PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors (NCT03685591), a non-randomized phase 1 study. The primary outcome is Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment.

2. Clinical Question

The study asked whether first-cycle dose-limiting toxicities occurred in adults receiving PF-06952229 for advanced solid tumors. It evaluated PF-06952229 as a single drug at escalating dose levels and, in prostate cancer cohorts, in combination with enzalutamide. The record describes the study as a Phase 1 dose-escalation and expansion study focused on safety, tolerability and pharmacokinetics. Its primary outcome concerns dose-limiting toxicities within the first cycle, rather than a randomized comparison of treatments.

3. Trial Design

This was a Phase 1, non-randomized, unmasked, sequential study sponsored by Pfizer. The registry lists 49 enrolled participants. It records a start date of 2018-10-04, a primary completion date of 2022-03-30, and a status of terminated. The reason for termination is not reported in the registry record.

The study had dose-escalation and expansion parts. In Part 1A, the listed monotherapy doses ranged from 20mg to 750mg twice daily. Part 1B listed prostate cancer cohorts receiving PF-06952229 at 375mg, 500mg, 625mg or 750mg twice daily in combination with enzalutamide. The registry also lists prostate cancer expansion arms at a recommended Phase 2 dose, with and without enzalutamide. The actual recommended dose is not reported in the registry record.

Sequential dose escalation is a design in which cohorts are considered in an ordered dose sequence; the registry identifies the model as sequential. The detailed escalation rules, cohort decision procedures and rationale for selecting dose levels are not reported in the registry record. The listed arms are not randomized groups, so differences between them cannot be interpreted as unbiased treatment comparisons. The registry also lists pharmacokinetic outcomes, including maximum observed plasma concentration, time to maximum concentration, and area-under-the-curve measures in Parts 1A and 1B.

The record does not report a concurrent control arm or masking. It does not report the reason for the study's termination, or whether every listed arm enrolled participants. Outcome analyses are not listed in the registry record.

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: A total of 42 participants were enrolled in the Part 1A and all were treated. A total of 7 participants were enrolled in Part 1B and all were treated.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Population included all enrolled participants who received at least one dose of investigational product and included data evaluated for a minimum DLT observation period of 28 days.

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: All enrolled participants who received at least one dose of study treatment.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment, measured over Within 28 days of first dose or until the participant completed the first cycle of therapy if there were treatment delayed (on average 28 days)..

The primary outcome counts participants with first-cycle dose-limiting toxicities (DLTs) by treatment. The registry describes DLTs as clinically significant events during the first cycle used to guide maximum tolerated dose decisions and future dose escalation or de-escalation. The stated timeframe is within 28 days of the first dose, or until completion of the first cycle if treatment was delayed; the record characterizes the average timeframe as 28 days.

The criteria include specified severe hematologic events, such as prolonged Grade 4 thrombocytopenia or neutropenia, and certain Grade 3 or 4 events involving bleeding, infection or transfusion. Nonhematologic criteria include clinically significant toxicities of Grade 3 or higher, specified liver enzyme and bilirubin elevations without another explanation, and Grade 3 nausea, vomiting or diarrhea that did not resolve within 4 days despite maximal supportive therapy. The definition also includes toxicity causing a dose delay of at least 2 weeks or preventing receipt of 75% of study drug. The registry's full criteria include further qualifications for particular events.

Counting DLTs is useful in early dose-escalation research because the frequency and type of qualifying toxicities inform decisions about tolerability and further dose evaluation. A count describes how many participants met the stated definition; by itself it does not establish a rate unless the relevant denominator is also reported. The primary outcome's observed counts and analysis are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event summarized as a count: a participant either met the registry's DLT definition during the observation period or did not. This is distinct from a continuous measure such as a concentration and from a time-to-event measure. A count answers how many qualifying events were observed among the participants assessed. To interpret that count as a frequency, the number assessed in the corresponding cohort must also be clear. The registry defines the primary population but does not report the cohort-specific primary outcome counts.

What does a DLT count represent?

Each participant is assessed against the protocol's event criteria during the first cycle. Those criteria combine event severity, duration, clinical significance and treatment consequences. This makes the endpoint a composite: several different clinical events can qualify for the same outcome. Composite endpoints can summarize multiple relevant event types, but the aggregate count does not show which criterion contributed to each participant's classification. The record gives examples and thresholds, but does not report the primary result by DLT type.

The stated observation period is within 28 days of the first dose, or until first-cycle completion if treatment was delayed, described as an average of 28 days. Comparable observation is important when counting events: participants observed for different periods may have different opportunities for an event to be recorded. The primary population description says participants had data evaluated for a minimum DLT observation period of 28 days. The handling of participants who did not complete that observation or had incomplete endpoint data is not reported in the registry record.

How should dose cohorts be compared?

In a sequential dose-escalation study, dose levels are considered in sequence rather than assigned randomly. The registry identifies this study as sequential and non-randomized. General statistical interpretation therefore differs from a randomized trial: participant characteristics, timing and treatment context may vary between cohorts, and cohort-to-cohort contrasts can be affected by those differences. The record does not report the detailed escalation algorithm, the rule for advancing or reducing a dose, or an adjusted comparison model. No randomized treatment contrast should be inferred from the dose groups.

A count can be reported with a denominator and an uncertainty interval to show the range of values compatible with the observed data under specified assumptions. A confidence interval is not a guarantee that the true value lies within its limits; it quantifies uncertainty in an estimate under the method used. The registry record reports no primary-outcome confidence intervals, proportions or hypothesis tests. No new estimate can be derived from the endpoint description alone.

What do the planning assumptions mean?

General sample-size planning uses assumptions about the significance level, allocation and effect to be detected. The planning illustration associated with these results uses a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; its target effect is described as a stated fraction of an observed effect. These are planning assumptions, not a description of the trial's own design. The registry record does not report the study's sample-size justification or its own planning assumptions. Planning estimates are illustrations of how a future study might be sized under selected assumptions, not observed power and not evidence that an effect was present.

For binary outcomes, general sample-size methods depend on the expected event frequencies in the groups and the size of the contrast to be detected. Those quantities are not reported for the primary DLT outcome. No planning estimate should be treated as a feature of the actual enrollment or as a result of this study. The registry lists 49 participants enrolled, but it does not report a primary-outcome denominator by cohort.

Why do pharmacokinetic outcomes use different summaries?

The registry lists maximum observed plasma concentration, time of maximum concentration, and area-under-the-concentration-time-profile measures. These are pharmacokinetic outcomes and are not interchangeable with the binary DLT count. Concentration and area-under-the-curve measures describe drug exposure, while time of maximum concentration describes when that maximum is observed. The registry lists these outcomes for Parts 1A and 1B, but does not report their values or analyses. The statistical summaries and models used for those outcomes are not reported in the registry record.

Adverse-event counts also require careful interpretation. A participant may experience more than one event, while the number of affected participants counts people rather than event episodes. The record's safety entries list participants at risk and participants affected, but do not provide a complete event-level analysis in the information available. General methods for handling repeated events, missing observations, covariates, or multiplicity cannot be attributed to this study because the registry record does not report them.

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("Part 1A: PF-06952229 20mg Monotherapy", "Part 1A: PF-06952229 40mg Monotherapy", "Part 1A: PF-06952229 80mg Monotherapy", "Part 1A: PF-06952229 150mg Monotherapy", "Part 1A: PF-06952229 250mg Monotherapy", "Part 1A: PF-06952229 375mg Monotherapy")
n      <- c(1, 1, 1, 4, 9, 15)
events <- c(0, 0, 0, 0, 0, 3)
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  Part 1A: PF-06952229 20mg Monotherapy  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Part 1A: PF-06952229 40mg Monotherapy  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Part 1A: PF-06952229 80mg Monotherapy  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Part 1A: PF-06952229 150mg Monotherapy  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Part 1A: PF-06952229 250mg Monotherapy  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Part 1A: PF-06952229 375mg Monotherapy  15  3  20.0  4.3  48.1  7.0  45.2  7.3  45.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including the primary DLT outcome and pharmacokinetic outcomes, but reports no analysis entries. It does not describe a statistical analysis plan, a hierarchy of endpoints, or an adjustment for testing multiple outcomes. When many outcomes are examined, the chance of at least one apparently unusual result can increase; methods such as a prespecified hierarchy or multiplicity adjustment can address that issue in some settings. This is a general statistical consideration, not a claim about methods used in this study.

Missing-data procedures are not reported in the registry record. The primary outcome population is described as enrolled participants who received at least one dose and had data evaluated for a minimum DLT observation period of 28 days. That definition does not specify how incomplete assessments, early discontinuation, or missing event information were handled. The number of participants included in the primary outcome analysis is not reported in the registry record.

The registry does not report whether outcomes were analyzed according to assigned treatment, treatment received, or another population definition beyond the stated primary population. There was no randomized assignment, and the detailed analysis populations for the dose cohorts are not reported. As a result, the enrollment count cannot be assumed to equal the number assessed for every outcome. No imputation method or sensitivity analysis is described.

These omissions matter because both missing observations and multiple outcome testing can affect how confidently results are interpreted. Without reported analysis methods and outcome counts, it is not possible to evaluate how missingness was handled or whether any reported finding accounts for multiple testing. The primary result itself is not reported in 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: anaemia (20.0%), abdominal pain (20.0%), mouth haemorrhage (20.0%), disease progression (20.0%), pneumonia (20.0%).

The safety entries list, for each cohort, the number of participants at risk and the number affected by serious adverse events, other adverse events and deaths. These are participant counts, not event counts. A participant who experiences more than one event may still contribute only once to an affected-participant count for the relevant category. The registry also lists serious-event terms with percentages: Anaemia, Abdominal pain, Mouth haemorrhage, Disease progression, Pneumonia and Hyponatraemia are each listed at 20.0%. The record does not provide further context for interpreting those term percentages in this summary.

Counts come from small cohorts in the listed safety entries. For example, the 20mg, 40mg and 80mg monotherapy cohorts each list 1 participant at risk for serious adverse events and none affected; the 150mg monotherapy cohort lists 5 at risk and 3 affected. The 250mg and 375mg monotherapy cohorts list 13 and 17 participants at risk, respectively, with 3 and 5 affected. These are descriptive counts, not randomized comparisons, and no treatment effect should be inferred from differences between cohorts.

The 150mg monotherapy cohort lists one death. The registry entry does not establish its cause or relationship to study treatment. Serious adverse events are not automatically DLTs: the primary endpoint has its own criteria and observation period, and the registry does not report which safety events met those criteria.

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

The record establishes that the study was designed to evaluate PF-06952229 in adults with advanced solid tumors, including dose escalation and expansion and combination cohorts with enzalutamide. It specifies a first-cycle DLT endpoint and the criteria used to define that outcome. It also records safety counts for the listed cohorts and pharmacokinetic outcome measures. These details describe the study's scope and the kinds of observations collected.

The record does not report primary DLT counts, primary-outcome estimates, confidence intervals or statistical analyses. It therefore cannot show how frequently DLTs occurred across the dose levels, how precisely any frequency was estimated, or how the primary result differed between cohorts. The overall enrollment of 49 does not answer those questions without the relevant analyzed denominators and event counts.

Safety counts should be interpreted as descriptive observations within non-randomized cohorts. Cohort membership was not randomized, the dose levels differ, and some cohorts received enzalutamide in combination. An apparent difference across such cohorts could reflect multiple factors and is not a controlled estimate of the effect of changing dose or adding another drug. The listed death count also does not by itself establish a cause or treatment relationship.

In general, an early-phase dose-escalation study can provide information useful for deciding which doses merit further evaluation. That general role does not mean a specific dose was selected successfully in this study: the recommended Phase 2 dose is not reported in the registry record. The record's status is terminated, but the reason is not reported. No conclusion about efficacy or treatment benefit follows from the endpoint definition or the posted safety counts alone.

The distinction is between what was planned to be measured and what results are available. The registry contains substantial endpoint definitions and design information, but its missing primary outcome results limit statistical interpretation. The information supports describing the design and recorded safety observations, not a firm estimate of DLT risk or a comparative conclusion about the treatments.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions are central to early-phase clinical research. A dose-limiting toxicity is not simply any adverse event: the registry applies criteria involving severity, duration, clinical significance and treatment interruption. Those rules determine which observations count toward a dose-escalation decision. Without the observed DLT counts, however, even a detailed definition cannot show the endpoint's frequency or precision.

The sequential, non-randomized design also shapes the statistical question. Dose cohorts support evaluation across an escalation sequence, while they do not create a randomized comparison. It is therefore important to separate descriptive cohort counts from causal claims about dose or combination treatment. The record lists monotherapy and enzalutamide combination cohorts, but no controlled comparison between them.

The study further demonstrates that a registry entry can record planned outcomes, eligibility of observations for an endpoint, and safety counts while leaving the primary analysis unavailable. Enrollment alone cannot recover the missing outcome data. Nor can serious adverse-event counts be substituted for the DLT endpoint, because the two classifications have different definitions.

Finally, the registry lists pharmacokinetic outcomes alongside safety outcomes. These measure different features of treatment: observed concentration and exposure are not equivalent to clinical toxicity. Reading those outcome families separately avoids treating a concentration measure as evidence about tolerability or efficacy. In this record, the statistical value lies chiefly in the transparent design and endpoint definitions; the absence of primary outcome analyses limits what can be concluded from the posted results.

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 limitations specific to this study restrict interpretation of its posted results. The registry does not report primary DLT outcome counts or an analysis, despite identifying DLTs as the primary outcome. It therefore provides no cohort-specific primary estimate, uncertainty interval or statistical comparison. The number enrolled is recorded as 49, but analyzed denominators for the primary outcome are not reported.

The study was non-randomized, unmasked and sequential. Dose cohorts and combination cohorts are consequently not like-for-like randomized groups. Comparisons between cohorts could reflect differences other than dose or treatment combination, and the registry does not report an adjusted analysis. The detailed escalation rules and basis for decisions to advance or de-escalate are also not reported in the registry record.

The listed safety groups cover selected dose cohorts, and the available entries do not provide the primary DLT classification for those participants. The safety counts should not be treated as DLT results. The registry lists a death in one cohort but does not report a causal assessment. It also does not report the reason the study was terminated or the actual recommended Phase 2 dose.

Methods for missing data, multiplicity, endpoint analysis and sample-size justification are not reported in the registry record. The 19 listed outcomes raise general questions about how multiple outcomes were handled, but no testing strategy is described. The record's planning assumptions do not establish the trial's own sample-size rationale. These gaps mean the posted information is insufficient to evaluate the precision, robustness or completeness of the primary endpoint findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors — NCT03685591.
• Registry record last updated 2024-06-26; status last verified 2024-06.
• Results first posted 2024-06-26.
• 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

NCT03685591 is a Pfizer-sponsored Phase 1, non-randomized, unmasked, sequential study of PF-06952229 in adults with advanced solid tumors. It lists 49 participants enrolled, a start date of 2018-10-04, a primary completion date of 2022-03-30, and a terminated status. The study included dose escalation and expansion, with monotherapy cohorts and prostate cancer cohorts combining PF-06952229 with enzalutamide.

The primary outcome was the count of participants with first-cycle DLTs by treatment, assessed within the stated first-cycle observation period. The registry defines qualifying toxicities but does not report primary outcome counts or analyses. Safety entries report cohort-level counts of participants at risk and affected, along with one death in the 150mg monotherapy cohort. The reason for termination, recommended Phase 2 dose, detailed statistical plan and missing-data methods are not reported in the registry record.