A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors (NCT02129205), a registered phase 1 study. The primary outcome is Number of Participants With Dose-limiting Toxicities (DLT) (Part 1).

2. Clinical Question

3. Trial Design

This was a Phase 1, open-label dose-escalation study of PF-06650808 in patients with advanced solid tumors. The registry lists masking as none. The recorded enrollment was 40, and the study status is terminated. The registry gives a start date of 2014-06 and a primary completion date of 2017-07. It identifies Pfizer as the sponsor.

The intervention is listed as PF-06650808, with dose groups from 0.2 mg/kg through 4.68 mg/kg. The registry record does not give arm descriptions. It does not state how participants were assigned to dose levels or provide details of the escalation rules, cohort decisions, or stopping criteria. These design details are not reported in the registry record and should not be inferred from the sequence of listed doses.

The primary endpoint applies to Part 1 and counts participants with dose-limiting toxicities during Day 1 up to Day 21. The record also lists outcomes in Part 1 and Part 2 covering treatment-emergent adverse events, laboratory abnormalities, vital signs, and pharmacokinetic measures. The presence of outcomes for both parts does not supply the results for either part.

The study was not described as randomized, and allocation is not stated. The registry specifically cautions that its arms are not a like-for-like control comparison. Thus, the dose groups are best understood as part of an escalation study, not as randomized treatment groups for estimating a causal contrast. The protocol’s planned sample-size justification, detailed statistical plan, and any interim analysis procedures are not reported 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.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set was used, which included all enrolled participants who received at least one dose of study medication.

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 participants who received at least 1 dose of study treatment.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose-limiting Toxicities (DLT) (Part 1), measured over Day 1 up to Day 21.

The primary endpoint is the number of participants with dose-limiting toxicities in Part 1 during Day 1 up to Day 21. It is a count of participants, not a measure of tumor response or a comparison of treatment efficacy. The registry says that adverse-event severity was graded using CTCAE version 4.03.

The listed DLT criteria cover specified hematologic and non-hematologic toxicities in the first treatment cycle, which is described as 21 days. Examples include Grade 4 neutropenia lasting more than 7 days, febrile neutropenia, and Grade 3 or higher neutropenia with infection. The criteria also include specified thrombocytopenia and non-hematologic toxicities, as well as clinically important or persistent toxicities that could be considered DLTs after Sponsor and investigator review. Events attributable to disease progression were excluded under the stated definition.

In general, a DLT endpoint is used in dose escalation to identify toxicity considered sufficiently important to inform decisions about further dose increases and later dose selection. It focuses attention on a defined early treatment period and prespecified toxicity criteria. The registry’s description explains the endpoint’s intended role, but does not report how many participants met the definition, the dose-level decisions, or the resulting maximum tolerated or recommended Phase 2 dose.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a count of participants who experienced at least one event meeting the DLT definition. For each dose group, the relevant descriptive quantity would ordinarily be the number meeting the definition and the number assessed. The registry describes the endpoint and its population but does not report the DLT counts or group-specific analysis. It is therefore not possible to interpret a primary endpoint rate from the registry record.

What does a count measure?

A participant count records how many people met an outcome definition; it is not the same as a count of all events. A participant with more than one qualifying event would still contribute as a participant with a DLT if the outcome is defined as the number of participants. Counts are often accompanied by denominators so readers can understand how many participants were observed. In this record, the primary endpoint denominator is described through the safety analysis set, which includes enrolled participants who received at least one dose, but the size of that set and the DLT numerator are not reported.

In general, a proportion is a count divided by its relevant denominator. Its uncertainty depends in part on the amount of information available; estimates from small groups are typically less precise than estimates from larger groups. A confidence interval, when reported, gives a range of values compatible with the data under the specified statistical method. No confidence interval for the DLT endpoint is reported in the registry record. The serious-event summaries give group sizes and affected counts, but do not provide confidence intervals in the posted results.

Why does the dose-escalation context matter?

In general, a dose-escalation study examines safety as dose levels increase, with the purpose of informing later dose selection. This differs from a randomized comparison in which participants are assigned to treatment groups under a common comparison design. Here, allocation is not stated, masking is none, and the registry explicitly says the arms are not a like-for-like control comparison. Consequently, a numerical difference in adverse-event counts across dose levels should not automatically be interpreted as a causal effect of dose. The registry does not report the dose-escalation algorithm, decision rules, or statistical model, so the method used to make dose decisions cannot be described.

How should the planning illustration be read?

The planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect defined as a stated fraction of the observed effect. These assumptions describe an illustrative calculation, not the original trial design. The illustration is not observed power, and its sample-size values are planning quantities rather than observed trial findings. The registry record does not report the protocol’s sample-size justification or establish that the illustration’s assumptions were used in planning or conduct.

In general, a sample-size calculation depends on the outcome, the effect targeted for detection, the variability or event frequency assumed, the allocation design, and the desired operating characteristics. When planning is based on an observed effect, the resulting estimate can be sensitive to uncertainty in that effect, especially when the underlying groups are small. A fraction of an observed effect is a hypothetical planning target, not a new clinical result. The normal approximation is a modeling assumption; how suitable it is depends on the particular outcome and data. The record does not report enough detail to assess the exact calculation beyond the stated assumptions.

What does over-dispersion mean in general?

For count data, over-dispersion means that the observed variability is greater than a model assumes. If unrecognized, standard errors can be too small and uncertainty can appear narrower than warranted. This is a general statistical concern, not a finding about this study: the registry does not report a model for the primary endpoint, a dispersion estimate, or a diagnostic assessment. The endpoint itself is a participant count with a binary event status, and the registry record contains no inferential analysis with which to evaluate model fit.

The record lists 15 outcome measures, including adverse events, laboratory abnormalities, vital signs, and pharmacokinetic measures such as Cmax, Tmax, and AUCtau. In general, examining many outcomes can raise multiplicity questions: the chance of at least one apparently unusual result can increase when many tests are performed. The registry does not report whether formal tests were conducted, what hypotheses were prespecified for secondary outcomes, or whether any multiplicity adjustment was planned. These omissions limit interpretation of any isolated statistical finding, although no such test results are posted for the primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures. The primary outcome is the number of participants with DLTs in Part 1; secondary measures include treatment-emergent adverse events, laboratory abnormalities, vital signs, and pharmacokinetic measures in Part 1 and Part 2. The number of analyses recorded is 0. No inferential results for the primary endpoint are reported.

When a study assesses multiple outcomes or conducts multiple statistical tests, multiplicity can affect how isolated findings should be interpreted. In general, a multiplicity plan specifies which outcomes are confirmatory and whether or how error rates are controlled across tests. The registry record does not report such a plan, any adjustment method, or the role of the secondary outcomes in formal hypothesis testing. It is therefore not possible to determine how multiplicity was handled.

The primary endpoint uses the safety analysis set, defined as enrolled participants who received at least one dose of study medication. The number included in that set is not reported. The record does not state how missing or incomplete endpoint data were handled, whether participants with incomplete observation were excluded, or whether any imputation was used. Missing-data methods are not reported in the registry record.

The enrollment figure is 40, but the safety analysis population is defined by treatment receipt and its size is not given. Enrollment should not be assumed to equal the analysis population. The registry does not report participant flow by dose group, the number assessed for DLT, or the completeness of follow-up within the stated endpoint period. These gaps make it difficult to assess whether the posted safety summaries include all enrolled participants or how missing observations might affect interpretation.

11. 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: neutropenia (100.0%), abdominal pain (50.0%), enterocolitis (50.0%), mucosal inflammation (50.0%), rash macular (50.0%).

The serious adverse-event summaries report the number affected and the number at risk in each dose group. The figures are 0 of 2 at 0.2 mg/kg, 0 of 2 at 0.4 mg/kg, 0 of 2 at 0.8 mg/kg, and 0 of 2 at 1.6 mg/kg; 1 of 7 at 2.0 mg/kg; 3 of 11 at 2.4 mg/kg; 3 of 6 at 3.0 mg/kg; 3 of 6 at 3.6 mg/kg; and 2 of 2 at 4.68 mg/kg. The record lists 1 death in the 2.0 mg/kg group and 1 in the 2.4 mg/kg group, and 0 deaths in the other listed groups.

These are descriptive counts. They do not identify whether a serious event or death was caused by study medication, and the registry summary does not provide event timing, duration, outcome, or participant-level detail. The serious-event terms are listed with percentages, including neutropenia at 100.0%; the summary does not clarify the denominator for those percentages. They should not be treated as dose-specific risks or compared with the affected-participant counts without that context.

In general, small group sizes make percentages unstable: a change in the status of a participant can materially alter a group summary. Zero recorded serious events in a group is not proof of zero underlying risk. These summaries describe what was recorded in the registry and do not establish comparative safety between dose levels.

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

The record establishes that NCT02129205 was a Phase 1 dose-escalation study of PF-06650808 in patients with advanced solid tumors, with a stated focus on safety and tolerability. It defines a primary DLT endpoint for Part 1 and lists a safety analysis population. It also reports serious adverse-event counts by dose group and a small number of deaths in the group summaries. These details describe the study’s focus and the posted safety summaries.

The primary endpoint result is not reported in the registry record. There is no posted DLT count, no DLT estimate by dose, and no reported decision identifying a maximum tolerated dose or recommended Phase 2 dose. Therefore, the study’s stated objectives should not be mistaken for reported findings. The record also contains no analysis records, confidence intervals, or inferential tests for the primary endpoint.

The adverse-event counts do not establish causation. The study has no described randomized control group, allocation is not stated, and the registry warns that the arms are not a like-for-like comparison. The varying group sizes and the dose-escalation setting also mean that differences between groups cannot be read as though participants had been randomly assigned to otherwise comparable groups. Counts by themselves do not show whether a dose caused an event or whether one dose has a different underlying risk.

In general, safety summaries can help describe what was observed in a study, but interpretation also depends on event definitions, follow-up, completeness of reporting, and the population assessed. The registry does not provide enough detail to evaluate all of those features for the primary DLT endpoint. The appropriate statistical conclusion is therefore limited: the registry records adverse-event summaries, while the primary endpoint outcome and its analysis are not reported. No conclusion about clinical benefit or lack of benefit follows from these safety counts.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a protocol question and a reported statistical result. The registry gives a clear purpose—assessing safety and tolerability across increasing doses—and defines a DLT outcome for a specific early period. Yet the primary DLT result is not reported. Knowing the endpoint definition is not enough to know the observed event count, the uncertainty around it, or how the findings influenced dose selection.

It also shows why design context matters when reading dose-group summaries. The listed groups have different sizes, allocation is not stated, and the record cautions that they are not like-for-like control groups. A count comparison across doses can be useful descriptively within an escalation study, but should not be presented as a randomized treatment contrast. Statistical interpretation must account for how participants came to receive each dose, and that process is not described in sufficient detail in the registry record.

Finally, the record highlights the value of reporting denominators, analysis populations, missing-data handling, uncertainty, and multiplicity plans. The safety analysis set is defined, but its size and the primary endpoint count are not given. The record lists multiple outcomes but does not report an analysis plan or analyses. Without those details, readers cannot assess the precision of the primary endpoint estimate or the extent to which secondary findings were exploratory. These are general reporting concerns that matter particularly when event counts and dose groups are limited.

14. 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 statistical interpretation is that the primary outcome result is absent. Although the registry defines DLTs and their observation period, it does not report the number of participants with DLTs, by dose or overall. The registry also does not report the maximum tolerated dose or recommended Phase 2 dose. Consequently, the central dose-escalation question cannot be answered from the posted primary endpoint information.

The safety summaries have small, uneven group sizes, from 2 participants in several groups to 11 participants in the 2.4 mg/kg group. Such groups provide limited precision for estimating event frequencies. The record does not report confidence intervals or a statistical comparison across dose levels. The groups are not described as randomized, and the registry explicitly cautions against treating them as like-for-like control groups.

The registry does not state the allocation process, dose-escalation rules, stopping decisions, or detailed participant flow. It does not report the safety analysis set size, endpoint-specific missing-data handling, or completeness of observation. The denominator for the listed serious adverse-event term percentages is not clarified in the summary. These omissions make it harder to reconstruct how the reported safety summaries relate to the full enrolled population.

Finally, no statistical analysis plan, multiplicity approach, or interim analysis procedure is reported. The registry lists several outcome types, but does not provide primary endpoint analyses or inferential results. The study status is terminated; the reason for termination is not reported in the registry record. These limitations concern what can be concluded from the registry record and do not, by themselves, explain why the study ended or establish that any individual event was caused by treatment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors — NCT02129205.
• Registry record last updated 2019-03-29; status last verified 2018-12.
• Results first posted 2019-03-29.
• 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.

18. Record Summary

NCT02129205 was a Phase 1 dose-escalation study of PF-06650808 in patients with advanced solid tumors, sponsored by Pfizer. The registry lists enrollment of 40, a start date of 2014-06, primary completion in 2017-07, and status as terminated. Masking is listed as none.

The primary endpoint was the number of participants with DLTs in Part 1 during Day 1 up to Day 21, assessed in the safety analysis set of enrolled participants who received at least one dose. The registry describes the DLT criteria but does not report the primary endpoint result or analysis. It does report serious adverse-event counts by dose group. Allocation, the reason for termination, the detailed statistical plan, and missing-data methods are not reported in the registry record.