Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid 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-07209960 in Advanced or Metastatic Solid Tumors (NCT04628780), a non-randomized phase 1 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

The study also assessed safety, pharmacokinetics, pharmacodynamics, and potential anti-tumor activity. Secondary outcomes included objective response under RECIST Version 1.1, disease control, time to progression, duration of response, progression-free survival, and categories of antidrug antibodies and antibodies against IL-15. The registry lists 18 outcome measures, but the detailed primary result is not reported in the registry record.

The clinical question is consequently descriptive and early phase: what safety and other study observations arose while evaluating PF-07209960 across dose levels and selected tumor cohorts? It is not a randomized comparison of PF-07209960 against another treatment or against no treatment. The registry record lists enrollment of 37, while the reported dose groups and their results must be read as study-specific observations rather than evidence of comparative benefit.

3. Trial Design

This was a Phase 1, first-in-human, open-label, multicenter, multiple-dose study of PF-07209960. The registry classifies its allocation as non-randomized and its design model as sequential. Enrollment was 37. The recorded start date was 2020-12-16, and the primary completion date was 2023-05-03. The study status is terminated.

The study had two parts. Part 1 was single-agent dose escalation, in which participants received escalating dose levels. Its stated purpose was to determine a recommended dose. Part 2 was dose expansion in selected tumor types at the recommended dose. The described expansion cohorts were non-small-cell lung cancer, renal cell carcinoma, and urothelial carcinoma. The registry also lists other conditions, including squamous cell carcinoma of the head and neck, colorectal carcinoma, and ovarian carcinoma; it does not describe expansion cohorts for each listed condition.

Open-label means the study was not masked. Non-randomized means participants were not allocated by random assignment to treatment groups. Sequential escalation also means that dose groups arise within a dose-finding structure rather than as concurrent randomized alternatives. As a result, comparisons between dose groups can reflect differences in who entered each group, when they entered, or what dose they received, as well as any relationship between dose and outcomes. The registry record does not report a control arm.

The primary endpoint was the number of participants with dose-limiting toxicities during Cycle 1, specified as 28 days. Monitoring for dose-limiting toxicities occurred during Part 1. The registry’s primary endpoint description gives criteria for being evaluable and says that participants who did not meet those criteria might be replaced. Its population description gives a separate evaluability statement, which is not worded identically.

Termination is the recorded study status; the reason for termination is not reported in the registry record. The record does not report a planned sample-size justification or explain whether termination changed the planned analyses. No randomized efficacy comparison should be inferred from this design.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 37 participants were enrolled and assigned to study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The DLT analysis set was a subset of the safety analysis set. A participant was classified as DLT-evaluable if he/she experienced a DLT or received 100% of the planned doses and had received all scheduled safety assessments during the DLT window.

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 were randomized.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

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

The primary endpoint is the number of participants with dose-limiting toxicities during Cycle 1, defined in the record as 28 days. The registry describes dose-limiting toxicities as adverse events occurring in the first treatment cycle or within 28 days after treatment began, at least possibly related to PF-07209960. Monitoring for these toxicities occurred during Part 1.

The endpoint is used in early dose escalation to characterize tolerability at the tested dose levels and inform selection of a dose for further study. It is a count of participants meeting the endpoint definition, not a measure of the total number of adverse events, their duration, or their severity beyond the criteria used to classify a toxicity as dose-limiting. The registry record does not report the number of participants meeting the endpoint in each dose group.

Eligibility for the dose-limiting toxicity analysis is described in two places. The endpoint description says a participant was evaluable if they experienced a dose-limiting toxicity or, without one, received 2 doses during Cycle 1 and completed all scheduled safety assessments during the dose-limiting toxicity window. It also says participants who failed to meet the criteria might be replaced. The population description instead says evaluability required a dose-limiting toxicity or receipt of 100% of planned doses, along with all scheduled safety assessments during the window. These statements should be read as separately recorded descriptions; the registry does not resolve their difference.

A count endpoint is useful for dose-finding because it focuses on whether participants crossed a prespecified toxicity threshold within a defined period. It does not by itself summarize all safety experience or establish a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a non-randomized, open-label, sequential Phase 1 design. The methods relevant to interpreting its results are therefore those of dose-finding and descriptive safety assessment, rather than a randomized comparison. The record does not report a full statistical analysis plan. General explanations below distinguish statistical principles from methods specifically documented for this study.

What does a count endpoint represent?

The primary outcome is the number of participants with dose-limiting toxicities in Cycle 1. A count records how many participants meet a defined endpoint; it is not the same as the number of individual toxicity events. A participant could potentially have more than one event, but the endpoint is framed as a count of participants. The registry record does not provide the observed primary endpoint count by dose group, so no endpoint rate or interval can be interpreted from this entry.

General: For a binary participant-level outcome, an event proportion is commonly estimated by dividing participants with the event by those evaluated for that outcome. The denominator matters: it should correspond to the analysis population and endpoint definition. A count without its relevant denominator does not identify the event proportion, while a proportion without a clear evaluable population can also be difficult to interpret. No calculation of this kind is appropriate when the necessary primary endpoint counts are not reported.

Why does dose escalation affect comparison?

In a randomized trial, random assignment is intended to balance prognostic factors between treatment groups on average. This study was non-randomized and sequential, so those protections do not apply. Participants at different dose levels may differ for reasons other than dose, and cohorts may have been enrolled at different points in the study. A contrast between groups would consequently be descriptive, not a randomized estimate of the effect of changing dose.

General: Dose-escalation studies use early safety observations to guide evaluation of dose levels. The interpretation depends on the endpoint definition, the observation period, the rules for evaluability, and the decision process for moving between doses. The registry record states that Part 1 aimed to determine a recommended dose and that dose-limiting toxicities were monitored there. It does not report the specific escalation algorithm, dose-selection rule, or statistical model used, so none should be assumed.

What does open-label imply?

Open-label means treatment masking was absent. For an outcome based on adverse-event classification, awareness of treatment can be relevant to assessment and reporting. The registry identifies dose-limiting toxicities as at least possibly related to PF-07209960, but does not report an independent blinded adjudication process. The record therefore does not establish whether outcome assessment was blinded or independently reviewed.

General: Masking can reduce the potential for expectations to influence assessment, especially when endpoint classification involves judgment. Its absence does not prove that assessments were biased; it means that the possibility cannot be excluded from the design description alone. Objective definitions and consistent assessment procedures can also matter, but further details are not reported in the registry record.

How should uncertainty be understood?

General: A confidence interval describes a range of values compatible with the observed data under the assumptions of the chosen statistical method. In a small early-phase study, estimates can be imprecise, and an interval can remain wide even when the observed count is available. The registry record does not report a confidence interval for the primary endpoint, and without the endpoint counts and evaluable denominators, the precision of the primary estimate cannot be assessed.

General: Statistical significance tests address a specified null hypothesis under a specified model; they do not by themselves measure clinical importance or establish causation. The registry lists 0 analyses. That registry entry does not provide a sponsor analysis or a hypothesis-testing result for the primary endpoint. The record also does not report a statistical analysis plan, planned hypothesis tests, or an adjustment strategy for multiple outcomes.

What do planning illustrations mean?

General: A sample-size illustration based on an observed effect is a planning exercise, not a description of the trial’s achieved power. The record states that its planning assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect set as a stated fraction of the observed effect. For time-to-event illustrations, it specifies total events; for other outcomes, it specifies participants per arm. Such calculations do not change the original study design or establish what the study was designed to detect.

The record explicitly characterizes these calculations as planning illustrations rather than the trial’s own design. Since the study was non-randomized and the primary result is not reported, these assumptions should not be taken as evidence that the dose-escalation study had a particular observed power. Nor should a hypothetical two-arm planning framework be confused with the actual sequential design.

What is not documented?

The registry record does not report the primary endpoint counts, the reason for termination, the sample-size justification, interim analyses, a full statistical plan, or a missing-data method. It also does not provide enough information to determine whether all enrolled participants were evaluable for each outcome. These are limits on what can be inferred from the record, not evidence that a particular method was or was not used outside the information recorded there.

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-07209960 1 mg SC", "PF-07209960 3 mg SC", "PF-07209960 10 mg SC", "PF-07209960 15 mg SC", "PF-07209960 20 mg SC", "PF-07209960 30 mg SC")
n      <- c(4, 3, 4, 2, 10, 4)
events <- c(0, 0, 0, 0, 3, 3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  PF-07209960 1 mg SC  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PF-07209960 3 mg SC  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-07209960 10 mg SC  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PF-07209960 15 mg SC  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  PF-07209960 20 mg SC  10  3  30.0  6.7  65.2  10.8  60.3  10.9  61.0
ARM  PF-07209960 30 mg SC  4  3  75.0  19.4  99.4  30.1  95.4  28.4  94.7

11. Multiplicity, Missing Data and Analysis Populations

The study lists a broad set of outcomes, including the primary dose-limiting toxicity count and secondary measures of objective response, immunogenicity, time to progression, duration of response, progression-free survival, and disease control. When multiple outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if no multiplicity strategy is used. General: multiplicity procedures can control that risk, but they require a defined family of tests and an analysis plan.

The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified approach to interpreting multiple results. It also lists 0 analyses. The record therefore does not support a claim that a particular adjustment was applied, nor does it establish how secondary findings were prioritized. The presence of many listed outcomes should encourage descriptive interpretation rather than selective emphasis on any single result.

Missing-data handling is not reported in the registry record. The endpoint description does state that participants who did not meet dose-limiting toxicity evaluability criteria might be replaced. This is a description of the evaluability and replacement approach, not a complete method for handling missing outcomes. The registry does not explain how participants with incomplete follow-up, missed assessments, or unavailable outcome measurements were treated in analyses.

Analysis populations also require care. The primary endpoint description refers to a dose-limiting toxicity analysis set that was a subset of the safety analysis set. It gives evaluability criteria involving experiencing a dose-limiting toxicity or receiving 2 doses during Cycle 1 and completing scheduled safety assessments. The population description instead refers to experiencing a dose-limiting toxicity or receiving 100% of planned doses, with scheduled assessments completed. Because the wording differs, the registry record does not make clear whether these descriptions refer to distinct operational rules or how the difference was resolved.

Accordingly, the enrolled population, safety analysis set, and dose-limiting toxicity-evaluable population should not be assumed to be identical. Outcome-specific denominators and exclusions are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cytokine release syndrome (66.7%), abdominal pain (50.0%), anaemia (33.3%), disease progression (33.3%), blood creatinine increased (33.3%).

The registry reports safety counts separately for the listed PF-07209960 dose groups. For serious adverse events, the affected counts are 3 of 4 at 1 mg SC, 3 of 4 at 3 mg SC, 1 of 4 at 10 mg SC, 1 of 3 at 15 mg SC, 13 of 16 at 20 mg SC, and 5 of 6 at 30 mg SC. For other adverse events, the affected counts are 4 of 4, 2 of 4, 3 of 4, 3 of 3, 16 of 16, and 5 of 6, respectively. The recorded death counts are 1, 1, 1, 1, 3, and 1, respectively, across those same groups.

These are descriptive counts from a non-randomized, sequential study. Dose groups are not randomized control arms, and their counts should not be used to make direct causal comparisons. The denominator listed for each group gives context for its count, but the registry does not report the primary dose-limiting toxicity results or fuller outcome-specific follow-up details in this entry.

The most frequently listed serious adverse event terms are cytokine release syndrome (66.7%), abdominal pain (50.0%), anaemia (33.3%), disease progression (33.3%), blood creatinine increased (33.3%), and rash (33.3%). The registry does not provide enough detail to determine whether a participant could contribute to multiple terms, or how these term percentages relate to the participant counts in each dose group. They should not be read as the primary endpoint or as a complete account of safety.

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

The record establishes that PF-07209960 was evaluated in a first-in-human, Phase 1, open-label study with dose escalation and dose expansion in participants with selected advanced or metastatic solid tumors. It also documents the intended use of a Cycle 1 dose-limiting toxicity count for dose escalation and provides descriptive safety counts by dose group. These registry entries characterize the study’s structure and the types of observations recorded.

The record does not report the primary endpoint counts. It therefore does not show how many participants met the dose-limiting toxicity definition in each group, how precise those estimates would be, or how the primary endpoint informed dose selection. Although the study description says Part 1 aimed to determine a recommended dose, the recommended dose itself is not identified in the registry record.

The study is not a randomized treatment comparison. Differences between its sequential dose groups cannot be interpreted as proof that a dose caused a difference in adverse events or other outcomes. The safety counts are informative as descriptions of the groups recorded, but they do not establish a comparative risk. The listed secondary outcomes similarly do not establish treatment benefit; their results and analysis details are not reported in this record.

The status is terminated, but the reason is not reported in the registry record. That status alone does not explain whether the study ended as planned, whether data collection was affected, or how the decision related to safety or other findings.

General: Early-phase studies can characterize initial safety observations and support further dose evaluation, but they are not automatically designed to provide definitive estimates of comparative efficacy. Here, conclusions should remain bounded by the posted information: the design and outcome definitions are described, and selected safety counts are recorded, while the primary result and several analysis details are absent. No conclusion that PF-07209960 works or does not work follows from this registry entry.

14. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early-phase research: dose groups are created to support sequential evaluation, not to act as interchangeable comparison arms. The record identifies a non-randomized, sequential design, so any numerical differences between dose groups are descriptive. Treating them as controlled contrasts would ignore the design and could overstate what the data establish.

The primary endpoint also shows why endpoint definitions and analysis populations matter. Dose-limiting toxicity is restricted to a specified observation window and a relationship to study treatment, while evaluability depends on treatment and safety-assessment completion. The endpoint description and population description state evaluability criteria differently. Such details affect which participants contribute to an endpoint count and therefore how a count should be interpreted.

Another statistical lesson is that a listed outcome is not the same as a reported result. The registry identifies the primary endpoint and multiple secondary outcomes, but the primary counts are not reported in the record. Without those counts and their denominators, readers cannot assess the primary endpoint’s observed frequency or precision. Registry completeness is therefore part of statistical interpretability, not merely an administrative detail.

The record also makes clear why safety counts require context. Group sizes differ, the study was not randomized, and the groups were assembled sequentially. Counts and percentages can describe observations, but they do not by themselves distinguish a dose effect from differences in participant mix, follow-up, or other factors. The posted serious adverse event terms should likewise be read as descriptive, not as a causal ranking of doses.

Finally, planning illustrations based on an observed effect should not be confused with the design of this Phase 1 study or with observed power. Keeping planning calculations separate from the actual design, endpoint results, and analysis populations helps prevent an exploratory dose-finding record from being interpreted as a confirmatory comparison.

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 counts. The primary outcome is clearly described, but its observed results and the denominators evaluated at each dose are not available in this record. Thus, the endpoint’s frequency and precision cannot be assessed from the posted information.

The study was open label, non-randomized, and sequential. There was no randomized control group, so differences among dose groups are not like-for-like comparisons. The record does not report adjustment for differences between groups or a method for controlling confounding. The design supports descriptive interpretation, not a causal estimate of dose effects.

The registry gives two differently worded descriptions of dose-limiting toxicity evaluability. One refers to receiving 2 doses during Cycle 1 if no toxicity occurred; the other refers to receiving 100% of planned doses. Both also require scheduled safety assessments. The record does not explain how these descriptions were reconciled or which rule governed the reported analysis.

The study status is terminated, but the reason is not reported in the registry record. The record also does not report a sample-size justification, a full statistical analysis plan, interim analyses, missing-data handling, or multiplicity methods. It lists 18 outcome measures and 0 analyses, which limits the available basis for interpreting endpoint-specific estimates and uncertainty.

The safety information is descriptive and does not include enough detail in this entry to establish how adverse-event terms overlap, how follow-up differed among groups, or how each outcome’s analysis population was defined. These limitations do not establish that a particular bias or problem occurred; they mark what cannot be determined from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Test the Safety and Tolerability of PF-07209960 in Advanced or Metastatic Solid Tumors — NCT04628780.
• Registry record last updated 2024-07-29; status last verified 2024-02.
• Results first posted 2024-07-29.
• 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.

19. Record Summary

NCT04628780 is a Phase 1, first-in-human, open-label, non-randomized, sequential study of PF-07209960 in advanced or metastatic solid tumors. The record describes single-agent dose escalation followed by dose expansion in selected tumor types. Enrollment was 37. The study started on 2020-12-16, reached primary completion on 2023-05-03, and is recorded as terminated.

The primary endpoint was the number of participants with dose-limiting toxicities during Cycle 1, defined as 28 days. The endpoint was intended to inform dose escalation. The registry record does not report the primary endpoint counts. It lists secondary outcomes covering response, disease control, progression, survival, and immunogenicity, as well as descriptive safety counts by dose group.

Because allocation was non-randomized and sequential, dose groups are not valid randomized controls for one another. The registry does not report the reason for termination, a sample-size justification, the full statistical plan, or missing-data and multiplicity methods. Conclusions should therefore remain descriptive and limited to the information recorded.