Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8) (NCT04105010), a non-randomized phase 1, phase 2 study. The primary outcome is Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC).

2. Clinical Question

This clinical question focuses on whether tumor response was observed under the study’s specified assessment rules. It is descriptive rather than a randomized comparison of treatment with a control. The non-randomized design and the defined response-evaluable population matter when interpreting any estimate: it would describe the assessed participants, not establish how outcomes compare with another treatment or with no treatment.

3. Trial Design

This completed study, NCT04105010, is described as a multinational, open-label Phase I/II investigation of AZD4205 monotherapy in patients with PTCL who had relapsed from, or were refractory or intolerant to, standard systemic treatment. The registry lists 171 participants enrolled. The recorded start date is 2019-09-10, the primary completion date is 2023-10-12, and the study status is completed.

The design was non-randomized and sequential, with no masking. In Phase 1, participants were to enter two dose-ascending cohorts, with additional participants potentially enrolled to explore a selected dose. The brief summary describes around 20~40 participants across the ascending cohorts and additional 10~20 for selected-dose exploration. Phase 2 was planned as a pivotal, single-arm, open-label assessment at the recommended Phase 2 dose. The overall enrollment figure does not specify how participants were distributed among phases or dose cohorts.

The primary outcome was Phase 2 CT-based objective response rate (ORR), assessed by an independent review committee (IRC). The primary population was defined as dosed participants with centrally confirmed PTCL and measurable baseline disease, assessed by IRC using CT imaging. Other listed outcomes include adverse events and additional response and time-to-event measures, including duration of response, complete response rate, progression-free survival, and time to response. Some outcomes were assessed by the IRC and others by investigators.

The arm descriptions use the name golidocitinib, whereas the study title and summary identify AZD4205. The registry record does not explain this naming difference. It also does not report the actual dose values, the number assigned to each cohort, or the numerical primary endpoint result.

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: 171 enrolled participants met inclusion criteria and received study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable for CT-based Response Set (all dosed and central pathology confirmed Peripheral T Cell Lymphoma (PTCL) patients with baseline measurable disease assessed by IRC using CT imaging)

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 (all patients treated with at least one dose of AZD4205)

6. Primary Endpoint

The registry lists the primary outcome as Part B: CT-based Objective Response Rate (ORR) by Independent Review Committee (IRC), measured over Up to approximately 3 years.

The primary endpoint is the percentage of participants in the Phase 2 CT-based response-evaluable population who had at least one visit with a complete response or partial response. Response was determined from CT scans by an independent review committee using Lugano criteria. The stated timeframe is up to approximately 3 years.

ORR is a binary response measure at the participant level: a participant is counted as having a response if the qualifying complete or partial response occurs, and the endpoint expresses the responding participants as a percentage of the defined population. It provides a way to describe tumor shrinkage meeting prespecified response categories without requiring every participant to have the same length of follow-up. It does not, by itself, describe how long a response lasts; duration of response is listed separately among the secondary outcomes.

Independent review is intended to apply assessment criteria separately from the treating investigator’s assessment. That can reduce dependence on a single local interpretation, although the registry record does not detail reviewer procedures or how disagreements were handled. The endpoint definition is specific about imaging modality, response categories, review body, and analysis population.

The record specifies the endpoint’s dispersion measure as a 95% confidence interval, but it does not report the response percentage, its numerator or denominator, or the interval limits. Consequently, the endpoint can be described from the registry definition, but its observed magnitude and precision cannot be evaluated from the numerical results recorded there.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary endpoint is a binary participant-level outcome summarized as a percentage: whether each participant had at least one qualifying complete or partial response. For this kind of endpoint, the response percentage is calculated from the number of participants meeting the response definition relative to the analysis population. The registry record names the response-evaluable population but does not give its size or the number of responders, so the percentage cannot be reconstructed from the recorded information.

What does the confidence interval describe?

In general, a confidence interval expresses the sampling uncertainty around an estimated quantity. For a response percentage, it indicates a range of values compatible with the observed data under the interval method’s assumptions. A point estimate without an interval can obscure uncertainty, especially when the amount of information is limited; an interval communicates precision as well as the estimated magnitude. Here, the endpoint description specifies a 95% confidence interval, but neither its limits nor the associated response estimate are reported. The method used to construct the interval is also not reported in the registry record.

Why does the analysis population matter?

The primary population is not simply all enrolled participants. It consists of those who were dosed, had centrally confirmed PTCL, had measurable baseline disease, and were assessed by IRC using CT imaging. Restricting an endpoint to participants with evaluable assessments can make the endpoint definition operationally clear, but the number excluded and the reasons for exclusion matter to interpretation. If evaluability is related to prognosis or treatment experience, the observed percentage among evaluable participants might not represent the enrolled group. The registry record does not report participant flow into this population, missing assessment handling, or sensitivity analyses.

What can the non-randomized design establish?

In general, random allocation helps balance measured and unmeasured baseline characteristics across comparison groups, while masking can reduce some forms of assessment or behavior bias. This study is listed as non-randomized and unmasked, and its Phase 2 part is described as single-arm. The response endpoint can therefore describe outcomes in the treated, assessed population, but the design does not furnish a randomized control comparison. Changes over time, selection into the evaluable set, and other influences cannot be separated from treatment effects by a single-arm estimate alone. The record does not report an adjusted comparative analysis that would address these issues.

Why distinguish the dose cohorts?

The sequential Phase 1 design included ascending dose cohorts and a selected-dose cohort, followed by Phase 2 at the recommended Phase 2 dose. These groups reflect different stages and dose choices in the study, not randomized arms. Group outcomes may differ for reasons other than dose, including the sequential enrollment process and differences in who entered each cohort. The record does not report cohort-specific primary response estimates or methods for comparing cohorts. Treating the cohort figures as if they came from a randomized head-to-head comparison would therefore overstate what the design can establish.

What is multiplicity and why is it relevant?

In general, multiplicity arises when investigators conduct several statistical tests or examine multiple endpoints, subgroups, or time points. With more opportunities to declare a result, the chance of at least one chance finding can increase unless the analysis plan addresses that issue. The registry lists 15 outcome measures and one analysis, but it does not report a multiplicity adjustment, testing hierarchy, or detailed statistical analysis plan. The count of listed outcomes alone does not establish which were formally tested, how they were ordered, or whether any adjustment was made.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such assumptions are general planning inputs, not evidence of observed power and not a substitute for the trial’s own design justification. The record does not report the effect value used, a sample-size justification for this study, or a resulting planning sample size. No new sample-size calculation can be inferred from the information recorded.

Statistical interpretation also depends on whether the response assessments and follow-up were complete, whether definitions were applied consistently, and whether the analysis population was specified before results were known. The registry record does not report the detailed statistical methods for the primary endpoint, the approach to missing data, the handling of protocol deviations, or any interim analyses. Those omissions prevent a fuller assessment of analytic choices beyond the endpoint definition and design characteristics stated in the record.

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("AZD4205 Group D")
n      <- c(102)
events <- c(44)
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  AZD4205 Group D  102  44  43.1  33.4  53.3  33.9  52.8  33.9  52.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 15 outcome measures, including the primary Phase 2 IRC-assessed ORR and secondary safety, response, and time-to-event outcomes. It lists one analysis, but does not report a testing hierarchy, multiplicity adjustment, or a statistical analysis plan explaining which outcomes were confirmatory and how repeated testing was handled. The number of listed outcomes alone does not establish that every measure was tested as a separate hypothesis.

The primary analysis population is defined as participants who were dosed, had centrally confirmed PTCL, had measurable baseline disease, and were assessed by IRC using CT imaging. This definition helps identify whose response percentage the endpoint is intended to describe. However, the record does not report the size of this population, its relationship to all enrolled participants, the number with missing or unevaluable scans, or the reasons for any exclusions.

The missing-data method is not reported in the registry record. It is therefore unclear how absent assessments, withdrawal, or other incomplete outcome information were treated in the primary analysis. No sensitivity analysis for missing response data is described. The record also does not provide details of interim analyses, adjustment for protocol deviations, or whether the primary analysis population was defined before outcomes were examined.

These are not merely technical details: analysis population choices and missing-data assumptions can affect a response percentage and its uncertainty. In the absence of reported methods and numerical endpoint results, the robustness of the primary estimate cannot be assessed from the registry record.

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: pneumonia (18.8%), covid-19 pneumonia (14.3%), oropharyngeal pain (14.3%), pyrexia (7.1%), interstitial lung disease (7.1%).

The registry lists serious adverse event counts, counts for other adverse events, and deaths separately for four treatment groups. For serious adverse events, the record gives 28 participants at risk and 12 affected in Group A; 16 at risk and 9 affected in Group B; 7 at risk and 1 affected in Group C; and 120 at risk and 44 affected in Group D. For other adverse events, the respective at-risk and affected counts are 28 and 26, 16 and 16, 7 and 6, and 120 and 114. The listed death counts are 3, 2, 1, and 54, respectively.

These are descriptive counts, not a randomized comparison. The groups differ in size and arise from a non-randomized, sequential study, so raw counts should not be read as direct evidence that one group was safer than another. The registry also lists serious-event terms with percentages: Pneumonia, 18.8%; COVID-19 pneumonia, 14.3%; Oropharyngeal pain, 14.3%; Pyrexia, 7.1%; Interstitial lung disease, 7.1%; and Pneumocystis jirovecii pneumonia, 7.1%. The denominator and group attribution for these term percentages are not reported in the registry record.

These figures do not by themselves establish whether an event was caused by treatment. The registry record does not provide exposure-adjusted event rates or comparative causal analyses.

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

The registry record establishes that a Phase I/II study of AZD4205 monotherapy in PTCL was completed and describes its non-randomized, open-label, sequential design. It also defines the primary endpoint: Phase 2 CT-based ORR assessed by an IRC under Lugano criteria in a specified response-evaluable population. These details clarify what the study set out to measure and whose outcomes were intended for the primary analysis.

The record does not report the numerical primary endpoint result. There is no ORR estimate, responder count, denominator, or 95% confidence interval. As a result, the observed frequency of response and the precision of that estimate cannot be evaluated. The endpoint definition is not a substitute for the missing result.

Even with an estimate, the single-arm Phase 2 design would describe outcomes in the treated and assessed population rather than provide a randomized comparison. It would not, by itself, show how outcomes would have differed under another treatment or no treatment. Non-random allocation and the defined response-evaluable population also mean that selection and other differences could affect interpretation. No comparative primary effect estimate is reported.

The safety counts and listed serious-event terms provide descriptive information from the registry record. They should not be treated as evidence of comparative risk or attribution, particularly because the groups differ in size and were not formed through random allocation. The record does not state the denominator for the listed serious-event term percentages.

Accordingly, the study record is useful for understanding the planned question, endpoint definition, design, and recorded safety counts. It does not establish a quantitative primary response result, its uncertainty, or a causal comparison. Those conclusions remain unavailable from the information reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and a numerical result are both necessary for statistical interpretation. The record specifies a response measure, assessment modality, review committee, response criteria, analysis population, and confidence-interval level. That information makes the target quantity understandable. But without the actual response estimate and interval, readers cannot judge either the magnitude of the observed response or how precisely it was estimated.

The design also highlights a distinction between describing outcomes and estimating comparative effects. Sequential dose cohorts and a single-arm Phase 2 component can contribute descriptive evidence about participants treated in the study. They do not create the randomized comparison needed to interpret differences as treatment effects without substantial additional assumptions. Cohort labels alone do not make groups comparable.

Defining the analysis population is another important statistical feature. The primary endpoint concerns dosed participants with centrally confirmed disease, measurable baseline disease, and IRC assessment. That is more specific than the overall enrollment count. Transparent reporting of the number entering this population, the completeness of assessments, and the missing-data approach would help readers understand how representative the endpoint estimate is.

Finally, the record lists several outcomes and safety measures but does not describe multiplicity handling or detailed analysis methods. Such information matters because selective testing, missing observations, and analysis choices can influence how much confidence to place in results. The registry record allows the study’s statistical structure to be identified, while also showing where reported results and methods are insufficient for a fuller evaluation.

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.

The most direct limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. Although the endpoint description specifies a 95% confidence interval, neither the estimate nor the interval limits appear. The responder count and analysis denominator are also absent, preventing independent reconstruction or assessment of precision.

The registry lists 171 participants enrolled but does not report how they were distributed between the Phase 1 and Phase 2 parts or among the four described groups. The primary endpoint is restricted to a response-evaluable population, yet the number meeting that definition and the reasons participants may not have been evaluated are not reported. The missing-data method is also not reported.

The study was open-label, non-randomized, and sequential. The Phase 2 part was planned as single-arm, and no randomized control group is described. These design features limit causal and comparative interpretation. Differences among dose cohorts cannot be treated as randomized dose effects.

The registry record does not report the actual dose values, the detailed statistical analysis plan, methods for constructing the confidence interval, multiplicity procedures, or interim-analysis details. It also does not identify the denominator or group attribution for the listed serious-event term percentages. Finally, study materials use AZD4205 in the title and summary but golidocitinib in the arm descriptions; the record does not explain the naming difference.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessing An Oral Janus Kinase Inhibitor, AZD4205 as Monotherapy in Patients Who Have PTCL (JACKPOT8) — NCT04105010.
• Registry record last updated 2025-04-04; status last verified 2025-04.
• Results first posted 2025-04-04.
• 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

NCT04105010 is a completed, multinational, open-label, non-randomized Phase I/II study in relapsed or refractory PTCL. The registry lists 171 participants enrolled and describes sequential dose cohorts in Phase 1 followed by a single-arm Phase 2 study at the recommended Phase 2 dose. The primary endpoint was Phase 2 CT-based ORR assessed by an IRC under Lugano criteria in a defined response-evaluable population, with a 95% confidence interval specified.

The registry record does not report the numerical ORR result, its denominator, or its confidence interval. It lists adverse-event counts by group and several serious-event terms, but does not report the denominator for those term percentages. The non-randomized, single-arm design does not provide a randomized comparative treatment effect.