Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001) (NCT02720068), a non-randomized phase 1 study. The primary outcome is Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT).

2. Clinical Question

The study’s broader aims included assessing safety and pharmacokinetics and estimating a recommended Phase 2 dose for selected combinations. Part A used dose escalation, while Part B included dose confirmation and expansion cohorts. The Part B summary also describes assessment of objective response across several treatment approaches. These different aims concern dose tolerability, drug exposure, and antitumor activity; they are not interchangeable questions.

Because treatment assignment was not randomized, differences between groups cannot be interpreted as unbiased treatment effects. Groups received different regimens and were part of a dose-finding and expansion study, rather than a controlled comparison designed to isolate the effect of one treatment against another.

3. Trial Design

The registry classifies NCT02720068 as a phase 1, nonrandomized, open-label, parallel-group study. It lists enrollment as 481 and study status as completed. The recorded start date is 2016-05-02, and the primary completion date is 2024-03-15. The registry record does not report the statistical rationale for the enrollment target.

The study had two broad parts. Part A used dose escalation of favezelimab alone or with pembrolizumab, with favezelimab doses ranging from 7 mg to 700 mg. Part B used dose confirmation and expansion cohorts. Its listed regimens included favezelimab alone; combinations with pembrolizumab at different favezelimab doses; combinations with pembrolizumab and mFOLFOX7, FOLFIRI, or lenvatinib; and the coformulation MK-4280A. Most listed infusions were administered on Day 1 of each 21-day cycle. The lenvatinib regimen also specified daily oral dosing.

Part A’s dose-escalation objective differs from Part B’s dose-confirmation and expansion objectives. The brief study description says Part B aimed to estimate the recommended Phase 2 dose for selected combinations based on dose-limiting toxicity, and also to assess efficacy in expansion cohorts. It describes the possibility of an additional course for some participants with investigator-determined progressive disease after completing initial treatment.

The groups were not randomized, and masking was absent. Accordingly, regimen groups should not be read as randomized treatment and control arms. The registry record does not report a detailed allocation procedure, an analysis plan, or a sample-size justification. The variety of regimens also means that results from one group would not automatically answer questions about another regimen.

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: One participant received 2 randomization numbers due to an erroneous initial randomization, but is only counted once in Participant Flow due to the rapid correction and drug administration only happening after the correction.

Only the first 6 of 18 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received ≥1 dose of study treatment prior to determination of maximum tolerated dose, and were observed for safety for 21 days after their first dose of assigned treatment or experienced a DLT prior to 21 days after their first dose of assigned treatment.

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.

Only the first 6 of 19 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT), measured over Up to 21 days (Cycle 1).

The primary endpoint is the number of participants who experienced a dose-limiting toxicity (DLT), assessed during the first cycle, defined as 21 days. The registry record describes DLTs as specified severe or persistent toxicities, including certain severe hematologic or nonhematologic events, febrile neutropenia, treatment discontinuation due to a drug-related adverse event, a treatment-related toxicity causing a delay in starting the next cycle, or a Grade 5 toxicity. The full definition includes qualifications and exceptions.

In early-phase research, DLTs are used to evaluate whether treatment-related toxicity during an initial observation period is compatible with continuing dose development. This is a general explanation of the endpoint’s role; it does not establish what dose should be used or what the observed safety profile was in this study. The registry’s study description says that DLTs informed estimation of the recommended Phase 2 dose for selected Part B combinations.

The endpoint is a participant count, not a measure of how severe every event was, how long a participant remained on treatment, or the overall frequency of all adverse events over the full study. Its specified time window is limited to Cycle 1. The registry record does not report the number of participants with a DLT, group-specific DLT counts, or an estimate of the recommended Phase 2 dose. Without those results, the primary endpoint cannot be interpreted quantitatively from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial design determines what statistical conclusions are supportable. This study is recorded as phase 1, nonrandomized, unmasked, and parallel-group. In a randomized trial, assignment by chance can help balance measured and unmeasured characteristics across groups. That protection is absent. Because regimen choice and dose groups were not randomized, differences across groups can reflect participant characteristics, cohort timing, dose selection, or other factors as well as treatment. This is a general design principle, not a claim that any particular factor affected this study.

What does the primary count represent?

The primary outcome is a count of participants who experienced a DLT during Cycle 1. A binary endpoint classifies each eligible participant as having or not having the event within its specified window. Counting participants makes the outcome interpretable as an event count, but it does not convey the full clinical detail of each event. It also does not describe events that occur outside the defined window. The registry record gives the DLT criteria and the primary endpoint population, but does not give the observed DLT results.

The endpoint population is defined as participants who received at least one dose before determination of the maximum tolerated dose and were observed for safety for 21 days after their first assigned dose, or experienced a DLT before 21 days. This definition sets a particular safety analysis group and observation rule. It should not automatically be assumed to apply to every other endpoint. The registry record does not report the analysis populations used for the listed secondary outcomes.

Why is dose escalation different from a treatment comparison?

Dose escalation seeks information about tolerability across doses and can guide later dose selection. Dose confirmation and expansion cohorts can further assess a selected regimen and explore outcomes in additional participants. These aims differ from estimating a treatment effect against a concurrent randomized control. In this study, Part A included favezelimab dose levels as monotherapy and with pembrolizumab, while Part B included several doses and combinations. Consequently, a group contrast would not have the same interpretation as a randomized comparison, even if numerical results were available.

How should event counts and percentages be understood?

A count reports how many participants were recorded with an event. A percentage expresses a count relative to a denominator, so the denominator and the event definition matter. Counts across groups of different sizes are not directly comparable as risks. General statistical practice would consider the proportion in each group and its uncertainty, but the registry record does not report a DLT proportion or confidence interval. The serious adverse-event summaries list affected participants and participants at risk by group; those are descriptive safety data and should not be treated as randomized contrasts.

For rare or uncommon events, estimates can be imprecise, especially in small cohorts. A confidence interval can communicate that uncertainty. Even when an interval is available, it does not correct confounding from nonrandomized assignment. The registry record does not report confidence intervals for the primary endpoint or the adverse-event counts described in the record.

What do pharmacokinetic outcomes add?

Pharmacokinetic endpoints describe drug exposure or concentration over time. The listed measures include area under the concentration-time curve for favezelimab and pembrolizumab, maximum serum concentration, and predose favezelimab concentration. In general, the area under the curve summarizes exposure over a specified interval, while maximum concentration describes a peak measurement. Such measures address exposure, not directly whether a treatment improves a clinical outcome. The registry record lists these endpoints but does not report their estimates in the registry record for this trial.

How should planning calculations be read?

Any sample-size figures associated with the results are planning illustrations, not observed power and not the trial’s own design justification. The stated assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For non-time-to-event outcomes, such illustrations refer to participants per arm; time-to-event illustrations refer to a total event count. These calculations depend on assumptions that may not match a nonrandomized, multi-cohort phase 1 study. They do not demonstrate that the study was designed or powered to test a specific treatment difference. The registry record does not report the trial’s sample-size justification or statistical plan.

Over-dispersion is a general concern when event data vary more than a statistical model expects; it can make standard errors too small if ignored. The primary endpoint is a participant count for a binary event, and no model or over-dispersion adjustment is reported in the registry record. It would therefore be inappropriate to infer a specific model or correction. The same caution applies to interim analyses, covariate adjustment, and missing-data methods: their use is not reported in the registry record.

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 A: Favezelimab 7 mg Monotherapy", "Part A: Favezelimab 21 mg Monotherapy", "Part A: Favezelimab 70 mg Monotherapy", "Part A: Favezelimab 210 mg Monotherapy", "Part A: Favezelimab 700 mg Monotherapy", "Part A: Favezelimab 7 mg + Pembrolizumab 200 mg")
n      <- c(3, 6, 3, 3, 3, 3)
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 A: Favezelimab 7 mg Monotherapy  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Part A: Favezelimab 21 mg Monotherapy  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Part A: Favezelimab 70 mg Monotherapy  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Part A: Favezelimab 210 mg Monotherapy  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Part A: Favezelimab 700 mg Monotherapy  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Part A: Favezelimab 7 mg + Pembrolizumab 200 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The study includes a primary safety endpoint and several secondary outcomes, including objective response rate and pharmacokinetic measures. Multiple outcomes create the general possibility of multiplicity: when many statistical tests are conducted, the chance of at least one apparently unusual result can increase. A prespecified testing hierarchy or adjustment can address some multiplicity concerns, but the registry record does not report a multiplicity procedure, testing hierarchy, or detailed statistical analysis plan.

The primary endpoint population is described specifically: participants had to receive at least one dose before determination of the maximum tolerated dose and meet the stated safety observation rule. That definition is reported for the DLT endpoint. The registry record does not report analysis populations for the secondary outcomes or explain whether all treated participants, evaluable participants, or another population was used for each one.

Missing outcome data can affect estimates when participants lack an assessment or leave the study before an outcome is measured. The record does not describe how missing DLT assessments, response evaluations, or pharmacokinetic measurements were handled. It also does not report imputation methods or sensitivity analyses. Those omissions mean the effect of missingness on the reported outcomes cannot be evaluated from this registry information.

The overall enrollment listed is 481, but the record does not provide a statistical rationale for that enrollment target. It also does not report whether interim analyses were planned or conducted. Since allocation was nonrandomized, any adjustment for differences in participant characteristics would be particularly relevant to comparative interpretation; such adjustment is not reported in the registry record. These gaps do not invalidate the descriptive information, but they limit how far inferential conclusions can be taken.

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: hypophysitis (33.3%), constipation (33.3%), gastric stenosis (33.3%), gastrointestinal haemorrhage (33.3%), nausea (33.3%).

The adverse-event summaries distinguish serious adverse events, other adverse events, and deaths. For example, the record lists 69 participants with serious adverse events among 205 at risk in the Part B favezelimab 200 mg plus pembrolizumab group, and 23 among 40 at risk in the Part B favezelimab, pembrolizumab, and lenvatinib group. These are descriptive group counts, not randomized treatment comparisons.

The record also lists other adverse events and deaths by group. Those categories should not be conflated: the counts describe different event classifications, and the death counts are not stated to be treatment-related. The registry record does not provide enough information in these summaries to infer causation, timing, duration, severity distribution, or whether participants experienced more than one event. Counts should not be added across categories or groups.

Several serious adverse-event terms are listed as 33.3%, including hypophysitis, constipation, gastric stenosis, gastrointestinal haemorrhage, nausea, and non-cardiac chest pain. The record does not establish from this listing alone a comparison across treatments. Small group sizes can make descriptive percentages unstable; this is a general statistical caution. The listed data do not establish that one regimen is safer than another.

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

The record documents a phase 1 study of favezelimab as monotherapy and in multiple combinations in adults with advanced solid tumors. Its design included dose escalation, dose confirmation, and expansion cohorts. The primary endpoint was a DLT count during the first 21 days, and the study also listed response and pharmacokinetic outcomes. These details explain the research questions the study was organized to address.

The record does not report the primary endpoint result, an estimated recommended Phase 2 dose, or the outcome estimates for objective response and pharmacokinetics in the trial details. It therefore does not support a numerical conclusion about DLT frequency or response. The recorded adverse-event counts provide descriptive safety information, but they do not by themselves establish whether an event was caused by a study treatment.

The nonrandomized design also limits treatment comparisons. Different regimens and doses were administered in different groups, without random allocation or masking. Even if outcome differences between groups were reported, they could not be attributed to treatment alone on the basis of this design description. The study is not a like-for-like controlled comparison.

In general, statistical uncertainty matters because estimates from limited cohorts may be imprecise. Confidence intervals and clearly defined analysis populations help readers assess that uncertainty, but the registry record does not report primary endpoint confidence intervals or a full statistical analysis plan. No advice about an individual’s care follows from these study details. The appropriate interpretation is limited to what the registry records: the study structure, endpoint definitions, listed adverse-event counts, and the absence of reported primary results in this record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the range of questions combined within an early-phase program. Part A focused on escalating doses of favezelimab alone or with pembrolizumab. Part B included dose confirmation and expansion across monotherapy, immunotherapy combinations, chemotherapy combinations, lenvatinib, and a coformulated product. Each objective calls for a different interpretation: dose tolerability, pharmacokinetic exposure, and response assessment are not the same statistical target.

The nonrandomized, parallel-group structure is central to interpreting any arm-level numbers. In a trial designed for dose development, groups may differ by dose, regimen, and study purpose. A numerical contrast between them cannot be treated as a clean causal estimate of the effect of one treatment versus another. Recognizing this prevents descriptive safety information from being mistaken for comparative evidence.

The primary endpoint’s restricted observation window is another important feature. DLTs were defined for Cycle 1, a 21-day period, while the study summary describes treatment over repeated cycles and possible additional treatment for some participants. Early-cycle toxicity is useful for dose development, but it does not describe the entire course of safety experience.

Finally, the record illustrates the importance of distinguishing endpoint definitions from endpoint results. The DLT criteria and target population are described, but the observed DLT counts are not reported in the registry information at hand. Without those results and the analysis details, readers should not infer a dose recommendation or a treatment effect. The study remains informative as a map of the questions and regimens assessed, while its comparative and outcome interpretation is limited by what the record reports.

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 registry record does not report the primary DLT result or a recommended Phase 2 dose estimate. It also does not report the listed objective response or pharmacokinetic outcome estimates. As a result, the clinical outcomes that would be needed to characterize the study’s efficacy and dose-selection findings are not available in this record.

The study was nonrandomized and unmasked, with multiple regimens and dose levels across cohorts. The groups are not like-for-like controls, so comparisons between their counts may reflect differences other than regimen. The record does not report detailed participant characteristics by group, adjusted comparisons, or a plan for controlling confounding.

The primary DLT window is limited to the first 21 days. It does not by itself summarize later toxicity or the full duration of treatment. Although the record lists serious adverse events, other adverse events, and deaths, it does not provide the event-level context needed to evaluate timing, recurrence, attribution, or overlap among categories. The record also does not describe missing-data handling or analysis populations for secondary outcomes.

The enrollment entry is 481, but a sample-size justification is not reported in the registry record. A statistical analysis plan, multiplicity approach, interim analysis information, and confidence intervals for the primary endpoint are also not reported in the registry record. These limitations restrict both the assessment of precision and the strength of any statistical interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Favezelimab (MK-4280) as Monotherapy and in Combination With Pembrolizumab (MK-3475) With or Without Chemotherapy or Lenvatinib (MK-7902) AND Favezelimab/Pembrolizumab (MK-4280A) as Monotherapy in Adults With Advanced Solid Tumors (MK-4280-001) — NCT02720068.
• Registry record last updated 2025-05-30; status last verified 2025-05.
• Results first posted 2025-05-30.
• 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

NCT02720068 is listed as a completed phase 1, nonrandomized, open-label, parallel-group study of favezelimab in adults with advanced solid tumors. The registry lists enrollment as 481, with a start date of 2016-05-02 and primary completion date of 2024-03-15. Study components included dose escalation and dose confirmation or expansion cohorts.

The primary endpoint was the number of participants with a dose-limiting toxicity during the first 21 days. Regimens included favezelimab alone and combinations with pembrolizumab, chemotherapy, lenvatinib, or the coformulated product MK-4280A. Secondary outcomes included objective response and pharmacokinetic measures. The registry record describes adverse-event counts by group, but does not report the primary endpoint result, response estimates, pharmacokinetic estimates, or a detailed statistical analysis plan.