A Study of Etigilimab and Nivolumab in Participants With Locally Advanced or Metastatic Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Etigilimab and Nivolumab in Participants With Locally Advanced or Metastatic Tumors (NCT04761198), a non-randomized phase 1, phase 2 study. The primary outcome is Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1).

2. Clinical Question

The study also set out to assess safety, tolerability, pharmacokinetics, and pharmacodynamics. Secondary outcomes include disease control rate, duration of response, duration of stable disease, serum concentrations of etigilimab, and anti-drug antibodies to etigilimab. Those aims provide a wider description of treatment exposure and observed clinical events, but they do not create a randomized comparison. Without a control group, differences between the tumor-specific cohorts cannot be interpreted as causal treatment effects.

3. Trial Design

This was a phase 1b/2, multicenter, open-label, non-randomized study with a parallel model. The registry lists an enrollment of 76 participants and a completed status. The recorded start date is 2021-03-23, and the primary completion date is 2023-10-30. The sponsor is Mereo BioPharma.

Participants received etigilimab with nivolumab. The brief description specifies nivolumab at 240 milligrams every 2 weeks and etigilimab every 2 weeks. The cohort descriptions state that treatment continued until protocol-defined discontinuation criteria were met. Specific details of those criteria are not reported in the registry record.

The named cohorts span multiple tumor settings: endometrial cancer without prior CPI treatment, head and neck squamous cell carcinoma, cervical carcinoma, recurrent advanced and/or metastatic gastric or gastroesophageal junction adenocarcinoma, TMB-H and MSS solid tumors, rare tumors including sarcoma, uveal melanoma, and germ cell tumors, endometrial cancer after PD-1/PD-L1 treatment, and ovarian cancer. The safety record contains groups for Cohorts A, B, C, E, F, G, and H; safety figures for Cohort D are not reported in the registry record.

There was no masking and no random allocation. Because participants were not assigned by randomization to a control treatment, the study is best read as a collection of treated cohorts rather than a controlled comparison. Cohort populations differ by tumor type and treatment history, and their sizes vary. These design features affect how response and safety findings can be interpreted: observed outcomes describe the participants who received the combination, while the study design does not isolate the combination's effect from other explanations.

The registry lists no analysis entries. The planned sample-size justification, any interim analysis plan, and a full statistical analysis plan are not reported in the registry record. The endpoint description does specify that objective response was assessed using RECIST v1.1 and defines the response-evaluable population, although the population wording is incomplete in the 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.

Before assignment: Cohort D (Recurrent advanced and/or metastatic gastric or gastroesophageal junction adenocarcinoma) did not enroll any participants due to closure of the cohort by the Sponsor.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: RE Analysis Set included all participants with measurable disease at baseline who received study drug and had at least 1 post-baseline response assessment or discontinued treatment due to disease progression (including death due to disease progression) within 16 weeks (+ a 2-week window) of the first dose of study drug. Per planned analysis, the efficacy data for Cohort F were collected and analyzed separately per tumor type.

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 Analysis Set included all participants who received any amount of study drug.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR) as Assessed Based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1), measured over From first dose of study drug until the date of first objective response (CR or PR) (maximum exposure: 638 days).

The primary endpoint is objective response rate (ORR), defined as the percentage of participants whose best overall response was a confirmed complete response or confirmed partial response under RECIST v1.1. A complete response requires disappearance of target and non-target lesions and normalization of tumor marker level; pathological lymph nodes must meet the specified size criterion. A partial response requires at least a 30% decrease in the sum of target-lesion diameters from baseline.

ORR is used to describe the proportion of participants meeting a prespecified tumor-response definition during assessment. It is a binary outcome at the participant level: each participant either meets the complete-or-partial-response definition or does not. Reporting a percentage with a 95% confidence interval can show both the estimated response proportion and the uncertainty around that estimate. The registry record identifies a 95% confidence interval as the measure of dispersion, but the estimate, interval, and number of responders are not reported in the registry record.

The endpoint timeframe runs from first dose until the date of first objective response, with a maximum exposure of 638 days. The population is described as participants with measurable disease at baseline who received study drug and had at least one post-baseline response assessment, or who discontinued due to disease progression within a stated period. The population description is cut off in the registry record, so its complete criteria are not available.

ORR focuses on confirmed tumor shrinkage and does not, by itself, describe how long a response lasts, whether disease remained stable, or how outcomes compare with another treatment. The study lists duration of response, duration of stable disease, and disease control rate among its secondary outcomes, but their results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry defines the primary endpoint as a percentage, with a 95% confidence interval. Its response definition is based on RECIST v1.1 and counts participants whose best overall response is a confirmed complete response or confirmed partial response. The registry gives clinical definitions for these categories, but does not report how the confidence interval was calculated or provide the observed response data.

What does a percentage endpoint represent?

General statistical explanation: a percentage for a binary endpoint is based on the number of participants meeting the event definition relative to the number included in the relevant analysis population. Each participant contributes an event status under the endpoint rules. The estimated percentage describes the observed proportion in that analysis population; it is not automatically an estimate of what would happen in a different population or under a different treatment setting. In this record, the event is confirmed complete or partial response. The number of responders and the analyzed denominator are not reported in the registry record, so the percentage cannot be interpreted numerically.

How should the confidence interval be understood?

General statistical explanation: a confidence interval expresses sampling uncertainty around an estimate, under the method and assumptions used to construct it. It helps readers distinguish a relatively precise estimate from one with substantial uncertainty. Its width depends on factors including the number of observations and the observed event pattern. The registry specifies a 95% confidence interval for ORR, but does not name the interval method or report its limits. No specific degree of precision can therefore be described for the primary result.

Why does the analysis population matter?

The endpoint is not defined over every enrolled participant without qualification. The registry describes a RE Analysis Set that includes participants with measurable disease at baseline who received study drug and had at least one post-baseline response assessment, or who discontinued treatment because of disease progression within a specified window. The wording of the window ends incompletely in the registry record. This means the complete operational population definition cannot be reconstructed from the record. In general, eligibility for an analysis population affects both the numerator and denominator of a percentage endpoint. How participants with no assessment for reasons other than progression were handled is not reported in the registry record.

What is the role of RECIST v1.1?

RECIST v1.1 provides rules for classifying changes in measurable tumors. The registry states that a complete response requires disappearance of target and non-target lesions, normalization of tumor marker level, and a reduction in the short axis of any pathological lymph node to <10 millimeters. A partial response requires at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as reference. Requiring confirmation means the response must meet the protocol's confirmation rule, although the timing and details of that rule are not reported in the registry record. Use of a defined response framework supports consistent classification; it does not remove uncertainty from a small or selected cohort or establish a treatment effect without a comparison group.

What can be learned from the study design?

General statistical explanation: random allocation is one way to balance measured and unmeasured prognostic factors across treatment groups, on average. This study was non-randomized and had no like-for-like control arm. Therefore, an observed response proportion would be descriptive of treated participants and could not by itself separate treatment effects from natural disease course, participant selection, other care, or differences in assessment. Open-label status means masking was absent; the registry does not report additional safeguards against assessment bias.

The parallel model describes separate groups assessed during the same study, rather than a crossover in which the same participant receives treatments in sequence. Here the named cohorts are defined by tumor type and treatment history. Their outcomes should not be treated as a randomized comparison across groups. Cohort sizes differ, and the registry's safety figures show groups ranging from 1 at risk in Cohort B to 33 at risk in Cohort F. These counts are context for the safety results; they are not evidence of comparative efficacy.

What methods are not specified?

The registry record does not report the method used to calculate the 95% confidence interval, the detailed response assessment schedule, the approach to missing or unevaluable assessments, or a full statistical analysis plan. It does not list analyses, interim analyses, or a sample-size justification. These omissions matter because analysis choices can change the estimate, interval, or interpretation. No method should be inferred solely from the endpoint type or from common practice.

General statistical explanation: for a binary outcome, estimates from small groups can be unstable, and intervals may be wide. Pooling groups can improve numerical precision only if a combined estimate is meaningful for the populations being combined. Since this study includes different tumor settings and treatment histories, any pooled analysis would need a stated rationale and population definition. The record does not report such an analysis or its results. The key methodological conclusion is thus limited: the endpoint and some of its response rules are specified, but the numerical primary result and several details needed to evaluate its analysis are 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("Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naiv", "Cohort B: Head and Neck Squamous Cell Carcinoma", "Cohort C: Cervical Carcinoma", "Cohort E: TMB-H + MSS Solid Tumors", "Cohort F: Rare Tumors (Uveal)", "Cohort F: Rare Tumors (De-diff LPS)")
n      <- c(10, 1, 8, 9, 8, 10)
events <- c(2, 0, 3, 0, 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  Cohort A: Endometrial Cancer CPI (PD-1/PD-L1) Naiv  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8
ARM  Cohort B: Head and Neck Squamous Cell Carcinoma  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Cohort C: Cervical Carcinoma  8  3  37.5  8.5  75.5  13.7  69.4  13.7  70.1
ARM  Cohort E: TMB-H + MSS Solid Tumors  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Cohort F: Rare Tumors (Uveal)  8  2  25.0  3.2  65.1  7.1  59.1  7.5  60.0
ARM  Cohort F: Rare Tumors (De-diff LPS)  10  1  10.0  0.3  44.5  1.8  40.4  2.3  41.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, objective response rate, and seven secondary outcome types. The secondary outcomes cover treatment-emergent adverse events and selected adverse-event categories, disease control rate, duration of response, duration of stable disease, serum concentrations of etigilimab, and anti-drug antibodies to etigilimab. The numerical results for these outcomes are not reported in the registry record.

When a study examines multiple outcomes, subgroups, or time points, the chance of at least one apparently notable result can increase if each is interpreted as a separate confirmatory test. General statistical explanation: multiplicity procedures can control that risk by adjusting testing or by specifying a hierarchy of hypotheses. The registry record does not report a multiplicity strategy, inferential hierarchy, or detailed statistical analysis plan. It is therefore not possible to determine whether secondary outcomes were intended as confirmatory or exploratory, or how multiple analyses were handled.

The primary endpoint applies to a defined response-evaluable set. The record describes participants with measurable disease at baseline who received study drug and had at least one post-baseline response assessment, or discontinued because of progression within a specified period. The population description is incomplete, and the full criteria are not reported in the registry record. The number enrolled was 76, but the number in the primary analysis population and the number excluded from it are not reported in the registry record.

The record does not explain how missing response assessments were handled, whether participants without an evaluable assessment were counted as nonresponders, or how incomplete follow-up affected secondary outcomes. It also does not report missing-data proportions. These are important distinctions: the percentage among evaluable participants can differ from one based on all enrolled participants if participants without outcome assessments are treated differently. No such difference can be quantified from the registry record.

The registry does not list analysis entries or interim analyses. The sample-size justification and detailed analysis plan are also not reported in the registry record. Thus the available description identifies endpoint names and some population criteria, but not enough to assess prespecified testing procedures, missing-data handling, or the full analysis populations.

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: sepsis (25.0%), urinary tract obstruction (25.0%), acute kidney injury (25.0%), pleural effusion (20.0%), pneumonia (12.5%).

The registry reports serious adverse-event counts by cohort, alongside the number at risk in that cohort. Cohort A lists 2 participants affected among 11 at risk; Cohort B lists 0 among 1; Cohort C lists 2 among 8; Cohort E lists 5 among 9; Cohort F lists 8 among 33; Cohort G lists 2 among 4; and Cohort H lists 3 among 10. Serious adverse-event figures for Cohort D are not reported in the registry record. These are cohort-specific counts, not randomized comparisons.

The cohort denominators differ, so a count alone does not give the same context across groups. Small groups are especially difficult to compare, and tumor setting, participant characteristics, and exposure may also differ; those details are not fully reported in the safety summary. The figures should not be combined into a new overall rate without the appropriate definitions and analysis.

The registry lists serious adverse-event terms with percentages: sepsis, 25.0%; urinary tract obstruction, 25.0%; acute kidney injury, 25.0%; pleural effusion, 20.0%; pneumonia, 12.5%; and immune-mediated gastritis, 12.5%. The denominator and calculation basis for these percentages are not reported in the registry record. They should not be interpreted as percentages of all enrolled participants or as treatment-attributable risks without that information. The safety data are descriptive and do not establish that a particular event was caused by the combination.

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

The registry record establishes that a phase 1b/2, open-label study of etigilimab plus nivolumab was completed, with 76 participants enrolled. It identifies RECIST v1.1 objective response rate as the primary endpoint and describes confirmed complete and partial response criteria. It also lists safety and other secondary outcomes. These details clarify what the investigators intended to measure and the settings in which participants were treated.

The record does not report the primary response percentage, response count, or 95% confidence interval. Therefore, the magnitude and precision of the primary endpoint cannot be assessed from the registry record. Completion status does not indicate what the response results were. The listed secondary outcome names likewise do not establish findings; their results are not reported in the registry record.

Even if an ORR estimate were available, its interpretation would remain descriptive in this design. The study was non-randomized, open-label, and lacked a like-for-like control group. Observed responses could not be attributed to the treatment combination alone on the basis of this design. The cohorts also represent different tumor types and treatment histories, so the response of one group would not necessarily apply to another.

The safety counts document participants affected by serious adverse events in several cohorts, and the record names selected serious-event terms. Those observations are useful descriptions of events recorded during the study, but the available information does not establish causation or provide the denominator details for the listed percentages. No clinical recommendation follows from these statistics.

In general, a study endpoint is evidence about a defined population, measurement rule, and analysis. Here, the endpoint definition is partly available, but the outcome estimate and important analysis details are absent. The appropriate conclusion is that the registry describes the study question and some safety observations, while leaving the primary efficacy result and its uncertainty not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for the gap between a clearly named primary endpoint and the numerical result needed to interpret it. The registry specifies ORR as the primary outcome, identifies RECIST v1.1, defines confirmed complete and partial response, and states that a 95% confidence interval was intended to accompany the percentage. Yet the ORR estimate, its interval, and the responder count are not reported in the registry record. Readers can identify the intended measurement but cannot evaluate its observed value or precision.

The design also illustrates why endpoint estimates need their study context. This was a non-randomized, open-label study with parallel tumor-specific cohorts and no like-for-like control. A response percentage would describe outcomes in the analyzed treated population, not a controlled treatment contrast. Comparisons among cohorts would be vulnerable to differences in tumor type, treatment history, and cohort size. The varying sizes recorded in safety groups make that issue concrete.

For clinical researchers, the record highlights several distinct layers of interpretability: how response is defined, who enters the analysis population, how uncertainty is quantified, and whether the design supports causal comparisons. The response rules are partly described, while the population wording is incomplete and the confidence-interval method is not reported. Missing-data handling, multiplicity, and the full statistical analysis plan are also not reported in the registry record.

These are not technical details separate from the result. They determine what population a percentage describes, how much confidence to place in it, and which conclusions the design can support. In this case, the available information supports a careful description of the study framework and reported safety counts, but not an estimate of the primary efficacy outcome or a comparative efficacy conclusion.

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 central limitation for interpreting efficacy is that the registry record does not report the primary ORR result. No response percentage, response count, or 95% confidence interval is available. The record also lists no analysis entries, and numerical results for the listed secondary outcomes are not reported in the registry record. Accordingly, the primary outcome cannot be evaluated for magnitude, precision, or consistency across tumor cohorts.

The study was non-randomized and open-label, without a control group. There is therefore no like-for-like comparison to separate outcomes associated with the combination from other explanations. Cohorts were organized around different tumor types and treatment histories, and their sizes varied. Any apparent differences across cohorts would not be randomized treatment contrasts.

The primary analysis population description is incomplete. It identifies participants with measurable disease at baseline who received study drug and had at least one post-baseline response assessment, or discontinued due to progression within a stated period, but the complete wording is not reported in the registry record. The analyzed denominator, exclusions, and handling of participants without evaluable assessments are also not reported. The method for calculating the 95% confidence interval is not reported.

The registry does not report a full statistical analysis plan, sample-size justification, interim analysis plan, multiplicity approach, or procedures for missing outcomes. These omissions prevent assessment of whether reported analyses followed prespecified rules or how uncertainty and multiple outcomes were addressed.

Safety data are available for several cohorts, but not Cohort D. The cohort denominators differ, and the denominator and calculation basis for the listed serious-event percentages are not reported. These descriptive data do not establish causation. Together, these limitations restrict the record to a description of design, endpoint definitions, and selected safety counts; they do not permit a full statistical assessment of efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Etigilimab and Nivolumab in Participants With Locally Advanced or Metastatic Tumors — NCT04761198.
• Registry record last updated 2025-03-17; status last verified 2025-03.
• Results first posted 2025-03-17.
• 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

NCT04761198 is a completed phase 1b/2, multicenter, open-label, non-randomized study of etigilimab plus nivolumab in participants with locally advanced or metastatic solid tumors. The registry lists 76 enrolled participants and tumor-specific parallel cohorts. Nivolumab was described at 240 milligrams every 2 weeks, with etigilimab also administered every 2 weeks.

The primary endpoint was RECIST v1.1 objective response rate, defined by confirmed complete or partial response, with a 95% confidence interval specified. The primary result and numerical results for the listed secondary outcomes are not reported in the registry record. The record includes serious adverse-event counts for Cohorts A, B, C, E, F, G, and H, plus selected event terms and percentages; Cohort D safety figures and the percentage denominators are not reported.

Because there was no randomized control group, the study is descriptive rather than a controlled treatment comparison. Analysis details for missing data, multiplicity, and the full response-evaluable population are not reported in the registry record.