A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer (NCT04564027), a non-randomized phase 2 study. The primary outcome is Cohort A (aST): Objective Response Rate (ORR)..

2. Clinical Question

3. Trial Design

PLANETTE is described in the registry as a modular, multicentre, open-label phase 2a study investigating DNA-damage response agents or combinations in advanced cancer with molecular alterations. The registered intervention in this record is ceralasertib. The trial is marked completed, with enrollment of 54. Its recorded start date is 2020-12-01 and primary completion date is 2025-02-18. The sponsor is AstraZeneca.

The design fields identify the study as non-randomized and single group, with no masking. The listed treatment cohorts are Cohort A, described as ATM-altered aST, and Cohort B, described as ATM-altered mCRPC. Both cohort descriptions specify oral ceralasertib monotherapy. The registry lists 240 mg and 160 mg groups within each cohort for safety reporting. This should not be mistaken for a randomized dose comparison: allocation was non-randomized, and the registry specifically says participants starting at 240 mg were not included in efficacy analyses for either cohort.

The primary outcome listed is objective response rate in Cohort A. Secondary outcomes include duration of radiological response, progression-free survival and percentage change in tumour size for Cohort A; percentage change in tumour size for Cohort B; and serious and non-serious adverse events in both cohorts. These are outcome descriptions, not results. The registry lists seven outcome measures and no analyses. It does not report the protocol’s statistical analysis plan, sample-size justification, interim analysis arrangements or how treatment assignment to dose groups occurred. Those details should not be inferred from the design label or from the existence of different dose groups.

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: The screening comprised of 2 parts, Part1 and Part 2, which applied for both Cohort A and Cohort B. Participants meeting the inclusion criteria were enrolled in the study. All the assessments were performed as per the schedule of the assessments.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable for response set included all participants who were Molecularly Eligible Centrally Confirmed evaluable for response set with measurable disease at baseline and who received at least 1 dose of study intervention.

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: Safety analysis set consists of all participants who received at least 1 dose of study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Cohort A (aST): Objective Response Rate (ORR)., measured over 2 years 4 months.

The primary endpoint is the percentage of Cohort A participants who have at least one confirmed complete or partial response before evidence of progression, assessed using RECIST 1.1. A complete response means disappearance of all target and non-target lesions with no new lesions. A partial response requires at least a 30% decrease from baseline in the sum of target-lesion diameters and no new non-target lesion. The response must be confirmed at least 4 weeks later.

Objective response rate is a binary-outcome summary: each person in the response-evaluable population either meets the response definition or does not. Expressing the result as a percentage gives a measure of how commonly the specified tumour response was observed in that population. It does not describe how long a response lasted; duration of radiological response is listed separately as a secondary outcome. Nor does ORR by itself capture every aspect of tumour change or disease course.

The record specifies an 80% confidence interval and a timeframe of 2 years 4 months, but reports no response percentage or interval limits. It defines the response-evaluable population as participants centrally confirmed to be molecularly eligible, with measurable disease at baseline, who received at least one dose. The record also states that participants starting at 240 mg were excluded from efficacy analyses. Consequently, the primary endpoint is not described as an estimate for every enrolled participant.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record names an objective response rate and an 80% confidence interval, but does not report the numerical response estimate or the interval limits. It also lists no analyses. The statistical concepts below explain how these methods are generally used; they are not a claim that any unreported procedure was used in this trial.

What does an objective response rate represent?

For a binary endpoint, each participant is classified according to whether the prespecified event occurred. For this endpoint, the event is a complete or partial response meeting RECIST 1.1 criteria and confirmed at least 4 weeks later, before evidence of progression. The response rate is the proportion of the defined analysis population meeting that event definition, expressed as a percentage. The registry identifies the analysis population as centrally confirmed, molecularly eligible participants with measurable disease at baseline who received at least one dose.

That definition matters because the percentage depends on who is included and what counts as a response. The record says participants starting at 240 mg were excluded from efficacy analyses in both cohorts. It does not report the number included in the primary analysis, the response count, or how participants without an assessable response were handled. A reader therefore cannot reconstruct the response percentage from the registry entry.

What does a confidence interval add?

General explanation: a confidence interval gives a range of values compatible with the observed data under the statistical method and its assumptions. It conveys uncertainty in an estimate, rather than guaranteeing that the true value lies in a particular interval. The registry specifies an 80% confidence interval for the primary endpoint, but supplies neither its endpoints nor the method used to calculate it. The interval level alone does not reveal the estimate’s precision.

Why do the design features matter?

General explanation: randomization can make treatment groups more comparable, on average, with respect to both measured and unmeasured factors. A non-randomized single-group design does not create that kind of concurrent control comparison. Open-label status means the record describes no masking; it does not establish which assessment procedures were used to reduce potential assessment bias. For a response endpoint based on lesion assessment, the registry’s use of RECIST 1.1 defines the response criteria, but details such as independent review are not reported in the registry record.

The two dose levels should not be treated as randomized alternatives. The registry describes a sponsor dose reduction after a toxicity observation and excludes the 240 mg starters from efficacy analyses. It does not report the dose-assignment process, timing by participant, or any adjusted comparison. General explanation: if dose groups arise at different stages or through different eligibility decisions, their characteristics and observation periods may differ. A numerical contrast would not, by itself, separate dose effects from those differences.

What can be said about planning calculations?

The record describes a sample-size planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; it says the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration is described in terms of total events, and for other outcomes in terms of participants per arm. No numerical illustration results or observed effect are reported in the registry record. These are planning assumptions, not observed power, and do not establish the trial’s original design justification. The registry does not report that justification.

General explanation: a planning calculation estimates the sample size needed to detect a specified effect under chosen assumptions. It is not a measure of the probability that a completed study has demonstrated an effect, and assumptions may not match the realized study design. The described equal-allocation, two-arm illustration should not be confused with this study’s recorded single-group, non-randomized design.

What statistical details remain unclear?

The record does not report the confidence-interval calculation method, a hypothesis-testing procedure for the primary endpoint, covariate adjustment, handling of multiple outcomes, missing-data rules, sensitivity analyses, or the treatment of participants with no post-baseline assessment. It also lists no analysis results. These omissions limit the ability to assess assumptions and reproducibility. General explanation: such details can affect which observations contribute to an estimate and how uncertainty is quantified. They cannot be reconstructed from the endpoint definition alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort A (aST): 160 mg of Ceralasertib")
n      <- c(28)
events <- c(2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort A (aST): 160 mg of Ceralasertib  28  2  7.1  0.9  23.5  2.0  22.6  2.2  22.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, including the Cohort A primary objective response rate and secondary measures of response duration, progression-free survival, tumour-size change and adverse events. It lists no analyses. The registry record does not report a multiplicity strategy, such as a hierarchy of outcome tests or an adjustment for examining several endpoints. Without an analysis plan and reported tests, it is not possible to determine how any multiplicity was handled.

The registry record does not report how missing endpoint data were handled, how participants without a response assessment were classified, or whether any sensitivity analyses were planned. It defines the response-evaluable population as participants with central confirmation of molecular eligibility, measurable disease at baseline and at least one dose. It also excludes participants who started at 240 mg from efficacy analyses. The record does not give the size of the primary analysis population or explain how other departures from evaluability were treated.

General explanation: missing observations can affect an estimate when the chance of having an observed outcome is related to the outcome itself or to participant characteristics. Analysis-population definitions clarify which participants contribute to a result, while sensitivity analyses can explore how alternative assumptions affect it. These principles do not identify what occurred in this trial; the relevant handling details are not reported in the registry record. The stated definition and dose exclusion should therefore be kept in view when interpreting any efficacy figure, but they do not fill in the unreported missing-data or multiplicity methods.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrest (100.0%), diarrhoea (100.0%), platelet count decreased (25.0%), sepsis (12.5%), febrile neutropenia (12.5%).

The safety record separates serious adverse events, other adverse events and deaths by cohort and dose. In Cohort A at 240 mg, 6 of 8 participants at risk had a serious adverse event; in Cohort A at 160 mg, 4 of 30 did. In Cohort B at 240 mg, 1 of 1 had a serious adverse event; in Cohort B at 160 mg, 4 of 15 did. The record also reports other adverse events for all participants at risk in each listed group. Deaths are recorded as none in the Cohort A groups, 1 in Cohort B at 240 mg, and none in Cohort B at 160 mg.

These counts are descriptive and should not be read as a randomized comparison of doses or cohorts. In particular, the Cohort B 240 mg group has only 1 participant at risk in the registry record, so its count is based on a very small group. The record’s listed serious-event terms include cardiac arrest, diarrhoea, platelet count decreased, sepsis, febrile neutropenia and thrombocytopenia, with percentages attached to the terms. The basis for those term percentages is not explained in the registry record; they should not be assumed to represent participant-level risks without that definition. The registry reports a death in the Cohort B 240 mg group but does not identify its cause.

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

The record defines a clinical question: the percentage of response-evaluable participants in Cohort A with a confirmed complete or partial response under RECIST 1.1. It also establishes that the study was completed and describes a non-randomized, open-label, single-group design. Those details help readers understand what the study set out to assess and which population the primary outcome concerns.

The registry entry does not report the primary response estimate, the response count or the 80% confidence interval limits. It therefore does not show how often the specified response occurred or how precisely that frequency was estimated. Completion status and enrollment do not supply the missing outcome result. The listed secondary outcomes likewise have no numerical results in the record.

The design does not provide a randomized control comparison. Consequently, even if an outcome estimate is available elsewhere, this record’s design features alone would not establish what would have happened to comparable participants under a different treatment. The 240 mg and 160 mg groups should not be interpreted as controlled dose arms: the registry describes a dose change following a toxicity observation and excludes the 240 mg starters from efficacy analyses.

General explanation: a response percentage summarizes an observed outcome in a defined population; it is not, on its own, proof of a causal treatment effect or a complete account of benefits and harms. Interpretation also depends on the analysis population, assessment procedures, uncertainty, missing-data methods and the presence or absence of a valid comparator. Several of those details and the principal efficacy estimate are not reported in the registry record. The safest reading is therefore limited to the study’s stated question, design and recorded safety counts, without drawing conclusions about treatment efficacy.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an outcome result are not interchangeable. The registry gives a detailed definition of objective response, including the RECIST 1.1 criteria and confirmation at least 4 weeks later. It also specifies an 80% confidence interval and identifies a response-evaluable population. But it does not report the response estimate, its interval limits or the analysis count. A precise endpoint description cannot substitute for the numerical result needed to assess the observed response frequency.

The design details are also important to statistical interpretation. The study is recorded as non-randomized, single group and open label. Its dose groups are not a randomized comparison, and the efficacy analyses excluded participants who started at 240 mg after the sponsor lowered the dose in response to hematological toxicity. This makes it especially important to keep safety reporting and efficacy analysis populations distinct rather than treating all listed groups as equivalent arms.

The record also names several secondary outcomes but does not give their results or analytical details. That gap illustrates the need to distinguish registered outcomes from reported findings and to look for information about missing data, multiplicity and analysis methods. Those topics are not reported in the registry record. For statistical readers, the key lesson is to separate what the design and endpoint definition establish from what requires numerical outcome reporting. Without the primary estimate and its uncertainty, the central efficacy question remains unanswered by this record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several features of the registry record limit interpretation. The primary objective response result is not reported: there is no response percentage, response count or interval limit. Although an 80% confidence interval is specified, the record does not state the calculation method. The analysis population is defined, but its size is not reported. The record also does not report the number of participants with an assessable response or the handling of missing assessments.

The study is non-randomized, open-label and single group, with no registered control comparison. The dose groups cannot be treated as randomized comparators. The record says the sponsor lowered the dose from 240 mg to 160 mg after noting increased frequency and early onset of Grade 3 or higher hematological toxicity among participants receiving 240 mg; participants starting at 240 mg were excluded from efficacy analyses. The timing and process of dose assignment are not reported in the registry record.

The registry lists secondary outcomes but gives no corresponding outcome values in the record described. It also does not report multiplicity handling, covariate adjustment, independent response review, missing-data methods, sensitivity analyses or the statistical analysis plan. The safety record gives group counts and some serious-event terms, but the basis for the term percentages is not described. The cause of the recorded death in Cohort B at 240 mg is not reported in the registry record. These limits prevent a fuller assessment of efficacy estimates, uncertainty, group comparability and safety-event context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Investigating DNA-damage Response Agents in Molecularly Altered Advanced Cancer — NCT04564027.
• Registry record last updated 2025-08-29; status last verified 2025-08.
• Results first posted 2024-06-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry identifies PLANETTE as a completed phase 2a, multicentre, open-label study of DNA-damage response agents or combinations in advanced cancer with molecular alterations. The recorded intervention in this entry is oral ceralasertib monotherapy. The study is listed as non-randomized and single group, with enrollment of 54. Cohort A is described as ATM-altered aST and Cohort B as ATM-altered mCRPC; each cohort has listed 240 mg and 160 mg safety groups.

The primary outcome is Cohort A objective response rate, defined by confirmed complete or partial response under RECIST 1.1, with an 80% confidence interval and a timeframe of 2 years 4 months. The registry says 240 mg starters were excluded from efficacy analyses after a dose reduction. It lists seven outcome measures and no analyses. Numerical primary and secondary efficacy results, detailed analysis methods and missing-data procedures are not reported in the registry record.