Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy (NCT03626545), a randomized phase 3 study. The primary outcome is Randomized Part: Overall Survival (OS).

2. Clinical Question

The trial was a phase III, randomized, double-blind, placebo-controlled study with quadruple masking and a parallel-group model. Its primary outcome was overall survival in the randomized part. The registry record describes the population as the Full Analysis Set: participants assigned study treatment by randomization.

The main comparison is between the canakinumab-plus-docetaxel group and the placebo-plus-docetaxel group. Because both groups received docetaxel, the contrast addresses the addition of canakinumab within this trial rather than a comparison of docetaxel with no treatment. The study also included a safety run-in, which is distinct from the randomized comparison.

The registry record reports overall survival estimates and a hazard ratio for the randomized groups. It does not report a treatment effect for every other outcome named in the trial description. The primary question should therefore be read as a comparison of the posted overall-survival results, not as a complete account of all outcomes the trial intended to assess.

3. Trial Design

This was a phase III, randomized, double-blind, placebo-controlled, parallel-group study with quadruple masking. It evaluated canakinumab plus docetaxel against placebo plus docetaxel in adults with non-small cell lung cancer previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy. The study title describes use as second- or third-line therapy.

The registry record lists enrollment of 245 and a status of terminated. The study started on 2019-01-23, and primary completion was 2021-01-08. The recorded primary outcome timeframe runs from randomization until death or the final analysis cutoff date of 08-Jan-2021, whichever came first, up to approximately 18 months.

A safety run-in part preceded or accompanied the randomized part in the study record. Its canakinumab-plus-docetaxel description lists docetaxel 75mg/m^2 intravenously and canakinumab 200 mg subcutaneously on Day 1 of each 21-Day cycle, with assessment for at least 2 complete cycles for safety evaluation. The randomized groups received docetaxel 75 mg/m^2 every 3 weeks, alongside either canakinumab or placebo subcutaneously at RP3R. The meaning of RP3R is not reported in the registry record.

For the primary analysis, the registry record identifies the Full Analysis Set in the randomized part as all participants to whom study treatment was assigned by randomization. The posted arm counts for overall survival are 120 for canakinumab plus docetaxel and 117 for placebo plus docetaxel. The record does not explain how these analysis counts relate to the overall enrollment figure or give the reason the study was terminated.

The registry record does not report the original sample-size justification, the planned number of events, or the detailed protocol assumptions used to design the trial. The planning illustrations associated with the posted outcomes are separate from the trial's original design calculations.

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: In the randomized part, a total of 352 subjects were screened. 237 subjects completed the screening phase and were randomized in a 1:1 ratio to treatment with either canakinumab plus docetaxel or placebo plus docetaxel. Three randomized subjects in the placebo plus docetaxel group were not treated

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in the safety run-in part to whom study treatment was assigned, who received at least one dose of any study treatment (including incomplete infusion) and met the minimum exposure criterion and have sufficient safety evaluations, or experienced a DLT during the first 42 days of dosing

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 Randomized Part: Overall Survival (OS), measured over From randomization until death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approximately (approx.) 18 months).

Overall survival measures the time from randomization until death from any cause. For a participant not known to have died by the analysis cutoff, the registry record says the observation was censored at the latest date the participant was known to be alive on or before that cutoff. This makes overall survival a time-to-event outcome: it incorporates both when deaths occurred and the follow-up information available for participants who had not died by the cutoff.

Overall survival is used because it captures death from any cause rather than requiring attribution to a particular disease mechanism or cause. In this study, the Kaplan-Meier method was used to estimate the survival distribution for each randomized group. The reported group summaries are medians: the estimated time by which half of the group’s survival distribution has reached the event. A median is a summary of the distribution, not a description of every participant’s experience.

The comparison also includes a hazard ratio estimated using a log-rank analysis. In general, a hazard ratio compares event rates over follow-up, while the median summarizes the timing of the event distribution. These are different summaries and need not express the evidence in identical ways. Neither provides a complete account of the survival curves or the experience of each participant.

The recorded timeframe ends at the final analysis cutoff date of 08-Jan-2021 or at death, whichever came first, and is described as up to approximately 18 months. Results therefore describe the follow-up available for that analysis, not survival beyond the recorded period.

7. Results Posted in the Registry

• Randomized Part: Canakinumab + Docetaxel vs Randomized Part: Placebo + Docetaxel: hazard ratio 1.06 (95% CI 0.76–1.48), reported p = 0.633 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Overall Response Rate (ORR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Randomized Part: Canakinumab + Docetaxel: 15.0% (18/120) versus 13.7% (16/117) on control; risk difference 1.3 percentage points (95% CI -7.6 to 10.2), risk ratio 1.10 (0.59–2.05); unadjusted two-proportion z-test p = 0.771.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Randomized Part: Canakinumab + Docetaxel and the control. The interval gives the range of effects that remain compatible with the data.

Disease Control Rate (DCR)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Randomized Part: Canakinumab + Docetaxel: 65.8% (79/120) versus 61.5% (72/117) on control; risk difference 4.3 percentage points (95% CI -7.9 to 16.5), risk ratio 1.07 (0.88–1.30); unadjusted two-proportion z-test p = 0.492.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Randomized Part: Canakinumab + Docetaxel and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results give a broadly similar descriptive pattern across response-related outcomes: the point estimates in the randomized groups are close, and the confidence intervals are wide. These outcomes address response and disease control rather than the primary time-to-death question, so they add context but do not replace the overall-survival comparison.

The results for overall response rate and disease control rate do not provide a separate, definitive confirmation of the primary result. Their intervals allow a range of group differences, and no sponsor-reported inferential analyses for these outcomes are listed. The unadjusted re-calculations are not substitutes for a prespecified sponsor analysis and should be read cautiously.

The registry record names additional secondary measures, including duration of response, progression-free survival, time to response, and symptom and quality-of-life outcomes. Numeric results for those measures are not reported in the registry record. Consequently, the full pattern across all intended secondary outcomes cannot be assessed from the posted results.

In general, multiple secondary comparisons increase the chance that some results may appear notable by chance alone, especially when many outcomes are examined without a stated adjustment strategy. The registry record does not report a multiplicity procedure or a hierarchy for secondary testing. These outcomes therefore carry less weight than a clearly prespecified primary analysis and should be viewed as supportive or exploratory rather than as independent proof of a treatment effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Overall Response Rate (ORR)
• Duration of Response (DOR)
• Disease Control Rate (DCR)
• Randomized Part: Progression-Free Survival (PFS)
• Randomized Part: Time to Response (TTR)
• Randomized Part: Time to Definitive 10-point Deterioration (TTD) Symptom Scores of Chest Pain, Cough and Dyspnea Per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Lung Cancer (LC13) Questionnaire
• Randomized Part: Time to Definitive 10-point Deterioration in Global Health Status (GHS)/Quality of Life (QoL), Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire
• Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire

9. Statistical Interpretation

10. Statistical Methods Explained

What does the Kaplan-Meier method estimate?

In general, the Kaplan-Meier method estimates the probability of remaining event-free over time while accounting for participants whose event status is not observed through the end of follow-up. For overall survival, the event is death from any cause. When a participant is not known to have died by the cutoff, the record says follow-up is censored at the latest date the participant was known to be alive on or before the cutoff. Censoring contributes information up to that point; it does not mean that the participant died then.

The registry record says Kaplan-Meier estimates were used for each treatment group and that associated 95% confidence intervals were calculated. The median is read from the estimated survival distribution, not calculated as an average of all observed survival times. The record gives median estimates and their confidence intervals, but it does not provide the survival probabilities at particular time points in this discussion of the outcome description.

What does a hazard ratio mean?

In general, a hazard ratio compares the event hazards between groups over follow-up. A value of 1 corresponds to equal hazards under the ratio interpretation; values above or below 1 indicate different relative hazards in the direction determined by the order of the groups. The reported comparison is canakinumab plus docetaxel versus placebo plus docetaxel, with a hazard ratio of 1.06. This is an estimate, not a direct measure of the difference between the group medians.

The registry record gives the hazard ratio with a 95% confidence interval and a log-rank p-value. The log-rank method compares the event-time experience of the groups while taking account of event timing and censoring. It is not a test of whether the two medians are numerically identical. The record does not report further details about the hazard-ratio model or an assessment of whether its assumptions were met, so those details are not reported in the registry record.

How should the confidence interval and p-value be read?

In general, a confidence interval expresses statistical uncertainty around an estimate using a procedure with a stated coverage level. It is not a range containing a known treatment effect with certainty, and it does not show the probability that the true value lies within the particular interval. The 95% interval for the hazard ratio runs from 0.76 to 1.48. Since it includes 1, the posted interval is compatible with no relative hazard difference as well as with values on either side of that reference.

The reported p-value is 0.633. In general, a p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of an effect. The registry record identifies a log-rank method, but does not report all details of the testing plan.

What is the analysis population?

The primary outcome is reported for the Full Analysis Set in the randomized part, defined in the record as all participants assigned study treatment by randomization. The posted overall-survival arm counts are 120 and 117. This population definition identifies who the analysis is intended to include; it does not by itself disclose whether every randomized participant had complete follow-up or how any deviations were handled. More detailed missing-data and sensitivity-analysis methods are not reported in the registry record.

In general, analysis populations matter because excluding or reclassifying participants after randomization can affect the comparability created by random assignment. The record’s stated population definition is useful, but the detailed disposition of participants and any departures from the stated population are not reported in the registry record. The outcome description does specify censoring at the latest known-alive date for participants not known to have died by the cutoff.

What can secondary outcomes add?

Secondary outcomes can describe other dimensions of disease response, time to progression, symptoms, and quality of life. The registry lists outcomes including overall response rate, duration of response, disease control rate, progression-free survival, time to response, and symptom or quality-of-life deterioration measures. Only overall response rate and disease control rate have numeric results in the posted secondary results. Results for the other listed outcomes are not reported in the registry record.

In general, each additional outcome or comparison creates another opportunity for an apparently notable result to arise by chance. A statistical plan may address this multiplicity through prespecified testing procedures, but those procedures are not reported in the registry record. The absence of a reported adjustment means unadjusted secondary comparisons should be treated as exploratory evidence rather than as independent confirmation of the primary result.

The registry record lists 25 outcome measures and one analysis. It does not explain the relation between those counts and a full prespecified analysis plan, nor does it describe interim analyses or stopping boundaries. Those elements are not reported in the registry record and should not be inferred from the fact that the status is terminated.

11. Confidence Intervals and Precision

The primary hazard-ratio estimate is 1.06, with a 95% confidence interval from 0.76 to 1.48. The interval is important because it shows that the point estimate alone does not capture the uncertainty in the comparison. Values below 1 and above 1 are both compatible with the reported interval, so the estimate does not pin down the direction or magnitude of a relative hazard difference precisely.

The group median estimates are 10.55 months and 11.3 months. Their respective 95% confidence intervals are 8.15 to 12.39 months and 8.54 to 13.8 months. These ranges indicate uncertainty around each group’s estimated median. They should not be treated as participant-level ranges or as a direct confidence interval for the difference between medians. The registry record does not report a confidence interval for a median difference.

In general, precision depends on the amount and distribution of event and follow-up information, not only on the number of people enrolled. The posted randomized analysis counts are 120 and 117, but the registry record does not give the total number of deaths used in the primary analysis. It also does not provide detailed follow-up summaries or the number censored by group, so precision cannot be independently evaluated from those details.

The log-rank p-value of 0.633 is consistent with considerable uncertainty in the treatment comparison, but it should not replace inspection of the estimate and interval. A non-significant p-value does not establish that the groups are equivalent. The confidence interval’s span, the limited recorded follow-up timeframe, and the absence of further sensitivity analyses in the registry record all matter when judging how precisely the primary comparison is resolved.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on fractions of the observed effect, not the trial’s original design calculations. For the primary time-to-event outcome, the figures are total numbers of events, not participants per arm. Under the illustration for 100% of the observed effect, the displayed totals are 9,247 events for 80% power and 12,379 events for 90% power. For 75% of the observed effect, they are 16,439 and 22,007 events; for 50% of the observed effect, they are 36,988 and 49,516 events.

In plain terms, 80% power is the probability of detecting the specified effect under the planning assumptions if that effect is the true one; 90% power is a higher probability target for the same specified effect. Achieving the higher target generally requires more information. The pattern across the listed scenarios also shows that a smaller effect requires more events to detect at the same power target.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For time-to-event outcomes, the calculation uses the Schoenfeld method and reports total events. The effect to detect is the stated fraction of the observed effect. These calculations are not observed power.

The original protocol’s sample-size assumptions and justification are not reported in the registry record. These planning values therefore should not be read as evidence about the trial’s intended enrollment target or as proof that the completed trial was adequately or inadequately sized.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.060, so ln(HR) = 0.0583.
2. d = 4 × (1.96 + 0.842)² / [ln(1.060)]² = 9,246.9, rounded up to 9,247 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.06                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(3626545)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 9,247 (80% power), 12,379 (90% power)
 75% of observed effect: events = 16,439 (80% power), 22,007 (90% power)
 50% of observed effect: events = 36,988 (80% power), 49,516 (90% power)
Simulated power with 9,247 events: 0.797 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The posted primary comparison is the sponsor-reported log-rank analysis: hazard ratio 1.06, 95% confidence interval 0.76 to 1.48, and p-value 0.633. The registry record identifies the estimate as a hazard ratio for canakinumab plus docetaxel versus placebo plus docetaxel. No discrepancy is flagged between the reported result and the recorded comparison.

For this time-to-event outcome, the interpretation uses the sponsor’s reported hazard ratio rather than substituting a simple re-calculation from summary statistics. A hazard ratio depends on event-time and censoring information that cannot be reconstructed from the two median estimates alone. The posted median survival estimates and their confidence intervals provide complementary descriptions, but they do not reproduce the log-rank analysis.

The sponsor’s reported p-value is 0.633. It does not establish that the groups are identical, and the confidence interval’s inclusion of 1 likewise does not establish equivalence. The registry record does not report additional model details, sensitivity analyses, or a fuller statistical analysis plan that would allow a more extensive assessment of the sponsor’s approach.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies overall survival as the primary outcome and lists numerous secondary outcomes, including response, progression, symptoms, and quality-of-life measures. It records 25 outcome measures and one analysis, but does not describe how the outcomes were prioritized in the statistical testing plan. A multiplicity adjustment, a gatekeeping sequence, or another strategy for controlling false-positive findings is not reported in the registry record.

In general, when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. Adjusting for multiplicity can help control that risk, although the appropriate method depends on the prespecified questions and analysis plan. Without a reported strategy, unadjusted secondary comparisons should not be treated as if each were a standalone confirmatory test. The record does not report interim analyses, stopping boundaries, or a plan for interpreting the secondary outcomes alongside the primary result.

For the primary outcome, the stated population is the Full Analysis Set in the randomized part: all participants assigned treatment by randomization. The record does not provide a detailed participant flow, a complete account of missing outcome data, or sensitivity analyses addressing departures from the analysis population. It does specify that participants not known to have died were censored at the latest date they were known to be alive on or before the cutoff.

In general, censoring is appropriate for time-to-event analysis when the assumptions underlying the method are reasonable. The registry record does not report diagnostic checks or additional analyses to evaluate those assumptions. Details of missing data for response, symptom, and quality-of-life outcomes are also not reported in the registry record. These omissions limit assessment of whether missingness could have influenced the secondary findings.

The original sample-size justification, interim analysis plan, and detailed statistical analysis plan are not reported in the registry record. The sample-size illustrations based on observed effects do not fill those gaps and should not be interpreted as evidence of the assumptions used when the trial was designed.

16. 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: pneumonia (25.0%), neutropenia (12.5%), bacterial infection (12.5%), influenza (12.5%), pneumonia pneumococcal (12.5%).

The registry record reports serious adverse events and other adverse events for the on-treatment groups. In the randomized canakinumab-plus-docetaxel group, 55 of 120 participants were recorded as having a serious adverse event, and 111 of 120 were recorded as having other adverse events. In the placebo-plus-docetaxel group, the corresponding counts are 50 of 114 and 109 of 114. These are counts of participants affected among the risk sets recorded for those entries; they are not measures of treatment effect or proof that an event was caused by study treatment.

The record lists pneumonia as a serious adverse-event term at 25.0%, with neutropenia, bacterial infection, influenza, pneumonia pneumococcal, and femur fracture each listed at 12.5%. The denominator and further context for these term percentages are not specified in the adverse-event summary, so they should not be interpreted as rates among all randomized participants without that information.

Deaths are also listed by treatment period, including on-treatment and post-treatment follow-up. These counts do not by themselves identify cause or establish attribution to treatment. The safety run-in and randomized populations are distinct, and their figures should not be combined. Detailed definitions, exposure-adjusted rates, and attribution methods are not reported in the registry record.

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

The primary result describes the overall-survival comparison recorded for the randomized part of this study. Median survival was 10.55 months with canakinumab plus docetaxel and 11.3 months with placebo plus docetaxel. The sponsor-reported hazard ratio was 1.06, with a 95% confidence interval from 0.76 to 1.48 and p-value 0.633. Together, these estimates show that the registry record does not precisely establish a difference between the treatment groups.

The result does not prove that the treatments have identical effects. The confidence interval includes the no-relative-difference value but also allows values on either side of it. A non-significant p-value is not a test of equivalence or non-inferiority. The record does not report a prespecified margin for either type of conclusion.

The result also does not establish that either treatment is beneficial or ineffective in clinical practice. It is a statistical comparison in the recorded trial population, under the study conditions and follow-up available to the analysis cutoff. It does not supply an individual prediction, establish what would happen beyond the observed follow-up, or resolve the effects of treatment in populations not described by this trial.

The response-related secondary results provide additional descriptive information, but the registry record does not report sponsor inferential analyses for them. Other outcomes named in the registry, including progression-free survival and symptom or quality-of-life measures, do not have numeric results reported there. The overall evidence should therefore be interpreted primarily through the posted primary analysis, with the available secondary outcomes treated as limited supporting context.

Finally, the study status is terminated, but the reason is not reported in the registry record. Termination alone does not explain the result or establish a safety, efficacy, or feasibility reason for ending the study. A fuller interpretation would require information about the protocol, analysis plan, participant disposition, and the context of termination that is not reported in the registry record.

18. Why This Trial Matters Statistically

This trial illustrates why a time-to-event result should be read through its estimate and uncertainty rather than by looking only at the median values or the p-value. The two group medians are not far apart descriptively, but the hazard ratio and its confidence interval summarize a comparison across event times and show substantial uncertainty about the relative hazard.

It also demonstrates the distinction between absence of statistically persuasive evidence for a difference and evidence that two treatments are equivalent. The reported confidence interval spans values below and above 1, while the log-rank p-value is 0.633. Neither alone establishes that the groups have the same survival experience. Clear interpretation depends on stating what range of effects remains compatible with the data.

The registry record also highlights limits of interpreting secondary outcomes when the testing strategy is not documented. Response and disease-control findings may complement an overall-survival analysis, but multiple unadjusted comparisons can be less conclusive than a prespecified primary test. Results for several other named outcomes are not reported in the registry record, leaving the broader outcome picture incomplete.

Finally, planning calculations based on an observed effect are not a substitute for the original trial design assumptions. They illustrate the information that would be required to detect specified fractions of the observed effect under stated planning conditions, while the original sample-size justification is not reported. Keeping these distinctions clear helps prevent post hoc planning illustrations from being mistaken for evidence that the trial was designed around its observed result.

19. 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 gives a final analysis cutoff of 08-Jan-2021 and describes the primary outcome timeframe as up to approximately 18 months. The results therefore have a limited recorded follow-up horizon. The record does not give detailed follow-up distributions or the number of deaths contributing to the primary analysis, which restricts assessment of the amount of time-to-event information available.

The study status is terminated, but the reason is not reported in the registry record. Without that context, termination should not be attributed to efficacy, safety, recruitment, or another cause. The overall enrollment figure is 245, while the primary randomized analysis counts are 120 and 117; the record does not explain the relationship between those numbers or provide a full participant disposition.

The protocol’s original sample-size assumptions and justification are not reported. Nor are detailed interim-analysis methods, a full multiplicity strategy, hazard-ratio model details, or sensitivity analyses for the primary outcome. These gaps limit assessment of design assumptions and robustness.

Although several secondary outcomes are named, numeric results are posted for only some of them in the registry record. The sponsor’s inferential analyses for the response-related outcomes are not listed. Missing-data methods for those outcomes and detailed adverse-event attribution and exposure information are also not reported. These limitations mean the registry results support a focused reading of the posted primary comparison, rather than a complete evaluation of every planned endpoint or the full safety profile.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy — NCT03626545.
• Registry record last updated 2023-08-21; status last verified 2023-08.
• Results first posted 2023-06-22.
• 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.

23. Record Summary

NCT03626545 is a phase III, randomized, double-blind, placebo-controlled study of canakinumab plus docetaxel versus placebo plus docetaxel in adults with previously treated non-small cell lung cancer. The registry record lists enrollment of 245 and status as terminated.

The primary outcome was overall survival in the randomized part. Median estimates were 10.55 months and 11.3 months; the reported hazard ratio was 1.06, with a 95% confidence interval from 0.76 to 1.48 and p-value 0.633. The record also posts response-related secondary results, while results for several other named outcomes are not reported in the registry record.

The record does not report the reason for termination, the original sample-size justification, or a full statistical analysis plan. Interpretation is therefore limited to the posted estimates, methods, population definition, and follow-up cutoff.