary endpoint was the count of participants with complete or partial response under RECIST 1.1, over a timeframe of up to 24 months after treatment through study completion, described as an average of 2 years. The registry record does not report the primary response count or a statistical analysis of that endpoint. It records enrollment of 8 and notes that one enrolled patient did not receive treatment.

The safety summary reports 1 participant affected by serious adverse events, 8 affected by other adverse events, and 7 deaths. These counts do not establish treatment causation. The record does not include a comparator group, so it cannot provide a direct comparison with either drug alone or another treatment.