Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. (NCT04171141), a non-randomized phase 1 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs) Assessed Through Cycle 1.

2. Clinical Question

The study asked whether PF-07062119 could be evaluated for safety and tolerability, as a single agent and in combinations, in patients with selected advanced gastrointestinal tumors. Its registered primary endpoint counted participants with dose-limiting toxicities during Cycle 1. The registry also describes pharmacokinetic outcomes and anti-tumor activity as study aims, but the result of the primary endpoint is not reported in the registry record.

This is a safety-focused, early-phase question rather than a confirmatory comparison of treatments. Dose escalation and expansion are distinct study components, and the different arms involve different doses, combinations, or tumor types. Consequently, differences between arm-level observations would not by themselves establish that one regimen caused more or fewer toxicities than another. The registry record does not report a primary endpoint count, an estimate of anti-tumor activity, or comparative treatment effects.

3. Trial Design

This was a phase 1, open-label, non-randomized, sequential dose escalation and expansion study sponsored by Pfizer. The registry lists enrollment of 79 participants. The study began on 2019-11-19, its primary completion date is listed as 2023-11-28, and its status is terminated. The reason for termination is not reported in the registry record.

The study included a single-agent dose escalation component, dose-finding components combining PF-07062119 with anti-PD-1 or anti-VEGF treatment, and dose expansion arms. Expansion included a single-agent colorectal cancer arm, combination arms in colorectal cancer, and an arm using either combination in various tumor types. Specific arm descriptions also list dose levels and, for combination arms, dosing schedules. These groups reflect different treatment strategies and populations rather than randomized alternatives assigned under a common comparison.

Open-label means masking was not used. Sequential allocation and the absence of randomization limit the interpretation of between-arm contrasts: treatment assignment was not randomized, and the groups are not established as comparable. The registry does not report a concurrent control arm. It also does not report the protocol rationale for the dose sequence, the rules used to move between doses, or any sample-size justification.

The primary endpoint was the number of participants with dose-limiting toxicities assessed through Cycle 1, with a 28-day timeframe. Secondary outcomes include pharmacokinetic measures in Cycle 1 and Cycle 4, including maximum concentration, time to maximum concentration, and area-under-the-concentration-time-profile measures in priming and non-priming cohorts. The registry lists 20 outcome measures but no analysis records. Results for the primary endpoint and the listed pharmacokinetic outcomes 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 16 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis population included all enrolled participants who had at least 1 dose of study intervention and either experienced DLT or did not have major treatment deviations during the DLT observation period.

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 randomized study medication and had a baseline and at least 1 post-baseline measurement (after taking randomization study medication).

Only the first 6 of 17 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs) Assessed Through Cycle 1, measured over 28 Days.

The primary endpoint counts participants who experienced a dose-limiting toxicity, or DLT, during the first treatment cycle. Its timeframe is 28 days. A count of affected participants is a safety outcome: it describes how many people in the analysis population met the registered DLT criteria during the specified observation period. The registry does not report the observed count.

The record defines hematological and non-hematological events that could qualify. Examples include specified levels and durations of neutropenia, thrombocytopenia, anemia, fatigue, liver enzyme abnormalities, vomiting or diarrhea, cytokine release syndrome, and QTcF prolongation. It also includes death not clearly due to underlying disease or extraneous causes. Clinically important or persistent toxicities were to be reviewed by investigators and the sponsor. These criteria make explicit which events could count toward the endpoint; they do not imply that any particular event occurred.

In general, early-phase dose-escalation studies use DLT monitoring to characterize tolerability during a defined initial exposure period and inform decisions about further dose evaluation. That general purpose does not establish what dose decisions were made in this study. The registry record does not report the decision rules or a selected dose.

The specified analysis population includes enrolled participants who received at least one dose of study intervention and either experienced a DLT or had no major treatment deviations during the DLT observation period. The number meeting that population definition is not reported in the registry record. A count without the corresponding analysis denominator would be difficult to interpret, and neither the count nor the denominator is available as a primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be described from the registry are limited. The study is identified as phase 1, non-randomized, open-label, and sequential, with dose escalation and expansion. The primary endpoint is a participant count over a 28-day period. The registry does not report the statistical analysis plan, so the following statistical concepts are general explanations rather than claims about methods used in this study.

What does a participant count represent?

A count records the number of participants meeting an event definition. Counts are most interpretable alongside a denominator: the number of people who were eligible for that endpoint and observed during its defined period. A count alone does not describe the frequency of events unless the relevant denominator is also known. For this endpoint, the registry defines an analysis population, but does not report its size or the observed DLT count.

A count also depends on how the event is defined and assessed. The DLT description specifies event types, grades, durations, and clinical review for certain events. These details help determine what qualifies as a DLT. They do not tell the reader how many events qualified in practice. Nor does the endpoint count communicate timing or severity beyond the classifications in the definition, unless those are reported separately.

What does the 28-day timeframe mean?

A fixed observation window makes the endpoint specific to events assessed within that period. It does not describe all later safety experience. In general, participants who do not complete the observation window can create a missing-outcome problem: their status may not be fully known for the intended period. The registry does not report how incomplete observation, treatment interruptions, or missing DLT assessments were handled.

Why does the design matter?

Randomization is a method for forming groups that are comparable, on average, with respect to measured and unmeasured baseline characteristics. This study was not randomized. Its arms were organized by dose, combination, and expansion group, and the record describes them as sequential. In general, comparisons across non-randomized groups can be affected by differences in who entered each group, when they entered, and which treatment they received. An arm contrast should not be interpreted as a causal treatment effect without a suitable design and analysis supporting that conclusion.

Open-label means participants and study personnel were not masked to treatment assignment. In general, lack of masking can influence subjective assessments or reporting, although its relevance depends on the outcome and assessment procedures. The primary endpoint includes defined clinical events and investigator and sponsor review of certain toxicities. The record does not explain how assessment consistency was maintained or whether independent adjudication was used.

What can a confidence interval tell a reader?

In general, a confidence interval expresses uncertainty around an estimate under a particular statistical method. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. An interval does not correct for selection bias, confounding, missing observations, or a non-randomized design. The registry record does not report a confidence interval for the primary endpoint, and no numerical estimate is available to place within one.

How should the sample-size illustration be read?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its target effect is a stated fraction of the observed effect. In general, such an illustration asks how many participants per arm might be needed under its assumptions to detect a specified effect. It is not the study's sample-size justification and is not observed power. The illustration does not make this non-randomized trial a randomized two-arm comparison; the record specifically cautions that the arms are not a like-for-like control comparison. The actual illustration values and observed effect are not reported in the registry record, so no numerical planning result can be interpreted.

For binary outcomes, the normal approximation is a simplified way to approximate uncertainty or plan sample size. In general, its accuracy can depend on the amount of information in the data and the event frequency. The record does not identify a trial-specific method for estimating the primary endpoint or explain whether an alternative method was considered. It also does not report model assumptions, covariate adjustment, or sensitivity analyses.

What do pharmacokinetic outcomes add?

Pharmacokinetic measures describe drug concentration over time. Maximum concentration refers to the highest measured concentration in a specified profile; time to maximum concentration describes when that maximum is reached; area under a concentration-time profile summarizes exposure over a specified interval. The registry lists these measures for Cycle 1 and Cycle 4 and distinguishes priming from non-priming cohorts. These are distinct outcomes from DLT counts. Their listings do not provide actual concentration estimates, variability, or comparisons, which are not reported in the registry record.

More broadly, a statistical method cannot be reconstructed from an outcome label alone. The registry record does not report how continuous pharmacokinetic data were summarized, how missing measurements were handled, or whether analyses were adjusted. It lists no analysis records. Interpretation should therefore stay with the design, endpoint definitions, and safety counts that are explicitly recorded, while treating unreported analyses and results as unknown.

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-07062119 45 µg", "Part 1A PF-07062119 135 µg", "Part 1A PF-07062119 400 µg", "Part 1A PF-07062119 800 µg", "Part 1A PF-07062119 1600 µg", "Part 1A PF-07062119 400 µg/800 µg")
n      <- c(2, 3, 5, 9, 2, 6)
events <- c(0, 0, 0, 2, 2, 1)
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-07062119 45 µg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Part 1A PF-07062119 135 µg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Part 1A PF-07062119 400 µg  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Part 1A PF-07062119 800 µg  9  2  22.2  2.8  60.0  6.3  54.7  6.7  55.6
ARM  Part 1A PF-07062119 1600 µg  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Part 1A PF-07062119 400 µg/800 µg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 20 outcome measures, including the primary DLT outcome and multiple pharmacokinetic outcomes. It does not report a multiplicity strategy. In general, when several outcomes or comparisons are examined, the chance of finding at least one apparently unusual result can increase. Methods to address multiplicity may be prespecified, but no such procedure is described in the registry record. There are no analysis records listed, and the record does not state which outcomes were formally analyzed or how results were prioritized beyond identifying the primary endpoint.

Missing-data handling is also not reported in the registry record. The primary analysis population is defined by receipt of at least one dose plus either experiencing a DLT or having no major treatment deviations during the DLT observation period. The record does not give the number in this population, describe participants excluded from it, or explain how incomplete DLT observation was treated. It does not report rules for missing pharmacokinetic samples or other outcome measurements.

In general, missingness can matter when participants with unobserved outcomes differ systematically from those with observed outcomes. Different assumptions about those unobserved results can affect estimates. No imputation method, sensitivity analysis, or missingness summary is described in the record, so the impact of missing data cannot be assessed from the available information.

The record also does not report an analysis plan, interim analyses, or a sample-size justification. These should not be inferred from the sequential dose-escalation design. The planning illustration described in the record is not evidence of a prespecified design calculation for this trial. Because the primary result and analysis denominator are not reported, the precision and completeness of the primary endpoint analysis cannot be evaluated.

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: colitis (50.0%), small intestinal haemorrhage (33.3%), urinary tract obstruction (33.3%), diarrhoea (25.0%), impaired gastric emptying (25.0%).

The registry’s safety listing gives an overall at-risk total of 79 participants. It reports 30 participants with serious adverse events, 78 with other adverse events, and 44 deaths. These are participant counts in the safety listing and should be kept distinct from the primary endpoint, which counts participants with DLTs through Cycle 1 among a specifically defined analysis population. The DLT result is not reported in the registry record.

The arm-level entries describe groups with different dose levels or combinations. Because the study was non-randomized and the arms are not a like-for-like control comparison, their counts should not be read as comparative estimates of treatment effects. Small group sizes and differing regimens also mean that arm-level counts alone cannot establish why events occurred.

The registry lists serious adverse event terms including colitis at 50.0%, small intestinal haemorrhage at 33.3%, urinary tract obstruction at 33.3%, diarrhoea at 25.0%, impaired gastric emptying at 25.0%, and obstruction gastric at 25.0%. The denominator and counting basis for these listed percentages are not reported in the registry record. These terms do not establish that an event was caused by study treatment.

The 44 deaths are reported as a safety count; the record does not attribute them to treatment or provide causes. The primary DLT definition excludes deaths not clearly due to underlying disease or extraneous causes, but the registry does not identify which deaths, if any, met DLT criteria.

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

The study record documents an early-phase evaluation of PF-07062119 as a single agent and in combinations, with dose escalation and expansion in selected advanced gastrointestinal tumors. It specifies a safety-focused primary endpoint and lists pharmacokinetic outcomes. The safety listing includes participant counts for serious adverse events, other adverse events, and deaths. These are descriptive details about what the registry records.

The record does not report the primary DLT count, the size of the primary analysis population, or numerical results for the pharmacokinetic outcomes. It therefore does not permit an assessment of the observed DLT count against its denominator, the precision of that outcome, or the concentration profiles. Although anti-tumor activity is part of the study's stated aims, no anti-tumor result is reported in the record. No conclusions about efficacy or comparative benefit can be drawn from the information reported.

The safety counts do not show whether events were caused by PF-07062119 or a combination treatment. The recorded deaths cannot be interpreted as treatment-related on the basis of the registry information. Likewise, the listed serious adverse event terms and percentages lack a reported denominator and do not establish causality. DLTs and serious adverse events are not interchangeable categories: the primary endpoint has its own event criteria, time window, and analysis population.

The design also limits comparative interpretation. There was no randomization, masking was absent, and the groups reflect different doses, combinations, and tumor populations. General statistical reasoning cautions that comparisons among such groups may be confounded and do not automatically estimate causal treatment effects. The record does not report adjusted analyses or a control group that would address this limitation.

Accordingly, the record supports describing study structure, endpoint definitions, and reported safety counts, but not estimating treatment effects or drawing conclusions about the primary endpoint. Missing results should be treated as unknown rather than as evidence that an event did or did not occur.

14. Why This Trial Matters Statistically

This trial illustrates why early-phase design and statistical interpretation need to be read together. The study combined sequential dose escalation with dose-finding and expansion groups, while evaluating a single agent and combinations. Those components address different questions and do not create randomized comparisons. Recognizing the design prevents descriptive differences between arms from being mistaken for causal effects.

The primary endpoint is a count over a defined observation period, with detailed criteria for qualifying toxicities. That specificity is important: a safety outcome depends on who is included, which events qualify, and when events are assessed. Here, the registry defines the analysis population and the DLT criteria, but does not report the primary count or population size. The distinction between a defined method and an available result is central to interpreting registry entries.

The safety listing also shows why outcome categories should not be collapsed. Serious adverse events, other adverse events, deaths, and DLTs have different meanings and may use different populations or time windows. A count in one category cannot be substituted for a missing result in another. Nor does an event count establish causation.

Finally, the record demonstrates the boundary between a planning illustration and a trial's actual design. A calculation based on an observed effect and stated assumptions is not a report of observed power, nor does it explain how enrollment was originally chosen. The registry does not report the trial's own sample-size justification or statistical analysis plan. For readers, these absences matter: they constrain assessment of precision, missing data, multiplicity, and the intended interpretation of 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.

The main limitation for statistical interpretation is that the registry record does not report the primary endpoint result or its analysis denominator. It defines the population and DLT criteria, but without the count and denominator, the primary safety outcome cannot be quantified. The registry lists 79 enrolled participants, but that number does not establish how many met the primary analysis-population definition.

The study was non-randomized, open-label, and sequential, with arms involving different doses, combinations, and tumor groups. There is no randomized control comparison. Arm-level event counts are therefore descriptive and should not be interpreted as causal differences between regimens. The reason for the terminated status is not reported in the registry record.

The safety information includes overall and arm-level counts, but the record does not report attribution of events to treatment. The denominators and counting basis for the percentages attached to listed serious adverse event terms are not reported in the registry record. The deaths are not assigned causes or treatment relationships in the information described.

The registry lists 20 outcome measures and no analysis records. It does not report numerical results for the primary endpoint or pharmacokinetic outcomes, an analysis plan, multiplicity handling, missing-data methods, interim analyses, or a sample-size justification. It also does not report the number of participants with complete endpoint observation or any sensitivity analysis. These omissions prevent assessment of precision, robustness, or the consequences of incomplete follow-up. They do not show that analyses were or were not conducted outside the registry record; their status is not reported there.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Test the Safety and Tolerability of PF-07062119 in Patients With Selected Advanced or Metastatic Gastrointestinal Tumors. — NCT04171141.
• Registry record last updated 2025-01-16; status last verified 2025-01.
• Results first posted 2025-01-16.
• 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

NCT04171141 is a phase 1, open-label, non-randomized, sequential dose escalation and expansion study sponsored by Pfizer. It enrolled 79 participants with selected advanced or metastatic gastrointestinal tumors and evaluated PF-07062119 alone and with anti-PD-1 or anti-VEGF treatment. The registry lists the study as terminated and gives a primary completion date of 2023-11-28.

The primary endpoint counts participants with DLTs through Cycle 1, over 28 days. Its criteria and analysis-population definition are recorded, but the endpoint result and analysis population size are not reported in the registry record. The safety listing reports 30 participants with serious adverse events, 78 with other adverse events, and 44 deaths. The record lists pharmacokinetic outcomes but does not report their numerical results. No analysis records are listed. Because there was no randomization, arm-level observations are not a like-for-like control comparison.