A Study Of PF-06647020 For Adult Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Of PF-06647020 For Adult Patients With Advanced Solid Tumors (NCT02222922), a non-randomized phase 1 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs) - Q3W Regimen.

2. Clinical Question

The registry describes a first-in-human Phase 1 study in adults with advanced solid tumors. Its central statistical task was descriptive: count DLTs under the specified first-cycle definition across escalating doses. This endpoint was intended to support dose selection, rather than to estimate a comparative treatment effect against a control arm.

The study also included pharmacokinetic outcomes and additional regimens, including Q2W dosing, fluconazole, and Avelumab. These components address different questions from the primary Q3W DLT outcome. The registry lists outcomes involving PF-06647020 concentration and disposition, but numerical results for them are not reported in the registry record.

3. Trial Design

This was a completed, non-randomized, unmasked Phase 1 study sponsored by Pfizer. The registry reports enrollment of 138 participants. The study started on 2014-10-17, and primary completion was 2019-11-05. Its stated objective was to assess safety and tolerability at increasing dose levels, determine the maximum tolerated dose, and select a recommended Phase 2 dose.

The registry describes several treatment arrangements. PF-06647020 was infused over 60 minutes once every 21 days in the Q3W regimen, and over 60 minutes once every 14 days in the Q2W regimen, described as a 28 day cycle. Other listed arrangements paired PF-06647020 with fluconazole for a drug-drug interaction assessment or combined PF-06647020 with Avelumab. The primary outcome applies specifically to the Q3W dose-escalation regimen; it should not be treated as an outcome shared by all regimens.

Because allocation was non-randomized and masking was absent, dose groups do not function as randomized comparison arms. Participants entered different dose levels or regimens as part of the study design, and the registry does not establish that those groups were otherwise exchangeable. Differences across groups could reflect dose, regimen, participant characteristics, or other factors; a causal comparison between groups is not supported by the design description.

The registry reports 86 outcome measures and 12 analyses. Detailed results for the primary endpoint and the listed pharmacokinetic outcomes are not reported in the registry record. The study’s protocol-level dose-escalation rules, allocation procedures beyond the non-randomized designation, and statistical analysis plan are not reported in the registry record. The enrollment figure is the study-wide total and does not specify the number evaluated for the Q3W primary outcome.

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: Once every 3 weeks (Q3W) Regimen: A total of 113 participants were enrolled to study treatments and 1 participant in the PF-06647020 2.1 mg/kg treatment group didn't receive any study treatment. Once every 2 weeks (Q2W) Regimen: A total of 25 participants were enrolled to study treatments and all were treated with study drug.

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: Participants enrolled in the dose escalation phase in Q3W regimen who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle with a baseline disease assessment and at least 1 post-baseline disease assessment.

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: Baseline analysis population included all enrolled participants who received at least 1 full or partial dose of study medication.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs) - Q3W Regimen, measured over First Cycle, Day 1 up to Day 21.

The primary endpoint counts participants with dose-limiting toxicities in the Q3W regimen during the first cycle, from Day 1 up to Day 21. A DLT was defined using specified hematologic, hepatic, and other major-organ toxicity criteria, along with treatment delay attributable to PF-06647020. The definition also allowed the first-cycle observation period to extend until a participant received a second infusion when treatment was delayed.

For hematologic events, the criteria included Grade 4 neutropenia lasting >7 days, febrile neutropenia, Grade >=3 neutropenic infection, Grade 4 anemia, and Grade >=3 thrombocytopenia with clinically significant bleeding. Hepatic criteria included Grade >=3 serum bilirubin, hepatic transaminase, or alkaline phosphatase, and specified concurrent ALT or AST and bilirubin elevations. Other qualifying events included Grade >=3 non-hematologic, non-hepatic major-organ toxicities and a delay of >2 weeks in the next scheduled cycle due to persisting toxicities attributed to PF-06647020.

This type of endpoint is used in dose-escalation research to summarize clinically important toxicity during a defined early treatment window. It can inform assessment of tolerability and dose selection, but a count alone does not establish the safety profile over all treatment cycles or compare outcomes with an untreated or randomized control group. Participants needed to be on study for at least 21 days to be evaluable; those who ended participation earlier could be replaced. The number of participants with DLTs and the evaluated denominator are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: each eligible participant either met the DLT definition during the specified first-cycle window or did not. For a binary outcome, a count describes how many participants experienced the event. Interpretation also requires the number of participants assessed, because a count alone does not show how common the event was in that group. Neither the primary count nor its evaluated denominator is reported in the registry record.

Why define a DLT window?

In dose-escalation research, restricting the endpoint to an early treatment period provides a consistent window for identifying toxicities relevant to dose selection. The registry defines this window as First Cycle, Day 1 up to Day 21, with allowance for treatment delays until a second infusion. It also specifies event categories and severity thresholds. A prespecified definition helps make event classification more consistent, although the adjudication process and handling of borderline cases are not reported in the registry record.

The endpoint includes several clinically distinct event types: hematologic, hepatic, other major-organ toxicities, and treatment delays attributed to the investigational drug. Combining these types into one DLT outcome supports a broad dose-limiting safety summary, but it does not show which event type occurred unless separate component results are also reported. Component-level DLT results are not reported in the registry record.

What does a confidence interval convey?

General explanation: a confidence interval describes statistical uncertainty around an estimated quantity under a specified method. For a binary event rate, a wider interval generally indicates less precision, often because the available number of observations or events is limited. An interval does not remove limitations in the study design, and it does not address whether groups are comparable. No confidence interval for the primary DLT outcome is reported in the registry record.

Why does non-randomization matter?

General explanation: random allocation can help balance known and unknown participant characteristics across treatment groups. Without randomization, dose groups may differ for reasons other than dose. In a dose-escalation study, group sizes and participant composition may also differ across levels. Therefore, a contrast between groups is descriptive unless a suitable design and analysis support a causal interpretation. The registry labels allocation as non-randomized and does not report an adjusted comparative analysis for the primary endpoint.

How should the safety counts be read?

The adverse-event record presents counts of participants at risk and participants affected, separately for serious and other adverse events, along with deaths. These are descriptive counts for each listed dose group. The at-risk count provides essential context for the affected count; raw counts across groups cannot be compared without considering their different denominators. General explanation: percentages or rates can aid comparison of frequency, but they do not correct for confounding or differences in follow-up. The duration of follow-up for the adverse-event summaries and the rules for attributing events are not reported in the registry record.

Over-dispersion is a general concern for count data when variation exceeds what a simple model assumes. It matters when a count-model analysis is used, because underestimated variation can make uncertainty appear too small. The primary endpoint is described as a count of participants with an event, but the registry information does not identify a count model or report a dispersion parameter. It would be inappropriate to assume that a particular model or over-dispersion correction was used.

What do the planning illustrations mean?

General explanation: sample-size planning asks how many participants would be needed under stated assumptions to detect a specified effect with a chosen statistical procedure. The illustrations associated with this study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. They are planning illustrations, not observed trial results or observed power. The registry record does not report the primary DLT estimate needed to understand the observed-effect basis, nor does it report that these assumptions were the trial’s original design justification. The trial’s own sample-size justification is not reported in the registry record.

The registry reports 12 analyses and 86 outcome measures, but the number of listed analyses alone does not reveal which statistical methods were used, how uncertainty was handled, or whether comparisons were adjusted. Those details are not reported in the registry record. Numerical results for the primary endpoint and pharmacokinetic measures are also not reported in the registry record, so no effect estimate, p-value, or interval can be interpreted from the record information described.

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("PF-06647020 0.2 mg/kg（Q3W Regimen）", "PF-06647020 0.5 mg/kg (Q3W Regimen)", "PF-06647020 1.25 mg/kg (Q3W Regimen)", "PF-06647020 2.1 mg/kg (Q3W Regimen)", "PF-06647020 2.8 mg/kg (Q3W Regimen)", "PF-06647020 3.7 mg/kg (Q3W Regimen)")
n      <- c(2, 2, 2, 4, 15, 6)
events <- c(0, 0, 0, 0, 0, 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  PF-06647020 0.2 mg/kg（Q3W Regimen）  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  PF-06647020 0.5 mg/kg (Q3W Regimen)  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  PF-06647020 1.25 mg/kg (Q3W Regimen)  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  PF-06647020 2.1 mg/kg (Q3W Regimen)  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PF-06647020 2.8 mg/kg (Q3W Regimen)  15  0  0.0  0.0  21.8  0.0  20.4  0.2  20.6
ARM  PF-06647020 3.7 mg/kg (Q3W Regimen)  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The registry reports 86 outcome measures and 12 analyses, indicating that the study recorded multiple outcomes and analyses. The registry record does not report whether hypotheses were organized into a hierarchy, whether any outcomes were designated for confirmatory testing, or whether multiplicity adjustments were planned or performed. Without that information, the number of analyses should not be taken as evidence that statistical error was controlled in a particular way.

The primary DLT endpoint has an eligibility definition requiring participants to receive at least 1 dose, avoid major first-cycle treatment deviations, and have baseline and post-baseline disease assessments. Participants ending study participation before 21 days could be replaced. The number excluded, replaced, or evaluated for this outcome is not reported in the registry record. The approach to missing DLT observations, incomplete follow-up, or other missing outcome data is also not reported in the registry record.

For the safety summaries, the registry supplies at-risk counts and affected counts by listed dose group. It does not specify the follow-up duration or how incomplete adverse-event reporting was handled. The primary analysis population is described, but the analysis population used for each other outcome is not reported in the registry record. These gaps matter because the population included in an analysis can influence both the event counts and their interpretation.

There is no basis in the registry information to infer imputation methods, sensitivity analyses, interim analyses, or stopping criteria. These methods are not reported in the registry record. The sample-size illustrations use stated planning assumptions, but they do not establish the study’s original justification, missing-data strategy, or multiplicity plan.

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: diarrhoea (33.3%), vomiting (25.0%), headache (25.0%), abdominal pain (20.0%), constipation (16.7%).

The safety record lists serious adverse events, other adverse events, and deaths by dose group. For each group, the at-risk count is reported alongside the number of participants affected. For serious events, the records include groups ranging from PF-06647020 0.2 mg/kg (Q3W Regimen) to PF-06647020 3.7 mg/kg (Q3W Regimen), as well as Q2W groups. The affected counts differ across groups, and the at-risk counts also differ. Read each count within its own group rather than treating raw counts as directly comparable.

The record lists 13 deaths in PF-06647020 2.8 mg/kg (Q3W Regimen) and 2 in PF-06647020 3.2 mg/kg (Q2W Regimen); it lists 0 deaths in the other reported groups. These are descriptive registry counts. The record does not establish that the investigational drug caused these deaths, and the non-randomized design does not support a like-for-like comparison between dose groups.

The listed serious-event terms include Diarrhoea, Vomiting, Headache, Abdominal pain, Constipation, and Mental status changes, each with a registry percentage. The denominator and context for those percentages are not reported in the registry record. These terms should not be interpreted as rates for every enrolled participant without that context. Follow-up duration and event-attribution details are also not reported in the registry record.

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

The study was designed to assess safety and tolerability across increasing PF-06647020 doses and to support selection of a maximum tolerated dose and recommended Phase 2 dose. The primary endpoint was a count of participants with DLTs during the first cycle in the Q3W dose-escalation regimen. However, the primary outcome count and evaluated population size are not reported in the registry record. Therefore, the posted information does not establish the frequency of DLTs or identify a dose level based on that endpoint.

The safety data provide descriptive counts of serious adverse events, other adverse events, and deaths for the listed groups. These counts should be considered in light of the different numbers at risk and the non-randomized design. They do not establish comparative risk or prove that a treatment caused an event. The record’s serious-event terms provide additional descriptive detail, but their denominator and reporting context are not reported in the registry record.

The study’s registry description does not provide numerical results for the listed pharmacokinetic outcomes. Thus, the available information cannot quantify exposure, clearance, or other measures of drug disposition. It also does not provide a clinical efficacy result that could support a conclusion about tumor response or patient benefit.

General explanation: a Phase 1 dose-escalation study has a different purpose from a randomized efficacy trial. Early safety and pharmacokinetic assessment can inform later research, but it is not by itself a controlled test of clinical benefit. Here, the non-randomized allocation, lack of masking, and unavailable primary endpoint result limit what can be inferred. The registry record also does not report the statistical analysis plan, missing-data methods, or sample-size justification, so those methods cannot be evaluated.

The enrollment total of 138 is not the primary endpoint denominator. It covers the study overall, including multiple regimens, while the primary outcome definition is specific to eligible Q3W dose-escalation participants. The number evaluated for that outcome is not reported in the registry record. No conclusion about DLT frequency, dose-response, or treatment effect should be drawn from total enrollment alone.

14. Why This Trial Matters Statistically

This study illustrates why a dose-escalation endpoint must be interpreted with its population and observation window. A DLT count is meaningful only when the event definition, follow-up interval, and number evaluated are clear. The registry describes the first-cycle criteria in detail, including hematologic and hepatic thresholds, other organ toxicities, and treatment delays. Yet the DLT count and denominator are not reported in the registry record, leaving the primary safety question unanswered in the available numerical information.

It also highlights the distinction between a study-wide enrollment total and an endpoint-specific analysis population. The 138 participants were enrolled across a study with Q3W, Q2W, drug-drug interaction, and combination components. The primary endpoint concerns eligible participants in the Q3W dose-escalation regimen. Treating total enrollment as the DLT denominator would therefore be unjustified.

Non-randomized dose groups require careful descriptive interpretation. Different group sizes and participant profiles can make raw event counts look different even when the underlying risks are not directly comparable. The safety summaries list at-risk and affected counts by group, which supports group-specific reading, but the design does not create randomized controls. The registry record does not report an adjusted comparison that would address these limitations.

Finally, the study shows how extensive outcome registration does not necessarily provide enough detail to assess statistical inference. The record lists 86 outcome measures and 12 analyses, but numerical primary results, multiplicity procedures, missing-data methods, and the statistical plan are not reported in the registry record. A careful statistical reading separates what is documented—the design, endpoint definition, and descriptive safety counts—from conclusions that require unreported estimates or methods.

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 principal limitation for interpreting the primary endpoint is that the registry record does not report the DLT count or the number evaluated. Although the endpoint definition and first-cycle window are described, without these numbers the primary result cannot be quantified or assessed for precision. The total enrollment of 138 does not resolve this gap because the primary outcome population was restricted to eligible participants in the Q3W dose-escalation phase.

The non-randomized, unmasked design limits comparisons across dose levels and regimens. Groups may differ in size and participant characteristics, and the record does not report an adjusted comparative analysis. It would therefore be inappropriate to attribute differences in adverse-event counts to dose alone. The groups should be read as descriptive safety summaries rather than randomized treatment comparisons.

The registry lists serious adverse-event terms and percentages, but the denominator and context for the percentages are not reported in the registry record. Follow-up duration, event-attribution rules, and handling of incomplete adverse-event information are also not reported. Those omissions restrict interpretation of the safety summaries, particularly when comparing groups with different at-risk counts.

Numerical results for the listed pharmacokinetic outcomes and the statistical analysis plan are not reported in the registry record. The specific dose-escalation rules, sample-size justification, interim analysis procedures, missing-data methods, and multiplicity strategy are also not reported in the registry record. Consequently, the precision and analysis choices behind the study’s stated dose-selection objective cannot be evaluated from the recorded details.

The registry lists a broad set of outcomes, but the presence of outcome names does not establish that complete results are available for each one. No clinical efficacy result is reported in the information described, and safety or pharmacokinetic outcomes alone do not establish comparative clinical benefit.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Of PF-06647020 For Adult Patients With Advanced Solid Tumors — NCT02222922.
• Registry record last updated 2020-12-17; status last verified 2020-12.
• Results first posted 2020-12-17.
• 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

NCT02222922 is a completed, non-randomized, unmasked Phase 1 study sponsored by Pfizer, with enrollment of 138 adults with advanced solid tumors. The study started on 2014-10-17, and primary completion was 2019-11-05. Its objective was to assess safety and tolerability at increasing doses of PF-06647020 to inform dose selection.

The primary outcome was the number of participants with DLTs in the Q3W regimen during the first cycle. The registry defines the outcome and eligible population, but the DLT count and evaluated denominator are not reported in the registry record. Descriptive adverse-event and death counts are listed for dose groups; the design does not support treating them as randomized comparisons. Numerical pharmacokinetic results, the statistical analysis plan, and details of missing-data and multiplicity handling are not reported in the registry record.