A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors (NCT04158583), a non-randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0).

2. Clinical Question

The registry describes a study of RO7296682 in people with advanced and/or metastatic solid tumors. Its central question was whether the study treatment could be evaluated for safety and tolerability, with pharmacokinetics and pharmacodynamics also named in the official title. The primary outcome counted participants with adverse events (AEs) graded according to NCI CTCAE v5.0. An AE, as defined in the record, is an untoward medical occurrence after administration of a pharmaceutical product; it need not be caused by the treatment.

This is primarily a safety question, not a confirmatory comparison of treatment effects. The secondary outcomes include response, disease control, duration of response, on-treatment progression-free survival, and pharmacokinetic measures. The posted record does not report results for those outcomes. The trial’s non-randomized structure and varied tumor types mean that any differences between dose cohorts should not be read as causal comparisons.

3. Trial Design

This was an open-label, multicenter Phase 1 study with non-randomized allocation and a parallel model. The registry lists enrollment of 76 participants and the status as terminated. The recorded study start was 2019-12-09, and the primary completion date was 2022-07-21. These dates describe the registry record; they do not by themselves explain why the study was terminated or how its conduct changed over time.

The intervention was RO7296682, described in the official title as a CD25-targeting, T-regulatory cell depleting antibody. Part A contains ten dose cohorts: 0.3 mg, 1 mg, 2 mg, 6 mg, 18 mg, 35 mg, 70 mg, 100 mg, 165 mg, and 20 mg. The cohort order in the registry is not a simple ascending dose sequence, so the cohorts are best identified by their listed dose rather than treated as a sequence based on their numbering. Most descriptions specify intravenous administration on Day 1 of Cycle 1 and subsequent Q3W dosing; the record describes a cycle as 21 days for several cohorts. Some cohort descriptions are truncated, and the full dosing or toxicity-management details are not reported in the registry record.

The cohort descriptions name several tumor types, while the overall condition is listed as solid tumors. The study was unmasked, so participants and investigators were not blinded according to the registry’s masking field. The record does not report randomized assignment, an untreated comparison group, or a head-to-head comparator. Accordingly, the cohort data are descriptive safety observations, not randomized estimates of differences between doses.

The primary outcome is the number of participants with AEs graded according to NCI CTCAE v5.0. Its stated observation window runs from signing informed consent until the last follow-up visit, up to approximately 2 years 7 months. Although safety and tolerability were the stated purpose, the registry record does not report the full statistical analysis plan, dose-selection rules, interim decision criteria, or reasons for termination. Those details should not be inferred from the Phase 1 designation or the presence of multiple dose cohorts.

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 76 participants with non-small cell lung cancer (NSCLC), melanoma (MEL), head and neck squamous cell carcinoma (HNSCC), ovarian cancer (OvC), triple-negative breast cancer (TNBC), and esophageal carcinoma (EsC) were enrolled in Part A. No Participants were enrolled in Part B.

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: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not.

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: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), measured over From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months).

The primary endpoint counts participants with adverse events graded according to NCI CTCAE v5.0. The registry describes an AE as an unfavorable or unintended sign, symptom, disease, or abnormal laboratory finding temporarily associated with use of a medicinal product. Importantly, the definition does not require a causal relationship with the study treatment. An event counted as an AE therefore cannot automatically be described as a treatment-caused harm.

The observation window begins at informed consent and continues until the last follow-up visit, for up to approximately 2 years 7 months. That interval matters when reading participant counts: they describe whether participants had events during the stated follow-up, rather than the number of event episodes or an event rate per unit of time. The primary endpoint title specifies a participant count, not a comparison of event timing or severity distributions.

Safety endpoints are used in early-phase studies to characterize observed tolerability and identify events that merit continued monitoring as treatment is studied. In general, counting participants with events gives a direct description of how many people experienced at least one event within the defined period. It does not, by itself, distinguish background illness from treatment-related effects, quantify exposure-adjusted risk, or establish a causal effect. Interpretation also depends on how the event categories and analysis populations are defined and reported.

The registry record names a safety population consisting of participants who received at least one dose, but its wording also says “randomized to study treatment,” despite the trial’s non-randomized allocation. The number analyzed for the primary outcome and detailed endpoint results are not reported in the registry record. The posted adverse-event group data can therefore be described as reported cohort counts, while the exact analytic correspondence between those counts and the stated primary endpoint is not fully documented.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the design. This study is non-randomized and has no listed control arm. In general, random assignment helps balance measured and unmeasured participant characteristics across treatment groups. Without randomization, cohort differences may reflect differences in who entered each cohort, when they were treated, how long they were followed, or other factors. The registry does not report enough detail to assess those influences. Comparisons among cohorts are thus descriptive and should not be treated as unbiased estimates of dose effects.

What does a participant count represent?

The primary endpoint is a count of participants with AEs, rather than a count of every event episode. In general, this kind of endpoint records whether a participant had at least one qualifying event during the specified observation period. One participant with several events may still contribute once to a participant-level count for a particular outcome, depending on the outcome definition. A count does not show when an event occurred, how long it lasted, or how many episodes occurred. The registry does not report additional event-level analyses in the information summarized for this study.

The record defines AEs broadly and says that they need not be causally related to treatment. This is a standard distinction in safety reporting: an event observed after treatment is not automatically an adverse reaction caused by treatment. Attribution generally requires clinical assessment and cannot be inferred from the mere presence of an AE in a treatment cohort. The causal attribution process and any treatment-related event results are not reported in the registry record.

Why distinguish serious events from other events?

Serious adverse events are a safety category distinct from the broader AE concept. The posted data give cohort counts for participants at risk and affected by serious events, as well as counts for participants affected by other adverse events. In general, separate categories help readers distinguish outcomes with different reporting definitions, but the labels do not disclose every detail of event severity, timing, relatedness, or recurrence. The precise definition used for the “other” category is not reported in the registry record, so it should not be assigned a more specific interpretation.

The unit “participants” matters. A participant count does not equal the number of events, and it does not incorporate person-time. In general, an event rate accounts for the amount of time participants are observed or exposed; a simple count does not. Here, the endpoint’s follow-up window is stated, but cohort-specific exposure and follow-up durations are not reported in the registry record. Consequently, the group counts alone cannot support exposure-adjusted comparisons.

What can confidence intervals and tests add?

In general, a confidence interval describes a range of values compatible with the observed data and a specified statistical procedure. It communicates uncertainty as well as the direction and magnitude of an estimate. A p-value, in general, summarizes how unusual the observed data would be under a specified null model; it does not measure the probability that a treatment works, nor does it establish causality. Neither confidence intervals nor p-values for the primary safety outcome are reported in the registry record. With small cohort counts, uncertainty would be important to characterize, but no new inferential result can be obtained from the posted figures without defining an analysis and its assumptions.

The registry identifies 16 outcome measures and lists several secondary outcomes, including response measures, on-treatment progression-free survival, and pharmacokinetic measures. It lists zero analyses in the record information. That does not establish that no analyses were conducted; it means analysis results and specifications are not reported in the registry record information. Endpoint-specific analysis populations, missing-data procedures, covariate adjustments, and multiplicity procedures are also not reported.

How should the planning illustration be understood?

The registry’s sample-size assumptions describe a planning illustration computed from an observed effect, not the design rationale used to plan this trial. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. In general, such an illustration asks how many participants might be needed under those assumptions to detect an effect of a chosen size. It is not an estimate of the probability that the completed study detected an effect, and it is not observed power.

The posted illustration is not a substitute for the trial’s own sample-size justification. Its two-arm equal-allocation setup does not match the listed non-randomized cohort structure as a direct comparison. The trial’s sample-size justification and any prespecified target effect are not reported in the registry record. Values for planning scenarios should be treated as hypothetical design calculations rather than evidence from the enrolled participants.

Finally, the safety population wording merits care. The record describes it as all participants “randomized to study treatment” who received at least one dose, while the allocation field describes the study as non-randomized. This wording does not resolve how the analysis population was operationalized. In general, analysis-population definitions should align with the design and clarify which participants contribute to each endpoint. The record’s wording and the absence of detailed analysis documentation limit verification of that alignment.

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: Cohort 1 RO7296682 0.3 mg Q3W", "Part A: Cohort 2 RO7296682 1 mg Q3W", "Part A: Cohort 3 RO7296682 2 mg Q3W", "Part A: Cohort 4 RO7296682 6 mg Q3W", "Part A: Cohort 5 RO7296682 18 mg Q3W", "Part A: Cohort 6 RO7296682 35 mg Q3W")
n      <- c(5, 5, 6, 14, 8, 5)
events <- c(5, 5, 6, 14, 8, 5)
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: Cohort 1 RO7296682 0.3 mg Q3W  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  Part A: Cohort 2 RO7296682 1 mg Q3W  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  Part A: Cohort 3 RO7296682 2 mg Q3W  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Part A: Cohort 4 RO7296682 6 mg Q3W  14  14  100.0  76.8  100.0  78.5  100.0  78.2  99.8
ARM  Part A: Cohort 5 RO7296682 18 mg Q3W  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  Part A: Cohort 6 RO7296682 35 mg Q3W  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures. The named secondary outcomes include Objective Response Rate, Disease Control Rate, Duration of Response, On-Treatment Progression Free Survival, and pharmacokinetic measures such as AUC, Cmin, Cmax, and total clearance. The record also gives a total of 16 outcome measures. When many outcomes are tested, the chance of at least one apparently notable result can increase. In general, multiplicity procedures define how interpretation or statistical testing accounts for multiple outcomes, comparisons, or analysis time points.

Multiplicity handling is not reported in the registry record. The number of analyses listed is zero, and no p-values or other inferential results for the outcomes are reported. It is therefore not possible to determine whether a particular outcome was treated as primary for formal testing, whether secondary outcomes were exploratory, or whether any adjustment was used. No multiplicity adjustment should be assumed.

Missing-data rules are also not reported in the registry record. The registry states that the safety population included participants who received at least one dose, but also describes those participants as randomized, which does not match the non-randomized allocation field. The number included in each endpoint analysis, the handling of participants with incomplete follow-up, and the reasons for any missing observations are not reported. In general, missingness can affect safety summaries if participants with less follow-up have fewer opportunities for events to be observed.

The observation period is described as running from informed consent until the last follow-up visit, up to approximately 2 years 7 months. That maximum does not establish that every participant had the same follow-up duration. The record does not report participant-level follow-up, exposure time by cohort, or censoring details. These omissions limit interpretation of raw counts and prevent assessment of how missing follow-up may have influenced the findings.

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: small intestinal obstruction (20.0%), covid-19 pneumonia (20.0%), pneumonia (20.0%), pneumonitis (20.0%), fatigue (16.7%).

Serious adverse-event figures are presented as participants at risk and participants affected within each dose cohort. For example, the 6 mg cohort has 14 participants at risk and 7 affected, while the 2 mg and 35 mg cohorts each list zero affected among their respective participants at risk. These are observed participant counts, not event rates adjusted for exposure time. The counts should not be used to rank doses, since participants were not randomized among cohorts and the record does not provide information needed to establish comparable follow-up or participant characteristics.

The separate counts for other adverse events indicate participants affected in that category, but the category’s exact definition is not reported in the registry record. Counts of deaths are listed by cohort, but the information does not establish cause or attribution. Similarly, the listed serious-event terms and percentages describe the record’s reported summary; the denominator and selection procedure for those terms are not reported in the registry record.

In general, safety reporting distinguishes events observed during a study from events judged related to a treatment. The registry’s AE definition explicitly allows events without a causal relationship. Therefore neither a serious-event count nor a death count should automatically be described as caused by RO7296682. The figures are useful as descriptive safety observations, with limited precision and no randomized comparator.

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

The posted results describe adverse-event experience across non-randomized RO7296682 dose cohorts in a Phase 1 study of participants with advanced solid tumors. They include counts of participants affected by serious events, counts for other adverse events, and death counts, together with a short list of serious-event terms and percentages. The primary endpoint is a participant count of AEs graded using NCI CTCAE v5.0 over the stated follow-up period.

These findings do not establish that RO7296682 caused any particular event. The registry’s AE definition does not require causation, and the event counts do not provide an attribution analysis. The figures also do not show that one dose is safer than another. Because allocation was non-randomized and no control group is listed, differences between cohorts are not controlled comparisons. They may reflect participant characteristics, exposure, follow-up, chance, or other factors that are not documented in the registry record.

The counts do not provide a precise estimate of risk for a broader population. Cohort sizes are limited, and the registry does not report confidence intervals, inferential tests, cohort-specific observation time, or detailed exposure information. A cohort with no listed serious events should not be interpreted as establishing that the event is impossible or absent from the population. Conversely, a listed event does not alone prove a treatment-related hazard.

The study’s secondary objectives cover response, progression, and pharmacokinetics, but their results are not reported in the registry record. Consequently, these safety data do not answer whether the treatment changes tumor response or disease progression. Nor do the posted data clarify the reason for termination, the trial’s dose-escalation decision process, or its statistical analysis plan. The most defensible reading is descriptive: the registry records safety observations by cohort, while key details for causal, comparative, and precision-based interpretation are unavailable.

14. Why This Trial Matters Statistically

This trial illustrates a common statistical challenge in early-phase research: describing safety across small, non-randomized dose cohorts. Such studies can contribute structured observations about events during treatment and follow-up, but the design does not automatically support dose-to-dose causal conclusions. Clear separation between description and comparison is essential, particularly when cohort sizes are small and the treatment groups may not be comparable.

It also demonstrates why endpoint definitions matter. The primary outcome counts participants with AEs, while the posted safety data distinguish serious events, other events, and deaths. Those are different summaries, and none alone provides event timing, recurrence, exposure-adjusted rates, or treatment attribution. Statistical interpretation depends on matching each count to its definition, population, and observation window.

The record further shows how incomplete analysis reporting constrains interpretation. Without analysis methods, uncertainty estimates, missing-data rules, or a clear account of multiplicity, readers cannot assess inferential precision or determine how the listed outcomes were evaluated. The population definition’s reference to randomization also sits uneasily beside the non-randomized design, underscoring the value of internally consistent registry descriptions.

Finally, a planning illustration should not be mistaken for trial evidence. The stated sample-size assumptions describe a hypothetical calculation from an observed effect, rather than the trial’s own design justification or an observed-power result. Distinguishing planning calculations from observed data helps prevent an analysis assumption from being interpreted as a study finding. Together, these considerations make this record a useful example of why design, endpoint definitions, denominators, and analysis reporting must all be considered when reading safety counts.

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 information available for this trial supports descriptive interpretation but leaves substantial uncertainty about the analysis. The registry lists a non-randomized design, no masking, and multiple dose cohorts, without a listed control group. Consequently, the posted cohort counts cannot isolate the effect of dose from differences in participant mix, exposure, or follow-up. The registry record does not report characteristics by cohort or cohort-specific time at risk.

Although the primary endpoint definition is broad and specifies NCI CTCAE v5.0, primary endpoint analysis results are not separately reported in the record information summarized. The record does not provide confidence intervals, p-values, participant-level event timing, exposure-adjusted rates, or detailed attribution results. The exact definition of the “other” adverse-event grouping and the denominator used for the listed serious-event term percentages are not reported in the registry record.

The stated safety-population wording refers to participants randomized to treatment despite the non-randomized allocation. The record does not clarify the operational analysis population or how many participants contributed to each endpoint. Missing-data handling, follow-up completeness, and reasons for incomplete observations are not reported. Some cohort descriptions are truncated, including the 0.3 mg cohort description, limiting the available dosing detail.

The study is listed as terminated, but the reason for termination is not reported in the registry record. The protocol’s dose-selection criteria, interim analyses, sample-size justification, and full statistical analysis plan are also not reported. The registry lists secondary outcomes but does not report their results in this record information. These limitations prevent conclusions beyond the descriptive safety observations and should be kept in view when interpreting counts across cohorts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors — NCT04158583.
• Registry record last updated 2024-03-04; status last verified 2023-07.
• Results first posted 2024-03-04.
• 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

NCT04158583 is an open-label, multicenter, non-randomized Phase 1 study of RO7296682 in participants with advanced and/or metastatic solid tumors. The registry lists enrollment of 76 participants, a parallel model, and ten Part A dose cohorts. The study is marked terminated, with a recorded start of 2019-12-09 and primary completion on 2022-07-21.

The primary endpoint counts participants with AEs graded using NCI CTCAE v5.0 from informed consent until the last follow-up visit, up to approximately 2 years 7 months. Posted safety information includes serious-event counts by cohort, counts for other adverse events, deaths, and selected serious-event terms. These are descriptive observations, not randomized comparisons or proof of treatment causation.

The record does not report inferential safety results, detailed missing-data procedures, the analysis plan, or results for the listed secondary outcomes. It also does not report why the study was terminated. Interpret the cohort figures in light of the non-randomized design and the missing analysis detail.