Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC) (NCT04644237), a randomized phase 2 study. The primary outcome is Percentage of Participants With Confirmed Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer.

2. Clinical Question

3. Trial Design

This was a phase 2, multicenter, randomized, double-masked, parallel-group study of trastuzumab deruxtecan in HER2-mutated metastatic non-small cell lung cancer. The registry lists enrollment of 152 participants and two randomized groups: 5.4 mg/kg and 6.4 mg/kg, each administered by intravenous infusion every 3 weeks. The registry record is marked completed. The recorded study start was 2021-03-19, and primary completion was 2022-12-23.

The study population had disease recurrence or progression during or after at least one prior anticancer regimen, second line or later, that included platinum-based chemotherapy. The primary analysis population was the Full Analysis Set, defined in the record as all subjects for whom study treatment was assigned by randomization. The primary outcome timeframe was 9 months after the last participant was randomized to data cut off, up to approximately 21 months. Investigator-assessed response and other secondary outcomes had a timeframe of 9 months after the last participant was randomized or later to data cut off, up to approximately 35 months.

The registry describes masking as double, but does not report which trial roles were masked or the operational details of masking. The randomization method, allocation ratio, and concealment procedures are not reported in the registry record. The record lists 13 outcome measures and indicates 12 secondary outcomes posted. It does not report the original sample-size justification or the trial’s prespecified statistical analysis plan. The active-dose design means the primary comparison concerns two doses of the same intervention; it cannot directly estimate a difference between trastuzumab deruxtecan and no treatment or another therapy.

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: Full Analysis Set includes all subjects for whom study treatment was assigned by randomization

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: The baseline demographic characteristics were assessed in the Full Analysis Set.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Confirmed Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer, measured over 9 months after the last participant is randomized to data cut off, up to approximately 21 months.

The primary endpoint was the percentage of participants with a confirmed objective response, assessed by blinded independent central review. A response was defined as complete response or partial response using RECIST version 1.1. A complete response meant disappearance of all target lesions; a partial response meant at least a 30% decrease in the sum of target-lesion diameters. The response was therefore a binary participant-level outcome: each participant either met the confirmed-response definition or did not.

Response is used in oncology trials to describe whether tumors meet defined criteria for shrinkage or disappearance during follow-up. General statistical context: a proportion is straightforward to interpret as the share of participants meeting the endpoint, but it does not describe how long a response lasts or whether participants live longer. Those questions require other outcomes, such as duration of response and overall survival, which are listed separately among this study’s outcomes.

Central review provides an assessment separate from the investigator assessment, and masking is intended to reduce the influence of knowledge about treatment assignment on outcome evaluation. The registry specifies blinded independent central review for the primary endpoint. It does not report further details about review procedures, confirmation timing, or how missing response assessments were handled.

7. Results Posted in the Registry

• Trastuzumab Deruxtecan 6.4 mg/kg: 56.0% (28/50) versus 50.0% (51/102) on control; risk difference 6.0 percentage points (95% CI -10.8 to 22.8), risk ratio 1.12 (0.82–1.53); unadjusted two-proportion z-test p = 0.487.

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.

Percentage of Participants With Confirmed Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung CancerTumors

• 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:
  • Trastuzumab Deruxtecan 6.4 mg/kg: 56.0% (28/50) versus 46.1% (47/102) on control; risk difference 9.9 percentage points (95% CI -6.9 to 26.7), risk ratio 1.22 (0.88–1.68); unadjusted two-proportion z-test p = 0.250.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Trastuzumab Deruxtecan 6.4 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer

• 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:
  • Trastuzumab Deruxtecan 6.4 mg/kg: 88.0% (44/50) versus 90.2% (92/102) on control; risk difference -2.2 percentage points (95% CI -12.9 to 8.5), risk ratio 0.98 (0.86–1.10); unadjusted two-proportion z-test p = 0.679.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Trastuzumab Deruxtecan 6.4 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Trastuzumab Deruxtecan 6.4 mg/kg: 2.0% (1/50) versus 2.0% (2/101) on control; risk difference 0.0 percentage points (95% CI -4.7 to 4.8), risk ratio 1.01 (0.09–10.87); unadjusted two-proportion z-test p = 0.993.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Trastuzumab Deruxtecan 6.4 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several distinct questions: response assessed by investigators, disease control, duration of response, progression-free survival, overall survival, treatment-emergent adverse events, pharmacokinetic measures, and anti-drug antibodies. The registry also lists other secondary outcome measures. This breadth is useful for describing different aspects of tumor response, follow-up, safety, and drug exposure, but the outcomes do not all measure the same thing and should not be combined into one overall conclusion.

At a broad level, the investigator-assessed response results point in the same direction as the central-review primary estimate, while disease-control estimates do not show a higher proportion in the higher-dose group. These observations do not resolve the primary uncertainty. Investigator and central assessments use different assessors, and disease control is a broader endpoint than confirmed objective response. Neither can substitute for the primary endpoint or establish that a dose is superior.

General statistical context: secondary outcomes are often useful for exploring consistency and describing additional effects, but they carry less inferential weight when a prespecified testing order and multiplicity control are not reported. If many outcomes are tested, some results can appear notable by chance. The registry record does not report a multiplicity procedure or a hierarchy governing confirmatory claims. The unadjusted secondary comparisons should therefore be treated as descriptive and hypothesis-generating rather than as independent proof.

The registry lists time-to-event outcomes and safety outcomes, but their interpretation depends on follow-up, event definitions, censoring, and analysis methods. Those details are not reported in the results summarized in the registry record. The posted secondary response and disease-control estimates provide context alongside the primary result; they do not negate the broad uncertainty in the dose comparison.

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

• Percentage of Participants With Confirmed Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung CancerTumors
• Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
• Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
• Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
• Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
• The Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
• Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
• Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a

9. Statistical Interpretation

10. Statistical Methods Explained

The main outcome is binary at the participant level: confirmed response or no confirmed response. For a binary outcome, the response proportion is the number of participants meeting the endpoint divided by the relevant analysis denominator. The registry gives response percentages and 95% confidence intervals for each dose group. It does not state the statistical method used to construct those intervals, so no particular interval procedure should be inferred.

What does the between-group comparison express?

The posted comparison is a risk difference, which expresses the difference between the two groups’ response proportions on the proportion scale. A value above zero would indicate a higher response proportion in the 6.4 mg/kg group under the comparison’s coding; a value below zero would indicate a higher proportion in the 5.4 mg/kg group. The reported point estimate is 0.06, with a 95% confidence interval that crosses zero. The interval therefore includes values consistent with either direction of difference. The posted unadjusted p-value is 0.487.

General statistical context: a confidence interval describes a range of values reasonably compatible with the data under the method used. It is not a guarantee that the true value lies in the interval, and it does not assign probabilities to individual values after the data are observed. When an interval for a difference includes zero, the data do not clearly distinguish a positive difference from no difference or a negative difference at the chosen confidence level. That does not prove there is no difference.

Why use a central response assessment?

The primary endpoint was evaluated by blinded independent central review, while a secondary response outcome was assessed by investigators. General statistical context: separating assessment from direct treatment decisions can help limit some forms of assessment bias, and masking can reduce the chance that expectations influence judgments. The registry identifies the central review as blinded and independent, but does not describe its procedures in more detail. The central and investigator assessments should be recognized as distinct endpoints rather than treated as identical measurements.

What is the analysis population?

The Full Analysis Set includes all subjects for whom study treatment was assigned by randomization, according to the registry definition. The primary result is therefore described using the randomized assignment population, not a population defined by completing treatment. The registry does not report additional details about exclusions from the Full Analysis Set or the handling of participants whose response status could not be determined.

General statistical context: keeping participants in the group to which they were randomized helps preserve the advantages of random assignment. However, the practical interpretation still depends on how post-randomization events, missing measurements, and protocol deviations are handled. Those details are not reported in the registry record and should not be assumed.

What do the confidence intervals and p-value contribute?

The response percentages describe the observed results, while the confidence intervals indicate their uncertainty. The p-value addresses a test of no difference in the unadjusted comparison. These measures answer related but different questions: an estimate gives the direction and size of the observed contrast, an interval conveys precision and plausible values, and a p-value summarizes compatibility with a particular null model. None alone gives the clinical importance of a difference.

The record also includes risk-ratio and odds-ratio comparisons in its posted comparison data. General statistical context: a risk ratio compares proportions as a ratio, whereas an odds ratio compares odds. Those scales can be less directly intuitive than absolute proportions, especially when outcomes are common. The primary interpretation can remain anchored in the reported percentages and the risk-difference comparison. The registry does not report an adjusted model for the primary result.

There are multiple outcomes, including response assessed in different ways, disease control, time-to-event outcomes, safety outcomes, pharmacokinetic measurements, and anti-drug antibodies. General statistical context: examining multiple outcomes creates multiple opportunities for apparently notable results, so interpretation depends on whether outcome priorities and multiplicity procedures were prespecified. The registry record does not report a multiplicity adjustment or a hierarchy for the secondary outcomes.

11. Confidence Intervals and Precision

The primary response estimate was 50.0% in the 5.4 mg/kg group, with a 95% confidence interval from 39.9% to 60.1%. In the 6.4 mg/kg group, it was 56.0%, with a 95% confidence interval from 41.3% to 70.0%. These intervals are wide enough to leave meaningful uncertainty around each group’s response proportion. The interval for the between-group risk difference crosses zero, so the comparison is compatible with either direction of difference as well as no difference.

The 6.4 mg/kg group had fewer participants in the primary outcome results than the 5.4 mg/kg group, and its response interval is wider. General statistical context: estimates based on fewer participants tend to be less precise when other factors are similar, because the observed proportion can vary more from sample to sample. A confidence interval communicates that sampling uncertainty; it does not account for every possible source of uncertainty, such as measurement limitations or unreported missing-data decisions.

The point estimates differ, but precision matters when interpreting that difference. The unadjusted p-value of 0.487 does not offer strong evidence against a no-difference model, while also not establishing that the doses are equivalent. The registry does not report an equivalence margin, a noninferiority margin, or a precision target for the primary comparison. As a result, the interval should be read as an indication of substantial uncertainty, not as confirmation of a particular dose relationship.

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 planning figures are participants per arm, not total event counts. They are illustrations based on the observed effect, not the original trial design assumptions; the original sample-size justification is not reported in the registry record. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect.

The 80% power column represents the number of participants per arm in a hypothetical design that would have an 80% chance of detecting the specified effect under those assumptions, if the assumed effect and statistical model were correct. The 90% power column uses a higher target chance of detecting that effect and therefore generally calls for more participants per arm. These figures are planning illustrations, not observed power.

For the primary comparison, planning for 100% of the observed effect gives 1,086 participants per arm for 80% power and 1,453 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,933 participants per arm for 80% power and 2,588 participants per arm for 90% power. Planning for 50% of the observed effect gives 4,356 participants per arm for 80% power and 5,831 participants per arm for 90% power. The pattern reflects a general principle: smaller effects are harder to distinguish from random variation, so detecting them requires more participants under otherwise similar assumptions.

These calculations should not be read as evidence that the trial was designed for those sample sizes, or as evidence about the probability that its observed result is correct. They describe hypothetical future planning under specified assumptions. They also inherit uncertainty from using an observed effect as the basis for planning; an observed effect can differ from the effect that would be seen in another study.

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

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.500; treatment proportion p₁ = 0.560; average p̄ = 0.530.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7058 = 1.3834.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.7046 = 0.5930.
4. n = (1.3834 + 0.5930)² / (0.0600)² = 1,085.0, rounded up to 1,086 participants per arm 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
p0 <- 0.5                          # control proportion
p1 <- 0.56                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4644237)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,086 (80% power), 1,453 (90% power)
 75% of observed effect: n per arm = 1,933 (80% power), 2,588 (90% power)
 50% of observed effect: n per arm = 4,356 (80% power), 5,831 (90% power)
power.prop.test: 1085 
Simulated power at n = 1,086 per arm: 0.805 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The study has a primary response endpoint and multiple secondary outcomes spanning response, disease control, time-to-event outcomes, adverse events, pharmacokinetics, and anti-drug antibodies. The registry record does not report a statistical testing hierarchy, a multiplicity adjustment, or a plan for controlling the chance of false-positive findings across the outcomes. The reported secondary comparisons are unadjusted. They should therefore be interpreted cautiously, particularly if used to make claims beyond the primary endpoint.

Missing-data handling is also not reported in the registry record. The Full Analysis Set is defined as all subjects for whom treatment was assigned by randomization, but the record does not specify how participants without an evaluable response assessment were treated, whether any imputation was used, or whether sensitivity analyses assessed alternative assumptions. The outcome denominators in the posted results are not identical across every measure, and the record does not explain all denominator differences. No reason for a missing assessment should be inferred from those counts.

The primary timeframe is stated as 9 months after the last participant was randomized to data cut off, up to approximately 21 months. The record does not give further details about the data-cutoff process or the handling of assessments outside the specified window. It does not report interim analyses, stopping rules, or a prespecified statistical analysis plan. These omissions limit assessment of whether the analysis choices were set before results were examined.

These are reporting limitations, not proof that the study lacked appropriate procedures. The registry record alone does not establish whether additional plans or analyses existed elsewhere. Without the missing details, readers cannot fully assess multiplicity control, missing-outcome assumptions, or the extent to which the posted estimates follow a prespecified analysis.

15. 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 (6.0%), anaemia (4.0%), fatigue (4.0%), general physical health deterioration (4.0%), malaise (4.0%).

For serious adverse events, the registry lists 42 participants among 101 at risk in the 5.4 mg/kg group and 26 among 50 at risk in the 6.4 mg/kg group. The listed at-risk denominators are the ones recorded for this safety outcome; they are not the same as the randomized counts in the primary response results. The record does not explain the denominator differences.

The most frequently listed serious-event terms include pneumonia at 6.0%, and anaemia, fatigue, general physical health deterioration, malaise, and neutrophil count decreased at 4.0% each. The record also lists other adverse events affecting all 101 participants at risk in the lower-dose group and all 50 at risk in the higher-dose group. Deaths are listed for 52 and 24 participants, respectively. These counts alone do not establish the cause of an event or whether it was attributed to study treatment. The registry record does not provide additional context about timing, duration, attribution, or comparative safety analysis.

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

The primary result describes confirmed response proportions in two randomized dose groups. The observed proportions were numerically higher in the 6.4 mg/kg group, but the confidence intervals are broad, the between-group interval crosses zero, and the unadjusted p-value is 0.487. Together, these results do not provide strong statistical evidence of a difference between the doses. They also do not show that the doses are equivalent or that no meaningful difference exists.

The endpoint is tumor response assessed according to RECIST version 1.1. It does not, by itself, establish the duration of response, progression-free survival, overall survival, or the balance of benefits and harms. Those are separate outcomes. The registry lists several of them, but the response result should not be used as a substitute for their results or as a complete summary of the study.

General statistical context: statistical evidence and clinical importance are different questions. A numerical difference can be uncertain, and a small p-value, if observed, would not by itself determine whether a difference matters to patients. Judging clinical importance requires an interpretation of the endpoint, the size and precision of the effect, other outcomes, and the study context. The registry record does not report a threshold for a clinically important difference in response.

The study compares two active doses in a selected population with HER2-mutated metastatic NSCLC previously treated with a platinum-containing regimen. It cannot establish a comparison with placebo or another treatment. Its results should be interpreted within the population, endpoint, and follow-up described in the record, with the limitations around missing-data methods and multiplicity kept in view.

17. Why This Trial Matters Statistically

This trial raises a useful statistical question about comparing doses of the same intervention when the primary endpoint is a participant-level response proportion. The estimate is easy to understand as a percentage, but a numerical difference between groups must be read alongside its uncertainty. Here, the confidence intervals are broad and the unadjusted comparison does not clearly distinguish the doses. That contrast between a visible point-estimate difference and imprecise evidence is an important lesson in interpreting clinical results.

The study also illustrates why endpoint assessment matters. The primary outcome used blinded independent central review, while a secondary response outcome used investigator assessment. These are related but distinct measurements. Comparing them can help readers consider whether the general response pattern is consistent, while recognizing that differences in assessment can affect results.

Finally, the record demonstrates the value of separating observed results from planning calculations. The planning illustrations describe hypothetical participant requirements under stated assumptions; they do not reveal the trial’s original design rationale or its achieved power. Likewise, the presence of several secondary outcomes does not make each unadjusted comparison confirmatory. A clear reading depends on keeping the primary endpoint, precision, analysis population, and limitations distinct.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the original sample-size justification, the randomization method, or the allocation ratio. It also does not give operational details about masking or the procedures used for central review. Those omissions limit readers’ ability to assess design and outcome-assessment procedures in depth.

The primary endpoint result has uncertainty, and the smaller 6.4 mg/kg group has a wider response interval. The registry does not explain the difference between the randomized group counts and the outcome denominators used for safety reporting. It also does not report how missing or unevaluable response assessments were handled, or provide sensitivity analyses for missing data.

Several secondary outcomes are listed, but the record does not report a multiplicity strategy or analysis hierarchy. The unadjusted comparisons should not be treated as a set of confirmatory findings. The registry also does not report the detailed methods for time-to-event analyses, including censoring and event-handling procedures, or a full analysis plan. Follow-up timeframes differ across primary and secondary outcomes, which matters when interpreting outcome-specific estimates.

These limitations concern what can be established from the registry record. They do not prove that relevant methods were absent from the study; they mean that those methods are not reported in the registry record and therefore cannot be assessed from it.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC) — NCT04644237.
• Registry record last updated 2025-11-21; status last verified 2025-11.
• Results first posted 2024-01-30.
• 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.

22. Record Summary

NCT04644237 is a completed, randomized, double-masked, parallel-group phase 2 study of trastuzumab deruxtecan in HER2-mutated metastatic non-small cell lung cancer. It enrolled 152 participants and compared intravenous doses of 5.4 mg/kg and 6.4 mg/kg every 3 weeks in people whose disease had recurred or progressed after at least one prior anticancer regimen including platinum-based chemotherapy.

The primary endpoint was confirmed objective response assessed by blinded independent central review using RECIST version 1.1. The posted response estimates were 50.0% for 5.4 mg/kg and 56.0% for 6.4 mg/kg, with broad 95% confidence intervals. The unadjusted comparison does not provide strong evidence of a difference between doses, and does not establish equivalence. Important details about the original sample-size rationale, multiplicity, and missing-data handling are not reported in the registry record.