PCSK9 Inhibitor and PD-1 Inhibitor in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PCSK9 Inhibitor and PD-1 Inhibitor in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung (NCT05553834), a na phase 2 study. The primary outcome is Number of Participants With a Complete or Partial Response (PR) Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 Criteria.

2. Clinical Question

The registry’s rationale is that PCSK9 may contribute to resistance to immune checkpoint blockade by reducing tumor-cell surface MHC class 1 molecules. The study evaluates whether combining PCSK9 inhibition with PD-1 inhibition can generate anti-tumor activity and clinical responses in this setting. That rationale is the motivation for the trial, not evidence that the proposed biological process or clinical effect occurred in participants.

The primary outcome is a count of participants with complete or partial response, not a comparison of response between randomized groups. The registry also lists adverse events, progression-free survival under RECIST 1.1, and overall survival as secondary outcomes. The record does not report outcome analyses, so it does not answer whether participants experienced responses or how long outcomes lasted.

3. Trial Design

This is a Phase II, single-group study sponsored by Duke University. The intervention is the combination of alirocumab and cemiplimab. The registry lists enrollment as 60 and status as active, not recruiting. It records a start date of 2023-05-16 and a primary completion date of 2025-09-16. These record entries describe the study, but do not establish how many participants received treatment or completed follow-up.

Allocation is listed as NA, masking as none, and the model as single group. Thus, the record describes an open-label study without a concurrent control group. The response outcome is assessed among participants who received at least one dose of both alirocumab and cemiplimab. The stated assessment period begins on Day 1 of treatment and continues until documented progression or death, whichever comes first, with assessment up to 110 weeks per RECIST 1.1.

The absence of a randomized control group matters for interpretation. A response count in a single group can describe outcomes in treated participants, but by itself cannot estimate how outcomes would have differed under another treatment or no study treatment. Differences from other studies would not constitute a like-for-like comparison because participant characteristics, follow-up, and other study features may differ.

The registry lists four outcome measures and no analyses. It does not report the protocol’s planned statistical analysis, a sample-size justification, interim analyses, or a prespecified comparator. The planning illustrations associated with the posted material are not evidence of the trial’s own design rationale; they use hypothetical two-arm assumptions and should not be read as observed power or as the study’s registered analysis plan.

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

Analysis population for the primary outcome, as defined in the registry: Participants who received at least one dose of alirocumab and cemiplimab.

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 Number of Participants With a Complete or Partial Response (PR) Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 Criteria, measured over Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks per RECIST 1.1.

The primary endpoint is the number of participants with a complete or partial response according to RECIST 1.1. The registry describes a partial response as at least a 30% decrease in the sum of the longest diameters of target tumors compared with the baseline measurement. The record does not give the criteria for complete response in its endpoint description, so further details of that classification are not reported in the registry record.

Response is used in oncology trials as a structured way to describe measurable change in target tumors. RECIST provides standardized criteria for categorizing response, which can make outcome assessment more consistent than an informal judgment of improvement. A count of participants meeting response criteria is a binary outcome at the participant level: each participant either meets the stated complete-or-partial-response definition or does not.

The endpoint is assessed from treatment Day 1 until the first documented progression or death, whichever comes first, up to 110 weeks. This time frame defines when response is evaluated; it does not mean that all participants had the same follow-up duration. The record does not report the observed number of participants with response, an estimated response proportion, or uncertainty around such an estimate. Accordingly, the endpoint definition is available, but its result is not reported in the registry record.

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 observed among participants who receive the study intervention. For a binary response endpoint, the basic descriptive result is the number of participants meeting the response definition, together with the number assessed. Such a result can describe the observed group. Without a concurrent control arm, it does not directly estimate a treatment contrast, because there is no randomized group showing what would have occurred under an alternative condition.

This distinction is especially important when the question is causal. A response after treatment is not, on its own, proof that the treatment caused the response. Disease course, participant selection, prior therapies, assessment practices, and other factors may influence the observed outcome. Random assignment can help balance such influences across groups; this registry record describes no random allocation or control arm.

How should a response count be understood?

The primary outcome is a participant-level classification based on RECIST 1.1. The registry defines the endpoint as the number with complete or partial response and gives a partial-response criterion based on change from baseline in target-tumor measurements. In statistical terms, this is a binary outcome for each participant. A count is informative only alongside a clear analysis population and information about how many participants were assessed. The record specifies the population as those receiving at least one dose of both agents, but does not report the response count or analysis results.

For binary outcomes, an estimated proportion can be accompanied by a confidence interval to communicate sampling uncertainty. In general, a confidence interval expresses a range of values compatible with the observed data under the method’s assumptions; it does not guarantee that the true value lies in that interval. No response proportion or interval is reported in the registry record.

What does the follow-up window establish?

The response assessment period begins on treatment Day 1 and ends at the first documented progression or death, whichever comes first, with assessment up to 110 weeks. This specifies the endpoint’s intended time frame. It does not show whether all participants were followed for the same duration, whether assessments occurred on schedule, or how missing assessments were handled. Those details are not reported in the registry record.

Progression-free survival and overall survival are also listed as secondary outcomes. These are time-to-event outcomes, for which interpretation usually depends on defining the event, the time origin, censoring, and follow-up. A survival curve can describe the estimated probability of remaining event-free over time, while a confidence interval expresses uncertainty in that estimate. The registry record lists the outcomes but does not report their results or the analysis methods, including censoring rules.

What do the planning illustrations mean?

The planning illustrations are based on an assumed two-arm comparison, equal allocation, a two-sided significance level of 0.05, and a normal approximation. They describe hypothetical planning for a stated fraction of an observed effect. For time-to-event outcomes, the stated planning approach uses total events; for other outcomes, it uses participants per arm. These assumptions do not describe the registered single-group design and are not evidence of the study’s sample-size justification.

Planning calculations ask how much information a hypothetical study might need under specified assumptions. They are not observed power, and they do not show that a planned study has found an effect. Since the registry record does not report a design justification or the values used in the illustrations, those calculations cannot be treated as the trial’s prespecified target or as a substitute for its results.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion means the observed variability is greater than the model expects. If ignored, standard errors may be too small and uncertainty may be understated. This is a general statistical consideration, not a claim about this study: the registry record does not report an analysis of count outcomes or whether over-dispersion was assessed.

More broadly, the registry record does not identify a statistical model for the primary endpoint, explain how missing outcome assessments were handled, or report adjustment for multiple outcomes. These absences prevent a detailed appraisal of analysis choices. The endpoint definition can be described, but the analysis plan and estimates needed to judge statistical precision are not reported in the registry record.

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("Experimental: Alirocumab and Cemiplimab")
n      <- c(58)
events <- c(5)
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  Experimental: Alirocumab and Cemiplimab  58  5  8.6  2.9  19.0  3.7  18.6  3.8  18.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary response outcome and secondary outcomes covering adverse events, progression-free survival, and overall survival. Testing or estimating several outcomes raises questions about multiplicity: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. Statistical plans may address this through a hierarchy of outcomes or adjustments, but no approach is reported in the registry record. The record also does not report whether interim analyses were planned or conducted.

Missing data can affect both the number of participants included in an analysis and the interpretation of an estimate. For response, relevant details would include how participants without an evaluable scan were classified, whether assessments were missed, and what happened after treatment discontinuation. The registry identifies the primary population as participants who received at least one dose of both drugs, but does not report the analysis population size, the number assessed, or a missing-data method.

For progression-free and overall survival, assessment of follow-up and censoring would be important. The registry lists these outcomes but does not report the number of events, follow-up completeness, censoring rules, or analysis results. It is therefore not possible to evaluate the effects of missing assessments or incomplete follow-up from the registry record.

These limitations do not establish that an analysis was absent from the study’s protocol or other documents. They mean only that multiplicity procedures, interim analyses, missing-data methods, and detailed analysis populations 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nervous system disorders - other, specify (5.0%), pleural effusion (5.0%), hypotension (5.0%), atrial fibrillation (3.3%), sinus tachycardia (3.3%).

The safety summary lists 60 participants at risk for serious adverse events and 60 at risk for other adverse events. It records 29 participants affected by serious adverse events and 56 affected by other adverse events. The record also lists 48 deaths. These are distinct summary fields; they should not be added together or treated as mutually exclusive groups. A participant may experience more than one event, and the record does not provide enough detail to reconstruct event-level patterns or timing.

Among the listed serious adverse event terms, nervous system disorders - Other, specify, pleural effusion, and hypotension are each reported as 5.0%. Atrial fibrillation, sinus tachycardia, and adrenal insufficiency are each reported as 3.3%. These percentages describe the registry’s listed terms; the record does not provide term-specific participant counts in the registry record for this explanation. The figures do not establish that an event was caused by treatment.

Serious adverse events are not synonymous with all adverse events, and the count of participants affected is not necessarily the count of individual event episodes. The registry figures do not report severity grading beyond the serious classification, duration, resolution, treatment attribution, or a comparison group. The single-group design offers no randomized safety comparison. The death count is a safety summary, not an explanation of causes or evidence of treatment-related mortality.

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

The registry record establishes that a Phase II, single-group study is evaluating alirocumab with cemiplimab in metastatic non-small cell lung cancer after progression on prior anti-PD-1 therapy. It defines a primary endpoint based on complete or partial response under RECIST 1.1 and lists safety, progression-free survival, and overall survival outcomes. Those details clarify what the study is intended to assess.

The record does not report the response outcome or analyses. It therefore does not establish whether any participant had a complete or partial response, how often response occurred, or how precisely an effect was estimated. It also does not provide results for progression-free survival or overall survival. The safety entries describe recorded adverse-event summaries, but do not establish causation, comparative risk, or the circumstances of the deaths.

Even a reported response count in this design would be descriptive rather than a randomized estimate of benefit relative to another treatment. With no concurrent comparator, differences from an external group could reflect differences in participants, follow-up, assessment, or other features. Because alirocumab and cemiplimab are given together, the design also cannot isolate the contribution of either component.

The statistical planning illustrations do not change these limits. They rely on hypothetical two-arm assumptions and are planning calculations, not observed study results or observed power. They cannot fill the gap left by the absence of an efficacy analysis in the registry record.

Consequently, the record supports a description of the study question, design, outcome definitions, and posted safety figures. It does not support a conclusion about treatment effectiveness, comparative safety, or clinical value. Those conclusions require outcome analyses and the context needed to assess uncertainty and bias.

14. Why This Trial Matters Statistically

This trial addresses a defined clinical research question in metastatic non-small cell lung cancer after progression on prior anti-PD-1 therapy. Its biological rationale links PCSK9 with immune checkpoint blockade resistance, and the intervention combines an anti-PCSK9 antibody with an anti-PD-1 antibody. The registry’s response endpoint provides a structured way to assess measurable tumor response in the study population.

Statistically, the design is important to distinguish from a comparative trial. A single-group study can document outcomes among treated participants, but it cannot directly estimate a randomized contrast. Recognizing that distinction prevents descriptive response or safety figures from being misread as proof that the combination caused an outcome or performed better than another option.

The record also illustrates why outcome definitions and results are different kinds of information. The RECIST 1.1 endpoint and assessment window specify what the study intends to measure, while the absence of a posted analysis means the observed response and its precision remain unknown from the record. Likewise, the listed safety counts are useful descriptive information, but without attribution details and a comparator they do not quantify relative risk.

Finally, planning assumptions should be separated from both design and evidence. The planning illustrations use hypothetical two-arm assumptions, whereas the registered study is single group. Keeping that distinction clear helps readers avoid interpreting planning calculations as proof of statistical power or as results. The trial matters as a study of a specified combination and population, while the currently reported registry information does not answer its efficacy question.

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 outcomes is that no efficacy analyses are reported in the registry record. There is no posted response count, response estimate, or confidence interval. Although the primary endpoint and its assessment period are defined, the record does not show how many participants were evaluable or how many had missing response assessments.

The single-group, unmasked design also limits causal and comparative interpretation. Without a concurrent randomized control arm, outcomes cannot be directly contrasted with outcomes under an alternative treatment. Lack of masking may also be relevant to outcome assessment and reporting, but the registry record does not describe assessment safeguards or independent review.

The combination regimen prevents attribution of an observed outcome to either drug separately. The record does not report treatment exposure, adherence, dose changes, or discontinuations, so these factors cannot be considered in interpreting the listed outcomes. It also does not report details of participant characteristics beyond the disease setting and prior-treatment context stated in the study description.

Safety information is limited to summary counts and selected serious adverse event terms. Timing, severity grading beyond seriousness, treatment attribution, event resolution, and causes of death are not reported in the registry record. There is no comparison group for assessing relative safety.

Finally, analysis details are not reported: the sample-size justification, statistical model, multiplicity procedure, interim analyses, missing-data approach, and survival-analysis methods are not available in the record. The planning illustrations use assumptions that do not match the registered single-group design. These gaps constrain assessment of precision, bias, and how closely any future results would answer the registered question.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PCSK9 Inhibitor and PD-1 Inhibitor in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung — NCT05553834.
• Registry record last updated 2026-11-04; status last verified 2026-10.
• Results first posted 2026-11-04.
• 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

NCT05553834 is a Phase II, single-group study sponsored by Duke University. It evaluates alirocumab plus cemiplimab in metastatic non-small cell lung cancer after progression on first-line immune checkpoint blockade. The registry lists enrollment as 60, status as active, not recruiting, and no masking.

The primary outcome is the number of participants with complete or partial response under RECIST 1.1 among those who received at least one dose of both agents. The stated assessment period is from treatment Day 1 until documented progression or death, whichever comes first, assessed up to 110 weeks. Secondary outcomes include adverse events, progression-free survival, and overall survival.

The record reports safety summaries but no outcome analyses. It does not report an efficacy result, a statistical analysis plan, a sample-size justification, or methods for multiplicity and missing data. The single-group design provides no randomized comparator.