Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial) (NCT04173507), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The clinical rationale described in the registry is that immunotherapy, alone or with chemotherapy, may be less effective in lung cancer cells with STK11 mutations than in cells without that mutation. The study examines the combination of talazoparib, a drug described as blocking enzymes involved in cell growth, with the immunotherapy drug avelumab. The stated question is whether responses are observed with this combination in the specified population.

This is a treatment study, not a randomized test of whether adding talazoparib improves outcomes compared with avelumab alone or another treatment. Without a comparator, response and safety findings cannot isolate the contribution of either drug or establish what would have happened to the same participants under an alternative strategy. The record identifies secondary outcomes including progression-free survival, overall survival, duration of response, and serious adverse events related to study drugs. Numerical results for those outcomes are not reported in the registry record.

3. Trial Design

This completed study is identified as NCT04173507 and is a phase II LUNG-MAP treatment trial sponsored by SWOG Cancer Research Network. The registry lists an enrollment of 47 and a single-group model. Allocation is NA, and masking is none. These design features mean the trial evaluates one treatment group without a randomized control arm or masking.

Participants had stage IV or recurrent non-squamous non-small cell lung cancer with pathogenic STK11 genomic alterations. The treatment group received talazoparib and avelumab. Talazoparib was taken by mouth daily; avelumab was infused intravenously over 60 minutes on days 1 and 15. Treatment cycles repeated every 28 days in the absence of disease progression or unacceptable toxicity. The record does not report further details about dose levels or dose modifications.

The study began on 2020-02-14, reached primary completion on 2021-11-24, and has status completed. Its primary outcome was objective response rate, assessed from registration to progression or treatment discontinuation, up to 1 year and 9 months. Secondary outcomes listed in the record include investigator-assessed progression-free survival, overall survival, duration of response, and participants with grade 3 through 5 adverse events related to study drugs.

A single-group design can describe outcomes among people who received the regimen, but it cannot provide a randomized estimate of comparative benefit or harm. Participant selection, disease course, and other influences can affect observed outcomes. The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or a comparator-based hypothesis. It also does not report the numerical primary-endpoint result. Those omissions limit what can be concluded about the study's planned statistical framework and its observed response rate.

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: 47 participants were initially registered. Five participants were ineligible. In all, 42 participants were eligible and received protocol therapy.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible and evaluable participants

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: Eligible participants

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over From date of registration to progression or treatment discontinuation, up to 1 year and 9 months.

Objective response rate is the percentage of eligible and evaluable participants who have a complete or partial response to treatment. The registry defines response using RECIST 1.1 and includes confirmed or unconfirmed responses. A complete response requires disappearance of target and non-target lesions, no new lesions or disease-related symptoms, and specified reduction in lymph-node short-axis size. A partial response requires at least one measurable lesion and a reduction of at least 30% from baseline in the sum of appropriate target-lesion diameters, without unequivocal progression of non-measurable disease or new lesions.

Response rate is used to describe whether tumors shrink according to prespecified imaging criteria. It is a binary-outcome summary at the participant level: each participant is classified according to whether the response definition is met. Reporting a confidence interval alongside the percentage conveys uncertainty in the estimated response rate, especially when the evaluable group is limited.

The endpoint timeframe runs from registration to progression or treatment discontinuation, up to 1 year and 9 months. The registry record does not report the observed percentage or its 95% confidence interval, so the response rate and its precision cannot be interpreted from the record details. Response rate alone also does not convey how long a response lasts, whether progression is delayed, or overall survival; the registry lists duration of response, progression-free survival, and overall survival as separate secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In a single-group study, outcomes are summarized among participants receiving the study treatment. For a binary endpoint such as objective response, each eligible and evaluable participant is classified as having met or not met the response definition. The response rate is the proportion classified as having a response, expressed in the registry as a percentage of participants. It describes the observed group; without a comparator it does not estimate a randomized treatment contrast.

Randomization is useful because it assigns participants to treatment strategies by chance and can reduce systematic differences between comparison groups. This trial is listed as single-group, with allocation NA and no masking, so such a between-group randomized comparison is not part of the design. The registry record does not report an alternative control group. Results from this design are therefore descriptive with respect to the treated group and cannot isolate the effect of one component of the combination.

What does the confidence interval communicate?

A confidence interval gives a range of values compatible with the data under the statistical method used. For an estimated response percentage, it conveys sampling uncertainty: a wider interval indicates less precision, while a narrower interval indicates more precision. It is not a guarantee that the true value lies within the particular interval, nor does it remove possible bias from participant selection, outcome assessment, or missing data.

The primary endpoint is described with a 95% confidence interval, but the numerical response estimate and interval are not reported in the registry record. Therefore, the precision of the primary result cannot be assessed. The registry lists enrollment of 47, but the endpoint population is eligible and evaluable participants; its size is not reported in the registry record. Precision depends on the analyzed participants and observed responses, not simply on the enrollment figure.

Why do endpoint definitions matter?

RECIST 1.1 supplies operational criteria for classifying tumor response. The registry distinguishes complete response from partial response and specifies the measurements and disease assessments involved. Prespecified criteria make the endpoint more reproducible than an informal judgment of improvement. The record includes confirmed or unconfirmed responses, so its endpoint definition is broader than one limited to confirmed responses alone. The record does not provide the number in each response category or further details about assessment procedures.

The endpoint timeframe also defines the observation window: from registration to progression or treatment discontinuation, up to 1 year and 9 months. A response endpoint observed within a specified period is not interchangeable with time-to-event outcomes such as progression-free survival or overall survival. The registry lists those as separate secondary outcomes, alongside duration of response.

How should planning illustrations be understood?

Sample-size illustrations based on an observed effect are planning exercises, not measurements of trial performance. They use assumptions about the significance level, allocation, approximation, and effect size to illustrate a hypothetical future design. The registry record does not report that these illustrations were the trial's own design calculations or justification. A sample size associated with a target power is not the trial's observed power and does not show the probability that the treatment is effective.

In general, sample-size planning asks how many participants a hypothetical study might require to detect a chosen effect under stated assumptions. The answer depends on the endpoint, target effect, variability or event frequency, significance threshold, allocation, and statistical method. If the assumed effect is smaller, more participants are generally needed to distinguish it from random variation, all else equal. That general relationship does not establish what assumptions governed this trial: its protocol-level sample-size rationale is not reported in the registry record.

Why does over-dispersion matter?

For count outcomes, a model may assume that variation follows a particular distribution. Over-dispersion means the observed variability exceeds that assumption. If it is ignored, standard errors can be too small and confidence intervals or tests can appear more certain than warranted. This is a general statistical issue, not a reported feature of this trial. The primary outcome is a percentage based on a binary response classification, and the record does not describe a count model or report an over-dispersion assessment.

What can be inferred from the reported safety counts?

Safety counts are descriptive summaries of participants affected by events, with denominators indicating the group at risk. They do not by themselves establish causation. Relatedness is specified for one serious-adverse-event count, while the record also lists other adverse events and deaths. These categories should not be collapsed into one outcome: they have distinct descriptions and may use different criteria. The record does not provide event-level timing, recurrent-event counts, exposure-adjusted rates, or a comparator group in the registry record.

The posted serious-event terms are percentages, but a percentage should be interpreted in light of the event definition, denominator, follow-up, and reporting practices. Without a control group, the counts cannot show whether the regimen increased or decreased risk relative to another treatment. The registry record also does not report a statistical analysis plan, interim-analysis procedures, or a protocol-level approach to multiplicity.

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("Talazoparib Plus Avelumab")
n      <- c(42)
events <- c(1)
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  Talazoparib Plus Avelumab  42  1  2.4  0.1  12.6  0.4  12.3  0.6  12.3

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or statistical tests are evaluated. The more opportunities there are to identify a result as statistically notable, the greater the chance of a false-positive finding across the set of tests if no adjustment or prespecified hierarchy is used. This is a general statistical consideration. The registry lists objective response rate as the primary outcome and includes progression-free survival, overall survival, duration of response, and treatment-related grade 3 through 5 adverse events as secondary outcomes. The registry record does not report whether these outcomes were tested under a hierarchy or whether any multiplicity adjustment was planned.

The registry record does not report a statistical analysis plan, interim analyses, or a sample-size justification. It also does not report the numerical primary endpoint result or numerical results for the listed secondary efficacy outcomes. Without those details, the intended inferential framework, any prespecified testing sequence, and the handling of missing outcome assessments cannot be established from the registry record.

Missing data can affect both the numerator and denominator of a response-rate estimate. The endpoint population is described as eligible and evaluable participants, while enrollment is listed as 47. The number eligible and evaluable, the reasons for any exclusions, and the handling of participants without response assessments are not reported in the registry record. A missing response assessment should not automatically be treated as either a response or a non-response without knowing the prespecified analysis rule.

The record also does not report whether the outcome assessors were independent or blinded; the overall masking field is none. That design feature may matter when outcomes depend on assessment, although the registry record does not describe the assessment workflow in detail. These gaps do not prove that procedures were absent from the study protocol; they indicate that those procedures are 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: anemia (19.0%), platelet count decreased (9.5%), disease progression (4.8%), respiratory failure (4.8%), febrile neutropenia (2.4%).

The registry lists 42 participants at risk for serious adverse events and 15 with serious adverse events related to study drugs. It separately lists 42 participants at risk for other adverse events and 41 affected. The record also reports 30 deaths. These figures describe the treatment group; there is no randomized control group for comparison. The record does not state that the deaths were caused by study drugs, and the death count should not be interpreted as a treatment-related death count.

The most frequently listed serious-event terms are anemia at 19.0%, platelet count decreased at 9.5%, disease progression at 4.8%, respiratory failure at 4.8%, febrile neutropenia at 2.4%, and atrial flutter at 2.4%. These are registry-listed percentages for the named serious terms. They are not estimates of comparative risk and should be read in the context of the trial's at-risk group and its event definitions.

Serious adverse events, other adverse events, and deaths are distinct summaries. A participant-level count does not show how many event episodes occurred, when they occurred, how long they lasted, or whether they led to treatment changes. Those details are not reported in the registry record. The counts are useful for describing posted safety experience, but they do not establish causation or quantify excess risk versus another treatment.

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

The record documents a phase II study of talazoparib plus avelumab in a defined population with stage IV or recurrent non-squamous non-small cell lung cancer bearing pathogenic STK11 genomic alterations. It describes the regimen, an objective response endpoint based on RECIST 1.1, and selected safety counts. The study is completed, and its registry status is listed as completed.

The primary endpoint is the percentage of eligible and evaluable participants with a confirmed or unconfirmed complete or partial response. The numerical response rate and 95% confidence interval are not reported in the registry record. Without those values, the magnitude and precision of the response result cannot be evaluated. The record's enrollment figure does not substitute for the number analyzed for the endpoint, which is not reported.

Even if a response percentage were available, a single-group result would describe outcomes observed among people receiving the combination. It would not establish that the combination caused those outcomes or that it performs better than a different treatment. There is no randomized comparator in this design, and the registry record does not report a comparative estimate. The results cannot isolate the contribution of talazoparib from that of avelumab.

The listed secondary outcomes could address different questions: progression-free survival concerns time to progression or death under its definition; overall survival concerns time to death; duration of response concerns how long response persists; and adverse-event outcomes describe harms. However, numerical findings for these outcomes are not reported in the registry record. Their presence in the outcome list is not evidence of a particular result.

The safety figures describe participants affected in the treatment group, including serious adverse events related to study drugs, other adverse events, and deaths. They are not a controlled estimate of treatment-attributable risk. As a result, the record supports a clear description of the intended question, design, and posted safety experience, but does not support a numerical conclusion about primary efficacy, comparative effectiveness, or comparative safety.

14. Why This Trial Matters Statistically

This trial raises a statistical question that is important in interpreting early-phase treatment studies: what can a response endpoint tell readers when the study has one treatment group? Objective response rate provides a structured summary of tumor shrinkage under RECIST 1.1. Its usefulness depends on a clearly defined population, consistent assessment, and a reported estimate with uncertainty. In this record, the endpoint definition is described, but the numerical response result and confidence interval are not reported.

The trial also illustrates the distinction between enrollment and analysis population. Enrollment is listed as 47, while the primary endpoint applies to eligible and evaluable participants. Those populations need not be identical, and the number analyzed is not reported in the record details. Transparent accounting of participants and missing assessments is important for understanding the denominator and the precision of a response estimate.

A single-group phase II design can be useful for describing observed outcomes in a selected population, but it does not create a randomized counterfactual. Without a comparison group, a response rate cannot show what would have occurred under another regimen, nor can it identify the separate effects of the two drugs. That limitation is especially important when readers move from a descriptive finding to a comparative claim.

Finally, the registry distinguishes its primary response endpoint from secondary outcomes and reports selected safety counts. Keeping those outcome types separate is statistically important: tumor response, time-to-event outcomes, and adverse-event summaries answer different questions and have different forms of uncertainty. The record's missing numerical efficacy results mean those distinctions can be explained, but the listed endpoints cannot be treated as established findings.

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 principal limitation for interpreting efficacy is that the registry record does not report the numerical objective response rate or its 95% confidence interval. The primary outcome is defined, but its magnitude and precision are unavailable. Numerical results for the listed secondary outcomes are also not reported in the registry record. This prevents a quantitative account of response, progression-free survival, overall survival, or duration of response.

The study is single-group, with allocation NA and no masking. It therefore has no randomized control arm for comparison. Any outcomes among participants receiving the combination cannot, on their own, establish comparative benefit or harm, and cannot separate the contribution of talazoparib from that of avelumab.

The record lists enrollment of 47, but the primary endpoint population is eligible and evaluable participants. The size of that analysis population, the number of response assessments, the handling of missing assessments, and reasons for any exclusions are not reported in the registry record. These details are needed to understand the denominator and possible effects of missing data.

The registry identifies serious adverse events related to study drugs, other adverse events, and deaths, but the available details do not describe event timing, recurrent events, exposure-adjusted rates, or attribution for deaths. The listed safety counts are not a comparative risk estimate. The registry record also does not report the protocol-level statistical plan, sample-size justification, interim analyses, or multiplicity procedures. These are limitations of the available record; their absence from the record does not establish whether they existed in study documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combination Treatment (Talazoparib Plus Avelumab) for Stage IV or Recurrent Non-Squamous Non-Small Cell Lung Cancer With STK11 Gene Mutation (A LUNG-MAP Treatment Trial) — NCT04173507.
• Registry record last updated 2024-09-03; status last verified 2024-08.
• Results first posted 2023-01-09.
• 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

NCT04173507 is a completed phase II, single-group LUNG-MAP treatment trial sponsored by SWOG Cancer Research Network. It enrolled 47 participants with stage IV or recurrent non-squamous non-small cell lung cancer bearing pathogenic STK11 genomic alterations. Treatment combined daily oral talazoparib with intravenous avelumab on days 1 and 15 of 28-day cycles.

The primary outcome was objective response rate under RECIST 1.1 among eligible and evaluable participants, assessed from registration to progression or treatment discontinuation, up to 1 year and 9 months. The numerical primary result and confidence interval are not reported in the registry record. Secondary outcomes include investigator-assessed progression-free survival, overall survival, duration of response, and treatment-related grade 3 through 5 adverse events.

Safety listings include 15 participants with serious adverse events related to study drugs among 42 at risk, 41 with other adverse events among 42 at risk, and 30 deaths. These are descriptive treatment-group figures, not comparative estimates.