A Study of PF-06873600 in People With Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of PF-06873600 in People With Cancer (NCT03519178), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs) - Part 1.

2. Clinical Question

This was a dose-finding and expansion study, not a randomized test of PF-06873600 against a control treatment. Its main early question concerned tolerability of the study medicine, used alone or with endocrine therapy. The registry record also identifies pharmacokinetic and pharmacodynamic objectives and anti-tumor activity among the study’s broader interests. Those objectives do not turn the nonrandomized treatment groups into direct comparative evidence.

The eligible cancer types span several disease settings. The registry record names hormone receptor-positive and HER2-negative metastatic breast cancer, triple-negative breast cancer, male breast cancer, ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. The brief summary describes additional eligibility in terms of advanced or metastatic HER2-negative breast cancer and epithelial ovarian cancer. It does not report outcome results separately for these populations in the registry record for this analysis.

Some participants were assigned to receive endocrine therapy with PF-06873600. The brief summary identifies letrozole and fulvestrant as options. The registry record does not report a randomized comparison between these options, or between combination therapy and PF-06873600 alone. The relevant interpretation is therefore descriptive: the primary endpoint concerns observed dose-limiting toxicities during the first cycle, while the study’s broader aims include evaluating safety, drug exposure, and anti-tumor activity.

3. Trial Design

The registry record describes a phase 1/2a study with dose escalation and dose expansion. It began on 2018-03-07, had a primary completion date of 2023-04-05, and is listed as terminated. The record does not explain the reason for termination. These registry dates and status describe the study record; they do not, by themselves, establish the completeness or interpretation of any endpoint results.

Allocation was nonrandomized, masking was none, and the study model was sequential. Participants entered different dose or treatment groups as the study proceeded. The listed groups include single-agent PF-06873600 dose-escalation groups, combination dose-finding groups with endocrine therapy, and expansion groups using PF-06873600 alone or in combination. These groups represent different doses, schedules, treatment combinations, and study parts. They should not be treated as though participants had been randomly assigned to comparable arms.

The brief summary says participants took PF-06873600 by mouth at home, one to two times a day, with the dose subject to change. Some participants also received endocrine therapy: letrozole by mouth or fulvestrant by injection. Clinic visits were described as weekly during the first two cycles and every cycle thereafter. Participants were expected to take part for at least 7 to 8 months, depending on response. These procedures describe the planned study experience, not the observed duration or adherence of individual participants.

The registry record lists Pfizer as sponsor and enrollment of 155. That enrollment figure should not be assumed to be the denominator for the primary endpoint: the endpoint population was restricted to participants who received at least one dose and had no major treatment deviations during the first cycle. The number meeting that definition is not reported in the registry record. Nor does the record establish that every enrolled participant contributed to every treatment group or outcome.

Because the design was sequential and nonrandomized, dose selection and expansion are central to understanding the group structure. Differences between groups could reflect dose, schedule, combination treatment, study part, or participant mix. Without random assignment and a stated adjustment strategy, a simple contrast between arms would not isolate a treatment effect. The record does not report a planned causal comparison between 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: Primary outcome measures and secondary outcome measures analysis was final at primary completion date milestone and reported on the same milestone.

Only the first 6 of 15 groups are shown.

PF-06873600 Treatment

Reasons for not completing this period:

Fulvestrant. Treatment

Reasons for not completing this period:

Letrozole Treatment

Reasons for not completing this period:

Follow-Up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis population consisted of all enrolled participants who received at least 1 dose of study intervention and who did not have major treatment deviations during the first cycle (ie, evaluable for the maximum tolerated dose \[MTD\]).

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: Analysis population consisted of all enrolled participants who received at least 1 dose of study intervention.

Only the first 6 of 16 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs) - Part 1, measured over Cycle 1 (within 28 days after the first dose of study intervention).

The primary endpoint is the number of participants with dose-limiting toxicities in Part 1, assessed during Cycle 1, within 28 days after the first dose of study intervention. The registry definition covers specified serious blood-related and non-blood-related adverse events that were attributed to one or both study agents. The endpoint is a count of participants meeting the dose-limiting-toxicity definition, rather than a measure of tumor response or drug concentration.

In general, dose-limiting toxicity is used in early dose-finding research to identify toxicity that constrains further dose escalation. Observing these events during a defined treatment period gives investigators a consistent window for evaluating tolerability. It can inform decisions about which doses or schedules merit further study, although the registry record does not report the decision process or a maximum tolerated dose result.

The primary analysis population was defined as enrolled participants who received at least one dose and did not have major treatment deviations during the first cycle, making them evaluable for the maximum tolerated dose. This is narrower than the enrollment population. The record does not report how many participants met the definition or the endpoint count for any dose group. Accordingly, the endpoint’s stated purpose and definition can be described, but the observed frequency of dose-limiting toxicity cannot be assessed from the registry information.

As a general statistical point, a count is most interpretable alongside its denominator and a clear population definition. The record specifies the intended population rule but does not give the number analyzed or the endpoint results. It therefore does not support estimating a toxicity proportion or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event expressed as a count: whether each evaluable participant experienced a dose-limiting toxicity during the specified period. This differs from a continuous measure, such as a laboratory value, and from a time-to-event outcome, such as time until progression. For a binary outcome, a count is commonly interpreted with a denominator so that the observed frequency can be understood in relation to the number assessed. The registry record gives the population rule but does not report the analyzed denominator or the primary endpoint count.

What does the endpoint count represent?

The endpoint counts participants meeting the protocol’s DLT definition, not every adverse event recorded during treatment. A participant could have more than one event, but a participant-level count ordinarily concerns whether the participant met the endpoint definition. The definition specifies the relevant event types, attribution, and first-cycle assessment window. Those boundaries matter: events outside the window or events that do not meet the definition are not automatically part of this primary endpoint. The registry record does not report participant-level event details, so the endpoint cannot be reconstructed from the general serious adverse-event counts.

Why does the analysis population matter?

The stated primary population includes enrolled participants who received at least one dose and had no major treatment deviations during the first cycle. This restriction makes the endpoint specific to participants considered evaluable for maximum tolerated dose. It also means that the enrollment figure is not necessarily the number used in the primary analysis. If participants are excluded from an endpoint population, the number and reasons for exclusion help readers assess how the analyzed group differs from the enrolled group. The number meeting this endpoint definition and the reasons for any exclusions are not reported in the registry record.

What can a confidence interval add?

In general, a confidence interval describes the statistical uncertainty around an estimate under the method used to calculate it. For a binary event frequency, it can show how compatible a range of underlying event frequencies is with the observed data. A narrow interval indicates greater precision than a wide interval, but does not remove limitations in the design, endpoint definition, or representativeness of the participants. The registry record does not report a confidence interval for the primary endpoint, nor does it report the estimate that such an interval would accompany.

What does the sequential design imply?

In general, sequential dose escalation allows study groups to be enrolled as dose or schedule decisions proceed. This is useful for dose-finding questions, but treatment groups do not automatically have the comparability created by random assignment. Groups may differ in dose, schedule, treatment combination, study part, or the participants enrolled. Consequently, group-level event counts should not be interpreted as if they came from a controlled head-to-head comparison. The registry record does not describe a statistical adjustment intended to make these groups comparable.

The study also lists pharmacokinetic outcomes such as maximum plasma concentration, time to maximum concentration, exposure over time, apparent clearance, apparent volume of distribution, and terminal half-life. In general, these measures characterize drug exposure and disposition. They do not directly measure a clinical outcome, and they do not establish a causal treatment effect. The record lists these outcomes but the registry entries available do not include their numerical results.

How should planning estimates be read?

In general, a sample-size planning illustration based on an observed effect asks how much information a future study might need to detect an effect under stated assumptions. It is a planning calculation, not an estimate of the probability that the completed study detected an effect. It is not “observed power.” The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such an illustration does not replace a protocol-based sample-size justification. The registry record does not report the trial’s own sample-size justification.

For this study, the nonrandomized, sequential structure is important when interpreting any planning illustration based on an observed contrast. An observed difference between groups may reflect factors other than treatment, and a calculated sample size cannot correct that limitation. The record does not report an inferential analysis for the primary endpoint, and the registry entries do not give numerical planning outputs to interpret. These general principles therefore explain how to read such methods, rather than supplying a conclusion about the trial’s result.

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-06873600 1 mg Twice a Day (BID)", "Part 1A PF-06873600 2 mg BID", "Part 1A PF-06873600 5 mg BID", "Part 1A PF-06873600 10 mg BID", "Part 1A PF-06873600 25 mg BID", "Part 1A PF-06873600 25 mg BID Biomarker")
n      <- c(1, 2, 2, 3, 9, 6)
events <- c(0, 0, 0, 0, 0, 0)
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-06873600 1 mg Twice a Day (BID)  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Part 1A PF-06873600 2 mg BID  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Part 1A PF-06873600 5 mg BID  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Part 1A PF-06873600 10 mg BID  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Part 1A PF-06873600 25 mg BID  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Part 1A PF-06873600 25 mg BID Biomarker  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The record lists many outcomes, including the primary DLT endpoint and pharmacokinetic measures. When a study examines multiple endpoints, doses, groups, or time points, the chance of at least one apparently notable finding can increase. In general, multiplicity methods can define which comparisons are confirmatory and whether error rates are adjusted. The registry record does not report a multiplicity strategy or identify a family of confirmatory comparisons. It also lists zero analyses, so there are no reported inferential results from which to assess how multiple testing was handled.

Missing-data handling is not reported in the registry record. For a participant-level safety endpoint, readers would ideally know whether endpoint status was available for all participants in the stated analysis population, how incomplete first-cycle observation was handled, and whether any participants were excluded for missing assessments. The record defines an evaluable population but does not give the number analyzed, missing endpoint information, or the handling rules for incomplete observations. It is therefore not possible to assess the influence of missing data on the primary endpoint.

The primary analysis population is described as enrolled participants who received at least one dose and had no major treatment deviations during the first cycle. This differs from an analysis of all enrolled participants and is tied to dose-finding evaluability. The number who met this definition, the number excluded, and the reasons for exclusion are not reported in the registry record. The safety group counts do not establish the primary analysis population because their definitions and follow-up may differ.

These omissions limit assessment of statistical robustness, but they do not establish that a particular method was or was not used outside the registry record. Protocol details, analysis plans, and additional results are not reported in the registry record details available for this analysis.

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: intestinal obstruction (50.0%), febrile neutropenia (30.0%), abdominal pain (30.0%), pneumonia (25.0%), stomatitis (16.7%).

The serious adverse-event information is organized by study group and includes participants at risk, participants affected, other adverse events, and deaths. These counts are descriptive. Groups differ in dose, schedule, treatment combination, and study part, and allocation was nonrandomized, so the counts do not establish that one treatment caused more or fewer serious events than another.

The listed serious-event terms include intestinal obstruction at 50.0%, febrile neutropenia at 30.0%, abdominal pain at 30.0%, pneumonia at 25.0%, stomatitis at 16.7%, and hyperbilirubinaemia at 16.7%. The registry information available does not identify the denominator or calculation basis for these term percentages. They should not be treated as percentages of all enrolled participants or compared across terms without that context.

Serious adverse events are not interchangeable with dose-limiting toxicities. The primary endpoint applies its own event definition, attribution requirements, and Cycle 1 window. Serious-event reporting may cover a broader period or category; the registry entries do not establish that every serious event met the DLT criteria. Likewise, the deaths recorded by group should not be assumed to be treatment-related because attribution is not reported.

For interpretation, the group counts describe what was recorded in each group, not a randomized comparison of safety. The registry record does not report a statistical comparison, an adjusted analysis, or uncertainty estimates for these safety figures.

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

The registry record establishes that this was a nonrandomized phase 1/2a dose-escalation and expansion study of PF-06873600, alone and with endocrine therapy. It defines a primary safety endpoint focused on dose-limiting toxicities during the first treatment cycle and describes a population considered evaluable for maximum tolerated dose. The study also included pharmacokinetic outcomes and addressed anti-tumor activity in its broader description.

What the record does not establish is the observed primary endpoint result. The DLT count and the number analyzed are not reported in the registry record. There is therefore no basis for stating how often DLTs occurred, how precise an estimate would be, or what dose was selected as the maximum tolerated dose. The absence of a reported result is not evidence that no DLTs occurred.

The study’s structure also limits what can be inferred from between-group differences. Participants were not randomized, the study proceeded sequentially, and groups differed in doses, schedules, and use of endocrine therapy. Counts from these groups cannot by themselves show that one regimen caused a difference in safety or clinical outcome. A causal comparison would require a design and analysis that address these differences; such a comparison is not reported in the registry record.

Similarly, the study’s mention of anti-tumor activity does not establish efficacy. The registry entries contain no tumor-response estimate or comparative efficacy analysis. Pharmacokinetic outcomes, which concern drug concentrations and exposure, answer a different question from whether a treatment improves health outcomes.

The status of terminated is a registry status, not an explanation of why the study stopped or a result about the intervention. The reason for termination is not reported in the registry record. Overall, the available record supports a description of the intended early-phase questions and study structure. It does not support a claim that PF-06873600 is effective, ineffective, safe, or unsafe.

14. Why This Trial Matters Statistically

Early-phase studies often need to characterize tolerability and drug exposure before a larger comparative study can be designed. This study’s primary endpoint reflects that role: it focuses on dose-limiting toxicity during a defined first-cycle window, while the secondary outcomes include pharmacokinetic measures. Separating these questions is statistically important. A safety count, a concentration measure, and a tumor-response outcome are different quantities and cannot substitute for one another.

The registry record also illustrates why study design must guide interpretation. Sequential, nonrandomized groups can be appropriate to a dose-finding objective, but they do not provide the same basis for treatment comparisons as randomized allocation. Group differences may arise from the dose or schedule, from combination treatment, from study-part differences, or from participant characteristics. Descriptive counts are useful for describing observed experience, but they do not isolate a causal effect.

Endpoint and population definitions are equally important. The primary DLT analysis population excludes participants who did not meet the stated evaluability conditions, so enrollment is not automatically the endpoint denominator. Without the analyzed count, endpoint result, and information about exclusions, readers cannot judge the event frequency or its precision. Clear reporting of those elements is necessary to connect a trial question with an interpretable estimate.

Finally, registry status and outcome reporting should be read separately. The study is listed as terminated, but the reason is not reported. That status alone does not resolve the safety or efficacy questions. The statistical lesson is to distinguish what a study was designed to examine, what data are reported, and what conclusions its design can support. For this record, the design and endpoint are described, while the primary outcome result is not reported in the registry 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.

The main limitation for interpreting the primary endpoint is that its observed count and analysis denominator are not reported in the registry record. The analysis population is defined, but the number meeting that definition is not available in the registry record. Without both the numerator and denominator, readers cannot assess the observed DLT frequency or its precision.

The nonrandomized, sequential design limits direct comparisons among groups. The listed groups differ by dose, schedule, combination treatment, and study part. There is no like-for-like randomized control comparison, and the registry record does not report a statistical adjustment that would address those differences. Any comparison of group counts would therefore be descriptive and potentially confounded.

The primary endpoint has a defined first-cycle period and event criteria, but the available record does not provide participant-level detail or explain how incomplete observation was handled. Missing-data procedures, reasons for exclusion from the primary analysis, and the number of participants with incomplete endpoint information are not reported in the registry record. The serious adverse-event summaries cannot be assumed to reproduce the primary DLT endpoint because they need not use the same event definition or time window.

The registry lists a range of outcomes and study parts, but a multiplicity strategy is not reported. Inferential analyses are also not listed. The registry entries available do not include numerical results for the primary endpoint, pharmacokinetic outcomes, or anti-tumor activity. This prevents assessment of estimates and their uncertainty.

The study is listed as terminated, but the reason for termination is not reported in the registry record. The record also does not provide the trial’s sample-size justification. These limitations constrain interpretation of the posted information; they do not establish why the study ended or what its unreported results would show.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of PF-06873600 in People With Cancer — NCT03519178.
• Registry record last updated 2025-11-14; status last verified 2025-10.
• Results first posted 2024-07-31.
• 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

This Pfizer-sponsored phase 1/2a study evaluated PF-06873600 as a single agent and in combination with endocrine therapy in people with several cancer types. The design was nonrandomized, unmasked, and sequential, with dose-escalation and expansion groups. The registry lists enrollment of 155, a start date of 2018-03-07, a primary completion date of 2023-04-05, and status terminated.

The primary endpoint was the number of participants with dose-limiting toxicities during Cycle 1, within 28 days after the first dose. The primary population was restricted to enrolled participants who received at least one dose and had no major treatment deviations during that cycle. The number analyzed and the primary endpoint result are not reported in the registry record. The reason for termination is also not reported. Accordingly, the record describes the study question and design but does not support a conclusion about the observed primary outcome or comparative treatment effects.