This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. The numerical trial information on this page is restricted to the ClinicalTrials.gov record. No additional efficacy estimates, confidence intervals, p-values, or publication results have been added.
1. Trial at a Glance
DESTINY-Lung02 was a randomized, double-blind, parallel phase 2 trial evaluating trastuzumab deruxtecan in participants with HER2-mutated metastatic non-small cell lung cancer. The registry reports 152 participants enrolled and two arms.
| Feature | DESTINY-Lung02 |
|---|---|
| Trial name | DESTINY-Lung02 |
| Phase | Phase 2 |
| Condition | Non-Small Cell Lung Cancer |
| Population | Participants with HER2-mutated metastatic non-small cell lung cancer |
| Intervention | Trastuzumab deruxtecan |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Primary purpose | Treatment |
| Enrollment | 152 |
| Trial status | COMPLETED |
| Lead sponsor | Daiichi Sankyo |
| Sponsor type | INDUSTRY |
| ClinicalTrials.gov | NCT04644237 |
2. Clinical Question
The registry describes a phase 2 randomized trial of intravenous trastuzumab deruxtecan in participants with HER2-mutated metastatic non-small cell lung cancer. The registered primary question is centered on the confirmed objective response rate assessed by blinded independent central review.
Population
Participants with HER2-mutated metastatic non-small cell lung cancer.
Intervention
Trastuzumab deruxtecan administered by intravenous administration.
Comparator structure
The registry describes two randomized trastuzumab deruxtecan arms: 5.4 mg/kg and 6.4 mg/kg are identified in the reported serious-adverse-event denominators.
Primary question
What proportion of participants achieve a confirmed complete or partial response according to blinded independent central review using RECIST version 1.1?
3. Trial Design
Trastuzumab deruxtecan
- Trastuzumab deruxtecan
- Registry safety denominator: 101 participants at risk
- Serious adverse events: 42 affected
Trastuzumab deruxtecan
- Trastuzumab deruxtecan
- Registry safety denominator: 50 participants at risk
- Serious adverse events: 26 affected
4. Trial Timeline
Trial start
The ClinicalTrials.gov record lists 2021-03-19 as the trial start date.
Primary completion
The ClinicalTrials.gov record lists 2022-12-23 as the primary completion date.
Current registry status in the ClinicalTrials.gov record
The trial status is reported as COMPLETED.
5. Primary Endpoint
| Endpoint | Registry definition | Time frame | Type |
|---|---|---|---|
| Confirmed objective response rate | 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. Confirmed ORR is defined as the proportion of participants with complete response (CR) or partial response (PR), assessed by BICR based on RECIST version 1.1. CR is defined as disappearance of all target lesions and PR as at least a 30% decrease in the sum of diameters of target lesions. | 9 months after the last participant is randomized to data cut off, up to approximately 21 months | Binary |
6. Results
The ClinicalTrials.gov record indicates that results are posted and that 13 outcome measures are posted. However, no formal statistical analyses were posted. Consequently, there are no formal statistical comparison estimates, confidence intervals, or p-values for the primary endpoint in the ClinicalTrials.gov record.
Primary endpoint: confirmed ORR
Results are posted in the registry, but the ClinicalTrials.gov record contains no analysis estimate, confidence interval, or p-value.
The endpoint is binary and is assessed by blinded independent central review using RECIST version 1.1.
A confirmed objective response rate is a proportion: each participant is classified according to whether the prespecified response criterion is met. The ClinicalTrials.gov record identifies the endpoint and its assessment framework, but they do not provide the observed proportion in either arm.
For that reason, no numerical treatment effect should be inferred from the fact that results are posted. A posted outcome measure is not equivalent to a reported formal statistical comparison.
A confidence interval would quantify uncertainty around an estimated response proportion or treatment contrast. Without the numerical estimate and its interval, the precision of the observed response cannot be evaluated from the registry-reported statistical-analysis field.
A p-value, if formally specified for a comparison, would address evidence against a prespecified null hypothesis. It would not itself measure the magnitude or clinical importance of a response-rate difference.
What would normally be reported for a binary response endpoint?
A complete statistical report would ordinarily provide the response count and denominator for each arm, the corresponding response proportion, an appropriate confidence interval, and—if a between-arm hypothesis test is prespecified—the treatment comparison with its confidence interval and p-value.
Possible approaches for a randomized two-arm binary endpoint include exact or score-based confidence intervals for each response proportion and an appropriate two-group comparison of proportions. The exact method depends on the prespecified statistical analysis plan, which is not reported here. The registry data therefore support explanation of the statistical framework, but not selection of a specific formal test as the trial's actual analysis.
7. Understanding Confirmed Objective Response
The primary endpoint is not simply whether a tumor became smaller at one assessment. It is a confirmed objective response, meaning the registry defines the response category in terms of complete response or partial response and specifies blinded independent central review using RECIST version 1.1.
Complete response
The registry definition describes CR as disappearance of all target lesions.
Partial response
The registry definition describes PR as at least a 30% decrease in the sum of diameters of target lesions, with the definition text reported in the ClinicalTrials.gov record ending at that point.
Blinded review
Assessment was specified to use blinded independent central review, reducing the role of knowledge of treatment assignment in radiologic assessment.
Binary analysis
The registered primary endpoint is classified as binary, so each participant contributes to a response/nonresponse outcome under the prespecified assessment rules.
8. Statistical Methodology
Binary response analysis
Unlike overall survival or progression-free survival, objective response rate is not intrinsically a time-to-event endpoint. The primary analysis therefore begins with a binary classification: response or no response according to the prespecified RECIST-based assessment.
The response proportion estimates the probability of a confirmed CR or PR within the defined analysis population and assessment framework.
Confidence intervals for a response proportion
A response proportion should be accompanied by a confidence interval because the observed proportion is estimated from a finite sample. For example, if x of n participants respond, the point estimate is x/n. Several interval procedures are possible, including exact binomial and score-based methods.
The appropriate interval method should be taken from the trial's prespecified statistical analysis plan when available. The ClinicalTrials.gov record does not identify the confidence-interval procedure used for DESTINY-Lung02.
Comparing two randomized arms
Because the trial is randomized and has two parallel arms, a formal comparison can be framed as a difference, ratio, or odds ratio between response probabilities. The choice of effect measure and hypothesis test should be prespecified rather than selected after seeing the observed results.
These are different estimands. A statistical analysis should identify which one was prespecified rather than treating them as interchangeable.
Independent central review
The use of blinded independent central review is particularly relevant for radiologic endpoints. It creates a standardized assessment process intended to reduce differential interpretation of imaging according to treatment assignment. The statistical analysis remains dependent on how participants are defined as evaluable, how missing assessments are handled, and how confirmation requirements are operationalized.
Randomization
Randomization is the foundation for comparing the treatment groups. In a randomized parallel trial, the treatment assignment process is intended to balance measured and unmeasured baseline factors in expectation. The ClinicalTrials.gov record identifies the allocation as randomized but does not provide a randomization ratio or stratification factors.
Blinding
The ClinicalTrials.gov record describes the study as double masked. Blinding can reduce differential behavior, assessment, and reporting related to knowledge of treatment assignment. For a response endpoint based on radiologic review, the registry additionally specifies blinded independent central review.
9. Statistical Methods Explained
Why is ORR treated as a binary endpoint?
Each participant can be classified according to whether the prespecified confirmed CR or PR criterion is met. That creates a binary outcome for the primary endpoint. The analysis can then estimate the response probability and compare response probabilities between randomized groups if a formal comparison is specified.
Why is blinded independent central review important?
Radiologic response assessments involve interpretation of imaging. If the reviewer knows treatment assignment, that knowledge can potentially influence classification. Blinded independent central review separates the radiologic assessment from treatment knowledge and provides a standardized basis for the response endpoint.
Why does a confidence interval matter for ORR?
A point estimate alone does not show how precisely the underlying response probability has been estimated. A confidence interval describes statistical uncertainty around the estimate under the chosen interval procedure. Wider intervals generally indicate less precision than narrower intervals, although the interval must be interpreted within the design and analysis framework.
What would a response-rate difference mean?
A risk difference compares the estimated response probabilities directly. For example, a positive difference would indicate a higher estimated response probability in the numerator-defined treatment group. It would not automatically establish that the difference is clinically important; that interpretation depends on the prespecified clinical context and the uncertainty around the estimate.
Why is a p-value not the same as effect size?
A p-value evaluates evidence relative to a null hypothesis under the statistical model and testing procedure. It is affected by sample size and does not describe the magnitude of the treatment effect. A complete interpretation should therefore consider the estimated response proportions, the effect measure, its confidence interval, and the clinical meaning of the endpoint.
Why does confirmation matter?
The word "confirmed" means that the response classification is subject to the confirmation rules specified by the trial. Confirmation can reduce the chance that a transient or uncertain radiologic change is counted as an objective response. The exact operational confirmation schedule is not fully reported in the registry excerpt provided for this analysis.
10. Analysis Time Frame
The registered primary endpoint has a specific time frame: 9 months after the last participant is randomized to data cut off, up to approximately 21 months.
Starting point
9 months after the last participant is randomized.
Data cutoff
The primary endpoint time frame extends to data cutoff, up to approximately 21 months.
Why the cutoff matters
Response estimates are tied to the prespecified assessment period. Changing the cutoff can change which assessments are available for analysis.
Interpretive caution
A response rate from one cutoff should not be silently combined with a response rate from another analysis time point.
11. Safety Results
The ClinicalTrials.gov record reports serious adverse events by arm. The affected and at-risk counts are presented below exactly as provided.
| Arm | Serious adverse events affected | At risk | Registry-reported measure |
|---|---|---|---|
| Trastuzumab deruxtecan 5.4 mg/kg | 42 | 101 | 42/101 |
| Trastuzumab deruxtecan 6.4 mg/kg | 26 | 50 | 26/50 |
The raw serious-adverse-event counts show that 42 participants in the 5.4 mg/kg arm and 26 participants in the 6.4 mg/kg arm were reported as affected among the respective registry denominators of 101 and 50.
These counts should not be converted into a between-arm statistical comparison without knowing the prespecified safety analysis population, event definitions, exposure time, handling of multiple events per participant, and statistical analysis plan.
The denominators also differ, so the raw affected counts alone cannot be interpreted as evidence of a difference in safety frequency.
12. What the Available Results Do and Do Not Establish
| Question | What the ClinicalTrials.gov record establishes | What they do not establish |
|---|---|---|
| Was the trial randomized? | Yes. The allocation is reported as randomized. | The ClinicalTrials.gov record does not give the randomization ratio or stratification factors. |
| Was the study blinded? | Yes. Masking is reported as double. | The ClinicalTrials.gov record does not specify the identities of all blinded parties. |
| What was the primary endpoint? | Confirmed ORR by BICR using RECIST version 1.1. | The ClinicalTrials.gov record does not provide a numerical ORR estimate. |
| Were results posted? | Yes. Results Posted is reported as Yes and 13 outcome measures are posted. | The registry-reported statistical-analysis field contains no formal statistical analyses. |
| Was a formal treatment-effect estimate reported? | No estimate is present in the posted results. | A numerical difference, ratio, odds ratio, confidence interval, or p-value cannot be reported from the ClinicalTrials.gov record. |
| What safety information is available? | Serious adverse-event counts are posted on ClinicalTrials.gov for both dose groups. | The ClinicalTrials.gov record does not provide a complete safety table or formal safety comparison. |
13. Limitations
- No formal statistical analyses reported: although the registry indicates that results are posted, no formal statistical analyses were posted. Numerical efficacy estimates, confidence intervals, and p-values therefore cannot be reconstructed from the ClinicalTrials.gov record.
- Incomplete endpoint definition excerpt: the registry-reported definition of partial response ends after "at least a 30% decrease in the sum of diameters of," so this page does not add the missing text from another source.
- Unknown randomization ratio: the trial is described as randomized with two arms, but the ClinicalTrials.gov record does not state the allocation ratio.
- Unknown stratification factors: the ClinicalTrials.gov record does not identify stratification variables or whether stratified analyses were prespecified.
- Unknown analysis population: the ClinicalTrials.gov record identifies the primary endpoint as binary but does not specify the complete efficacy analysis population or rules for evaluability.
- Missing-data methodology not reported: the registry excerpt does not identify how missing imaging assessments, withdrawals, or unevaluable participants were handled for the primary endpoint.
- No multiplicity information: the ClinicalTrials.gov record does not describe alpha allocation, hierarchical testing, multiplicity adjustment, or the relationship between the primary endpoint and other posted outcomes.
- No interim-analysis information: the ClinicalTrials.gov record does not describe interim statistical monitoring or stopping boundaries.
- No Bayesian methodology reported: the ClinicalTrials.gov record does not identify a Bayesian analysis, prior distribution, posterior probability, or Bayesian decision rule.
- Safety denominator discrepancy: the registry-reported serious-adverse-event denominators are 101 and 50, while total enrollment is 152. The data provided do not explain the one-participant difference between the sum of those denominators and total enrollment.
- External validity: the ClinicalTrials.gov record identifies a specific population with HER2-mutated metastatic non-small cell lung cancer. The ClinicalTrials.gov record does not contain enough baseline or eligibility detail to characterize generalizability beyond that description.
14. Why This Trial Matters Statistically
DESTINY-Lung02 is useful as a statistical teaching case because it illustrates a different endpoint structure from trials dominated by overall survival or progression-free survival. Its registered primary endpoint is a binary confirmed objective response rate, assessed by blinded independent central review.
| Concept | How it appears in DESTINY-Lung02 |
|---|---|
| Randomization | The trial is randomized. |
| Parallel design | The design model is reported as parallel with two arms. |
| Blinding | The registry reports double masking. |
| Binary endpoint | The primary endpoint is classified as binary. |
| Objective response rate | The primary endpoint is confirmed ORR. |
| Independent review | ORR is assessed by blinded independent central review. |
| RECIST 1.1 | Response classification is based on RECIST version 1.1. |
| Time frame | The registered endpoint is assessed from 9 months after the last participant is randomized to data cutoff, up to approximately 21 months. |
| Safety analysis | Serious adverse-event counts are reported separately for the 5.4 mg/kg and 6.4 mg/kg arms. |
| Registry interpretation | Results are posted, but the ClinicalTrials.gov record contains no formal statistical comparison. |
15. A Deeper Look at Binary Endpoint Precision
For a binary endpoint, sample size has a direct effect on statistical precision. Suppose an arm contains n evaluable participants and x meet the response criterion. The observed response rate is x/n. The uncertainty around that estimate depends on both the observed proportion and the number of observations.
The formula describes the statistical structure of the endpoint; it does not supply an observed DESTINY-Lung02 result. The ClinicalTrials.gov record does not provide the responder counts or numerical ORR estimates needed to calculate them.
This distinction is important. It would be possible to construct a hypothetical response-rate example, but doing so could be mistaken for a reported trial result. This page therefore keeps the mathematical explanation separate from the trial's missing numerical efficacy results.
16. Why Blinding and Randomization Matter Together
Randomization and blinding address different sources of bias. Randomization concerns how participants are assigned to treatment groups. Blinding concerns whether knowledge of that assignment is available to participants, investigators, assessors, or other trial personnel, depending on the protocol.
Randomization
Creates the basis for a randomized comparison by assigning participants to treatment groups according to the trial's allocation process.
Blinding
Can reduce the influence of treatment knowledge on behavior, assessment, and reporting.
Central review
The primary endpoint specifically uses blinded independent central review, adding an assessment layer for the radiologic response determination.
Combined interpretation
These design features address different parts of the causal and measurement process and should not be treated as interchangeable statistical safeguards.
17. Primary Analysis: What a Complete Statistical Report Would Contain
For an educational analysis of a randomized binary response endpoint, a complete report would ideally identify the analysis population, response counts, response proportions, effect measure, confidence interval, hypothesis test, and prespecified significance framework.
| Component | Purpose | DESTINY-Lung02 information reported |
|---|---|---|
| Analysis population | Defines who contributes to the primary endpoint. | Not reported in the provided statistical-analysis data. |
| Responder count | Numerator for the ORR estimate. | Not reported. |
| Evaluable denominator | Defines the population used for the response proportion. | Not posted on ClinicalTrials.gov for the primary endpoint. |
| ORR | Describes the observed confirmed response proportion. | Not numerically reported. |
| Effect measure | Quantifies the difference or relative association between arms. | Not reported. |
| Confidence interval | Describes uncertainty around the estimate. | Not reported. |
| P-value | Evaluates evidence under a specified null hypothesis and test. | Not reported. |
| Multiplicity plan | Controls interpretation when multiple hypotheses are tested. | Not reported. |
The absence of these values in the registry-reported statistical-analysis object is not evidence that the investigators did not perform those analyses. It means only that those formal analysis results were not included in the ClinicalTrials.gov record.
18. Safety Interpretation
Safety results require a different statistical perspective from the primary response endpoint. A serious adverse event is an event classification, whereas ORR is a participant-level efficacy classification. Safety summaries can also involve repeated events, varying exposure duration, treatment discontinuation, and multiple event categories.
The reported serious-adverse-event counts of 42/101 and 26/50 should be read as the registry's affected/at-risk summaries. They do not by themselves establish a statistically significant difference between doses.
A formal comparison would require a defined safety analysis population and a prespecified approach to event counting. For example, a participant-level analysis of whether at least one serious adverse event occurred is different from an analysis of the total number of serious adverse events.
The ClinicalTrials.gov record does not specify which of these possible frameworks was used, so no additional safety effect measure is inferred here.
19. Clinical Interpretation vs Statistical Interpretation
Statistical interpretation
The primary endpoint is a binary confirmed response outcome assessed by blinded independent central review. The ClinicalTrials.gov record does not contain the formal numerical statistical analysis of that endpoint.
Clinical interpretation
The trial evaluates trastuzumab deruxtecan in participants with HER2-mutated metastatic non-small cell lung cancer. The available data establish the trial's design and endpoint framework but do not provide enough numerical efficacy information here to quantify the treatment effect.
20. What Cannot Be Concluded From the ClinicalTrials.gov record
- A numerical objective response rate cannot be reported because the ClinicalTrials.gov record does not provide the response count or response proportion.
- A numerical difference between the two treatment arms cannot be reported because no arm-level primary efficacy estimates are reported.
- A hazard ratio cannot be reported because the primary endpoint is binary and no time-to-event statistical analysis is reported.
- A confidence interval for the primary endpoint cannot be reported because no primary endpoint estimate or statistical-analysis object is reported.
- A p-value for the primary endpoint cannot be reported because no formal statistical test result is reported.
- No conclusion about which dose produced a higher response rate should be inferred from the serious-adverse-event counts.
- No conclusion about dose-related efficacy can be made from the ClinicalTrials.gov record because the primary efficacy results are not numerically reported in the provided statistical-analysis field.
21. Related Tutorials
Learn more about the methods used in this trial:
22. Related Statistical Calculators
23. Sources
- ClinicalTrials.gov: NCT04644237 — DESTINY-Lung02.
- Linked publication record: PubMed PMID 41689406.
- Linked publication record: PubMed PMID 40749900.
- Linked publication record: PubMed PMID 37694347.
Continue through the Clinical Biostats statistical pathway
Explore the underlying clinical-trial and binary-endpoint methods used to understand randomized response-rate analyses.
24. Record Summary
DESTINY-Lung02 is a completed randomized, double-masked, parallel phase 2 trial with 152 participants enrolled and two arms evaluating trastuzumab deruxtecan in participants with HER2-mutated metastatic non-small cell lung cancer. Its registered primary endpoint is confirmed objective response rate assessed by blinded independent central review using RECIST version 1.1, with the registered time frame beginning 9 months after the last participant is randomized and extending to data cutoff, up to approximately 21 months.
The ClinicalTrials.gov record indicates that results are posted, but it does not supply a formal statistical-analysis object for the primary endpoint. Accordingly, the most defensible statistical interpretation is methodological rather than numerical: the primary endpoint is a binary response measure requiring an explicitly defined analysis population, response count, denominator, effect measure, confidence interval, and hypothesis-testing framework for a complete quantitative comparison. None of those numerical primary efficacy results are reported here, so they have not been reconstructed or imported from another source.
The ClinicalTrials.gov record consists of serious-adverse-event counts of 42/101 for trastuzumab deruxtecan 5.4 mg/kg and 26/50 for trastuzumab deruxtecan 6.4 mg/kg. These figures should be interpreted as registry-reported affected/at-risk summaries rather than as a formal between-dose statistical comparison.