This page separates reported trial information from statistical interpretation. The ClinicalTrials.gov record identifies results as posted, but contain no formal statistical analyses in the statistical-analysis field.
1. Trial at a Glance
DESTINY-Lung01 was a phase 2, non-randomized, parallel-design clinical trial evaluating trastuzumab deruxtecan in participants with HER2-expressing or -mutated non-small cell lung cancer. The registered primary endpoint was the percentage of participants with objective response rate based on independent central review following treatment with DS-8201a.
| Feature | DESTINY-Lung01 |
|---|---|
| Trial name | DESTINY-Lung01 |
| ClinicalTrials.gov identifier | NCT03505710 |
| Brief title | DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing or -Mutated Non-Small Cell Lung Cancer |
| Therapeutic area | Oncology |
| Phase | 2 |
| Status | TERMINATED |
| Enrollment | 181.0 |
| Allocation | NON_RANDOMIZED |
| Design model | PARALLEL |
| Masking | NONE |
| Primary purpose | TREATMENT |
| Intervention | Trastuzumab deruxtecan (drug) |
| Registered primary endpoints | 1 |
| Primary endpoint type | Binary |
| Results posted | Yes |
| Outcome measures posted | 6 |
2. Clinical Question
The central statistical question was descriptive and response-focused: among participants with HER2-expressing or -mutated non-small cell lung cancer treated with DS-8201a, what percentage achieved a confirmed objective response according to independent central review?
Population
Participants with HER2-expressing or -mutated non-small cell lung cancer.
Intervention
Trastuzumab deruxtecan (DS-8201a).
Comparator
The ClinicalTrials.gov record does not identify a randomized comparator treatment. The allocation is recorded as NON_RANDOMIZED.
Primary question
What percentage of participants achieved a confirmed complete or partial response based on independent central review using RECIST version 1.1?
3. Trial Design
Study population and cohorts
The ClinicalTrials.gov record identifies three cohorts within the study: Cohort 1, HER2 Overexpressing; Cohort 1a, HER2 Overexpressing; and Cohort 2, HER2 Mutated. The registry profile records 3 arms and an overall enrollment of 181.0 participants.
| Cohort | Description | Serious adverse events affected / at risk |
|---|---|---|
| Cohort 1 | HER2 Overexpressing | 28/49 |
| Cohort 1a | HER2 Overexpressing | 18/41 |
| Cohort 2 | HER2 Mutated | 40/91 |
4. Endpoints
| Endpoint | Registry definition / assessment | Time frame |
|---|---|---|
| Objective Response Rate (ORR) | The percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by independent central review (ICR) committee based on RECIST version 1.1. | From screening, up to 36 months (data cut-off) |
What the endpoint measures
Objective response rate is a binary participant-level outcome: a participant either meets the prespecified definition of confirmed CR or PR or does not. The endpoint therefore differs fundamentally from a time-to-event endpoint such as overall survival or progression-free survival.
The formula is shown here as a statistical explanation of the registered binary endpoint. The ClinicalTrials.gov record does not provide the numerator, denominator for the efficacy analysis, or resulting ORR estimate.
The use of independent central review is statistically important because response classification is based on an independent assessment rather than simply relying on an investigator's local assessment. The registry definition specifies RECIST version 1.1 as the response-assessment framework.
5. Results
Primary endpoint: Objective Response Rate
The registered primary endpoint is the percentage of participants with objective response rate based on independent central review following treatment with DS-8201a. The endpoint was assessed from screening up to 36 months, at the data cut-off.
Reported statistical estimate
The ClinicalTrials.gov record contains no formal statistical analysis for the primary endpoint.
What the estimate would mean: an ORR estimate would represent the proportion of participants meeting the confirmed CR or PR definition under independent central review. It would be an absolute response proportion, not a hazard ratio or relative treatment effect.
What it would not mean: in this non-randomized design, an ORR estimate would not by itself demonstrate that trastuzumab deruxtecan causes more responses than another treatment. Without a randomized comparator, there is no internally randomized treatment contrast from which to estimate a comparative treatment effect.
Precision: a confidence interval around ORR would quantify statistical uncertainty in the estimated response proportion. The ClinicalTrials.gov record contains no such interval, so precision cannot be quantified from the provided record.
P-value: a p-value would address a specified null hypothesis, but it would not measure the magnitude of the response rate or the clinical importance of the observed response proportion. No p-value is reported.
Assessment framework: independent central review and RECIST version 1.1 define how the binary response outcome is classified. The endpoint therefore depends not only on treatment exposure but also on the prespecified response-assessment process.
What analysis would normally be used?
For a binary ORR endpoint, the primary descriptive analysis would normally report the number and percentage of participants achieving confirmed CR or PR, together with an appropriate confidence interval for the response proportion. Depending on the prespecified statistical plan, an exact binomial interval or another binomial proportion interval could be used. A hypothesis test would require a clearly defined null response rate or comparator.
The correct statistical conclusion from the ClinicalTrials.gov record is limited to the endpoint definition and the study design.
6. Safety Results
the ClinicalTrials.gov record reports serious adverse events by cohort as affected participants divided by participants at risk. These are the only safety results provided in the trial data.
| Cohort | Serious adverse events | Interpretation of reported quantity |
|---|---|---|
| Cohort 1: HER2 Overexpressing | 28/49 | 28 affected participants among 49 at risk |
| Cohort 1a: HER2 Overexpressing | 18/41 | 18 affected participants among 41 at risk |
| Cohort 2: HER2 Mutated | 40/91 | 40 affected participants among 91 at risk |
These counts are cohort-level safety summaries rather than randomized comparisons. The ClinicalTrials.gov record does not provide confidence intervals, hypothesis tests, exposure-adjusted rates, event dates, severity distributions, or formal comparisons between the cohorts.
The denominators are important: a count such as 28 must be interpreted in relation to the 49 participants at risk in that cohort. It should not be treated as a percentage unless a percentage is explicitly calculated and labeled as a derived quantity. This page retains the registry's reported affected/at-risk format.
7. Statistical Methodology
Binary endpoint analysis
The registered primary endpoint is binary because each participant's best overall response is classified into categories and the primary outcome is whether the participant achieved a confirmed CR or PR. The natural statistical summary is therefore a proportion.
The observed ORR is the mean of these binary indicators in the prespecified analysis population.
Independent central review
The registered endpoint specifies assessment by an independent central review committee. Central review is intended to provide a consistent assessment framework across participants and reduces reliance on individual investigator assessments when classifying radiologic response.
RECIST version 1.1
The registry specifies RECIST version 1.1 as the framework used by the independent central review committee. The registry-reported endpoint definition states that a confirmed complete response requires disappearance of all target lesions and that a partial response requires at least a 30% decrease in the sum of diameters of target lesions.
Why a confidence interval belongs with ORR
An observed response percentage is a sample estimate. Its uncertainty depends on the number of participants and the number of observed responses. A confidence interval therefore provides information that the point estimate alone cannot: it describes the statistical precision of the estimated response proportion under the chosen inferential framework.
Why randomization matters
This study is recorded as NON_RANDOMIZED. That design feature changes what can be inferred from the primary endpoint. In a randomized comparative trial, differences between treatment groups can be interpreted using the randomization mechanism. In a non-randomized response study, the response proportion primarily describes the observed study population and cannot, by itself, separate treatment effects from differences in patient characteristics, disease characteristics, eligibility, or other sources of confounding.
8. Statistical Methods Explained
Why is ORR treated as a binary endpoint?
Because the registered endpoint asks whether a participant achieved a confirmed CR or PR, each participant can be classified according to whether the response criterion was met. The aggregate result is consequently a proportion rather than a time-to-event estimate.
Why use independent central review?
The registry specifically identifies independent central review as the assessment method. This creates a common assessment process for determining response and can reduce variability that might arise if response were based only on individual investigator assessments.
Why does RECIST version 1.1 matter?
A response percentage is only meaningful when the response definition is specified. RECIST version 1.1 supplies the framework used for classifying tumor response, while the registry's endpoint definition specifies confirmed CR or PR as the response criterion.
What would a confidence interval tell us about ORR?
A confidence interval would quantify uncertainty around the estimated response proportion. A narrow interval would indicate greater statistical precision than a wide interval, all else being equal. The ClinicalTrials.gov record does not provide an ORR confidence interval.
Why can't an ORR from this study automatically establish comparative efficacy?
The allocation is NON_RANDOMIZED and no randomized comparator is identified in the ClinicalTrials.gov record. An observed response proportion can therefore describe the study cohort but cannot by itself establish how the intervention would perform relative to another treatment.
Why is the analysis population important?
The denominator determines the meaning of a response proportion. For example, an ORR calculated among all enrolled participants is conceptually different from an ORR calculated among participants who received treatment or among participants evaluable for response. The ClinicalTrials.gov record does not identify the denominator used for the posted efficacy outcome, so this page does not assume one.
9. What the Trial Design Does — and Does Not — Permit
What can be described
The study enrolled 181.0 participants, used a non-randomized parallel design, evaluated trastuzumab deruxtecan, and registered ORR based on independent central review as its primary endpoint.
What requires caution
A response proportion from a non-randomized study should not be interpreted as a randomized treatment effect or as evidence that the intervention is superior to an unspecified comparator.
What the registry reports
Results are posted, with 6 outcome measures posted in the ClinicalTrials.gov record.
What the ClinicalTrials.gov record omit
The statistical-analysis field contains no analyses. No formal ORR estimate, confidence interval, p-value, or comparative treatment estimate is reported.
10. Important Limitations and Interpretation Issues
- Non-randomized design: the trial is recorded as NON_RANDOMIZED, so the primary response endpoint does not provide a randomized treatment comparison.
- Incomplete statistical results in the ClinicalTrials.gov record: results are identified as posted, but the registry-reported statistical-analysis field is empty. The numerical efficacy result cannot therefore be reconstructed from the ClinicalTrials.gov record from the registry record aloneset.
- Unknown efficacy denominator: the ClinicalTrials.gov record does not state the analysis population or denominator used for the posted ORR result.
- No confidence interval reported in the ClinicalTrials.gov record: precision around the primary response estimate cannot be assessed from the provided record.
- No p-value reported: there is no registry-reported formal hypothesis test for the primary endpoint.
- Three-arm structure: the ClinicalTrials.gov record records 3 arms, but the ClinicalTrials.gov record does not provide a complete treatment description or sample size for each arm beyond the cohort-level serious-adverse-event denominators.
- Safety interpretation: serious-adverse-event counts are reported by cohort, but the ClinicalTrials.gov record does not provide formal between-cohort statistical comparisons.
- External validity: the ClinicalTrials.gov record identifies the condition and HER2-expressing or -mutated population but do not provide a baseline-characteristics table sufficient for a detailed assessment of generalizability.
11. Why This Trial Matters Statistically
DESTINY-Lung01 is a useful teaching example because it illustrates a different statistical problem from a randomized survival trial. Its primary endpoint is a binary response outcome, the design is non-randomized, and the response classification uses independent central review under RECIST version 1.1.
| Concept | How it appears in DESTINY-Lung01 |
|---|---|
| Binary endpoint | The registered primary endpoint is objective response rate. |
| Response proportion | ORR summarizes the percentage achieving confirmed CR or PR. |
| Independent central review | Response is assessed by an independent central review committee. |
| RECIST version 1.1 | The registry identifies RECIST version 1.1 as the response-assessment framework. |
| Non-randomized design | The allocation is recorded as NON_RANDOMIZED. |
| Parallel design | The design model is recorded as PARALLEL. |
| Three-arm structure | the ClinicalTrials.gov record records 3 arms. |
| Confidence intervals | Would normally accompany an estimated response proportion to describe statistical precision; none is reported in the provided analysis data. |
| Hypothesis testing | Would require a prespecified null response rate or comparator; no such formal analysis is reported. |
| Safety denominators | Serious adverse events are reported as affected participants divided by participants at risk for each identified cohort. |
12. Related Tutorials
Learn more about the methods used in this trial:
13. Related Statistical Calculators
14. Sources
- ClinicalTrials.gov: NCT03505710 — DESTINY-Lung01. Trial design, endpoint definitions, study dates, enrollment, intervention, status, and safety information used on this page.
- PubMed record: PMID 39012221.
- PubMed record: PMID 38547891.
- PubMed record: PMID 34534430.
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15. Record Summary
DESTINY-Lung01 is a phase 2, non-randomized, parallel clinical trial with 181.0 participants and 3 recorded arms, evaluating trastuzumab deruxtecan in HER2-expressing or -mutated non-small cell lung cancer. Its registered primary endpoint is the percentage of participants with confirmed objective response based on independent central review using RECIST version 1.1, assessed from screening up to 36 months at the data cut-off. The ClinicalTrials.gov record reports that results are posted, but it does not provide formal statistical analyses or the numerical ORR result. The appropriate statistical interpretation is therefore to focus on the binary endpoint, its response-assessment framework, the implications of a non-randomized design, and the distinction between descriptive response evidence and randomized comparative efficacy.