This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Nivolumab Combined With Ipilimumab and Nivolumab Alone in Patients With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H) (NCT03668119), a randomized phase 2 study. The primary outcome is Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03668119 |
| Phase | Phase 2 |
| Condition | Pan Tumor |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 212 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced or metastatic solid tumors of high tumor mutational burden (TMB-H) were studied. The primary endpoint population is described as all participants randomized in a salvage setting to arm A by TMB-High status. The registry record does not report further details about the eligible tumor types or how the high tumor mutational burden status was established.
Intervention
Arm A received nivolumab combined with ipilimumab. The study description identifies the trial as a randomized, open-label, phase 2 study. The registry record does not provide arm-specific dosing details in the arm descriptions.
Comparator
Arm B received nivolumab monotherapy. Although the study randomized participants between a combination and monotherapy strategy, the listed primary outcome is an Arm A response rate rather than a direct comparison between the arms. An Arm B objective response rate assessed by blinded independent central review is listed as a secondary outcome.
Primary question
The primary endpoint asks what percentage of participants in arm A had a confirmed complete or partial response, as assessed by blinded independent central review. It is an assessment of response in the combination arm, not a stated test of whether the combination differs from nivolumab alone. The registry record does not report the observed percentage or its confidence interval, so the magnitude and precision of the response rate cannot be evaluated from this record.
3. Trial Design
This is a randomized, open-label, parallel-group phase 2 study of nivolumab with ipilimumab or nivolumab alone in participants with advanced or metastatic solid tumors with high tumor mutational burden. The registry lists pan-tumor disease and an enrollment of 212. The study status is completed. The recorded start date is 2018-10-31, and the primary completion date is 2022-05-03.
The two named randomized treatment arms are nivolumab plus ipilimumab and nivolumab monotherapy. The registry describes the study purpose as assessing clinical activity of the combination across tumor types based on tumor mutational burden status. However, the primary outcome is specifically the objective response rate in arm A, the combination arm. The primary outcome is not recorded as a statistical comparison of response between the randomized arms. An Arm B response rate assessed by blinded independent central review is listed among the secondary outcomes.
Open-label means the trial is recorded as having no masking. The primary response assessment nevertheless uses blinded independent central review (BICR), which is a separate assessment feature: the outcome description says that response is determined by reviewers who are blinded. The registry does not provide details about the reviewers, the blinding procedures, or how disagreements were handled.
The primary endpoint timeframe is from randomization up to 42 months. The record lists additional outcomes involving response, duration of response, time to response, and clinical benefit, with assessments by investigators or BICR. It also lists a nivolumab-plus-ipilimumab rollover group in the adverse-event information. That rollover group is named separately from the two randomized arms. The registry record does not report the rationale, eligibility rules, or analysis role for the rollover group.
The record does not report the planned allocation ratio, treatment schedules, sample-size justification, or a statistical analysis plan. The recorded enrollment should therefore be read as the study's enrollment figure, not as evidence that any particular analysis was adequately powered.
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: Salvage setting describes participants with a refractory, metastatic, or unresectable histologically or cytologically confirmed solid malignant tumor with Tumor Mutational Burden-High (TMB-H) who are refractory to standard therapies per local management guidelines, or for which no standard treatment per local management guidelines is available. Participants randomized to the Nivolumab monotherapy arm B were allowed to rollover to Nivolumab+Ipilimumab arm A at the time of progression.
Pre-treatment
| Stage | Arm A: Nivolumab+Ipilimumab | Arm B: Nivolumab |
|---|---|---|
| STARTED | 136 | 76 |
| bTMB-H Started | 80 | 45 |
| tTMB-H Started | 88 | 47 |
| COMPLETED | 135 | 76 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Arm A: Nivolumab+Ipilimumab | Arm B: Nivolumab |
|---|---|---|
| Disease Progression | 1 | 0 |
Treatment
| Stage | Arm A: Nivolumab+Ipilimumab | Arm B: Nivolumab |
|---|---|---|
| STARTED | 135 | 76 |
| bTMB-H Started | 83 | 47 |
| tTMB-H Started | 94 | 50 |
| Arm B Rollover | 0 | 22 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 135 | 76 |
Reasons for not completing this period:
| Reason | Arm A: Nivolumab+Ipilimumab | Arm B: Nivolumab |
|---|---|---|
| Disease Progression | 76 | 57 |
| Study drug toxicity | 19 | 1 |
| Death | 3 | 0 |
| Adverse Event unrelated to Study drug | 4 | 3 |
| Withdrawal by Subject | 1 | 1 |
| Participant request to discontinue study treatment | 3 | 1 |
| Maximum Clinical Benefit | 0 | 1 |
| Participants completed treatment | 27 | 11 |
| Other reasons | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: All participants randomized in a salvage setting to arm A by TMB-High status
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.
| Characteristic | Unit | Arm A: Nivolumab+Ipilimumab | Arm B: Nivolumab | Total |
|---|---|---|---|---|
| Participants analysed | 136 | 76 | 212 | |
| Age, Continuous | Years | 60.0 (SD 11.7) | 57.6 (SD 12.1) | 59.2 (SD 11.9) |
| Sex: Female, Male: Female | Participants | 71 | 44 | 115 |
| Sex: Female, Male: Male | Participants | 65 | 32 | 97 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 13 | 5 | 18 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 45 | 20 | 65 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 78 | 51 | 129 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 6 | 3 | 9 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 124 | 60 | 184 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 5 | 12 | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A, measured over From date of randomization up to 42 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Precentage of participants |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is objective response rate (ORR) assessed by blinded independent central review in arm A, the nivolumab-plus-ipilimumab group. It is defined as the percentage of participants whose best overall response was a confirmed complete response (CR) or partial response (PR). The listed primary population comprises all participants randomized in a salvage setting to arm A by TMB-High status. The stated assessment period runs from randomization up to 42 months.
For solid tumors assessed using RECIST criteria, the registry describes complete response as disappearance of all target lesions, with any pathological lymph nodes reduced in short axis to less than 10 mm. Partial response is a decrease of at least 30% in the sum of target-lesion diameters from baseline. The endpoint description also gives RANO definitions: complete response includes disappearance of enhancing disease and specified stable or improved clinical and imaging features; partial response requires at least a 50% decrease in the sum of products of perpendicular diameters of measurable enhancing lesions, with additional conditions. These criteria show that response classification depends on prespecified imaging and clinical features, not simply on a change in one lesion.
Response rate is used to describe the proportion of participants meeting a defined response threshold. It can provide a concise measure of observed antitumor activity, while not by itself describing how long responses last or whether outcomes differ from another treatment. Duration of response is separately listed as a secondary outcome. The registry record does not report the primary response percentage or its 95% confidence interval.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies an objective response rate as the primary outcome, but does not report the primary outcome result. It names the endpoint, its population, assessment method, response definitions, and timeframe; it does not give the number or percentage of arm A participants with a confirmed complete or partial response. A 95% confidence interval is specified as the measure of dispersion, but its limits are not reported. Consequently, neither the estimated response rate nor its precision can be described from the registry record.
This absence is especially important for interpreting the randomized design. Participants were assigned to a combination arm or a nivolumab monotherapy arm, but the primary outcome is an estimate for arm A alone. A response rate in one arm is not itself an estimate of the difference between treatments. The secondary outcomes include ORR by BICR in arm B, as well as investigator-assessed response in the study and several duration, timing, and clinical-benefit measures. Their results are also not reported in the registry information available for this analysis. Therefore, no comparative result between the randomized strategies can be stated.
The registry's safety information reports counts of participants at risk and affected for serious and other adverse events, and deaths, in three listed groups. These figures describe recorded events by group, but the registry information does not provide the corresponding detailed event definitions, exposure periods, or an analysis comparing randomized treatments. The listed serious-event terms and percentages likewise do not establish whether an event was caused by treatment. They should be read as reported safety summaries, not as proof of causation or as direct measures of comparative risk.
In general, a confidence interval describes statistical uncertainty around an estimated quantity. A narrower interval indicates greater precision under the analysis assumptions, while a wider interval indicates less precision. Because the estimate and interval are absent, the uncertainty around the primary response rate cannot be assessed. The record does not report a hypothesis test, a p-value, an adjusted treatment contrast, or an inferential conclusion for the primary endpoint.
The trial's completed status does not fill in these missing result details. Nor does enrollment alone establish that the primary estimate is precise. No conclusions about the size of response, the relative performance of the arms, or the clinical importance of any effect can be drawn from the primary result information because that result is not reported in the registry record.
9. Statistical Methods Explained
What does the primary endpoint estimate?
The primary outcome is a proportion: the percentage of participants in arm A whose best overall response is confirmed complete response or partial response according to BICR. In general, a proportion translates an outcome classification into a share of the defined population. Its interpretation depends on the response criteria, the population included, and the period in which response is assessed. Here, the listed population is all participants randomized in a salvage setting to arm A by TMB-High status, and the timeframe is from randomization up to 42 months.
The registry specifies a 95% confidence interval for the response percentage. In general, a confidence interval communicates uncertainty associated with an estimate under the statistical method used. It does not show the range of outcomes for individual participants, nor does it guarantee that the true value lies within the interval. The primary estimate and interval are not reported in the registry record, so the endpoint's observed level and precision remain unknown.
Why distinguish a response estimate from a treatment comparison?
In general, an outcome estimate within one arm answers a descriptive question about that arm. A comparative treatment question requires an estimate that contrasts outcomes between treatment groups, with an analysis suited to the design and endpoint. Random allocation can support causal comparisons when the analysis uses the randomized groups appropriately, but randomization alone does not turn a single-arm endpoint result into a between-arm contrast.
Here the primary outcome is designated for arm A, while the study includes a randomized nivolumab-monotherapy arm. The registry lists an Arm B BICR response rate as a secondary outcome but does not report a primary contrast between arms or the corresponding results. Thus the named primary endpoint cannot establish whether response differs between the combination and monotherapy strategies. This distinction is about the question estimated, not a judgment about the study's design quality.
What does blinded independent review contribute?
The trial is open-label, meaning masking is recorded as none. The primary outcome is nevertheless assessed by blinded independent central review. In general, independent review can help apply response criteria consistently and reduce the influence of knowledge about assigned treatment when classifying images. These are general reasons for using blinded review; the registry record does not describe the review process, image handling, or quality-control procedures in this trial. The record also lists investigator-assessed response outcomes, allowing different assessment sources to be identified, but reports no results that would permit their estimates to be compared.
How should response criteria be understood?
Response criteria convert clinical and imaging observations into categories such as complete response and partial response. The registry includes RECIST definitions and also RANO definitions. In general, such criteria make an endpoint more reproducible by setting rules for how changes in measurable disease and other clinical features are classified. The registry does not explain how the two criteria sets were assigned across tumor types, or provide tumor-specific outcome results. Therefore, the endpoint definition can be described, but the record does not support an assessment of how response rates varied by criterion or tumor type.
What can planning illustrations tell readers?
In general, sample-size planning illustrations use assumptions about an effect, allocation, significance level, and statistical method to show how a future study might be designed to detect a specified effect. The assumptions recorded for the illustrations state a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; they define the target effect as a stated fraction of the observed effect. For time-to-event outcomes the illustrations use a total-event count, while other outcomes use participants per arm. These are planning conventions, not observed trial results or evidence of observed power.
The registry explicitly describes these illustrations as based on the observed effect, not the trial's own design. The record does not report the trial's sample-size justification or whether these planning assumptions formed part of its protocol. The values of the illustrations are not part of the result information, and they should not be mistaken for the study's actual enrollment or outcome estimates.
More broadly, statistical interpretation depends on the match between the endpoint, analysis population, and analysis method. The record identifies the primary population and the endpoint but does not report the statistical analysis plan, the handling of missing response assessments, or an analysis dataset. It would be inappropriate to fill in those methodological details by assuming common practice. The distinction between what the registry names and what it documents is essential: the recorded design establishes the study's stated framework, while absent analysis details limit evaluation of how that framework was implemented.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 14 outcome measures, including the primary BICR-assessed ORR in arm A and secondary measures of response, duration of response, time to response, and clinical benefit. Some secondary outcomes are assessed by investigators and others by BICR; an Arm B BICR-assessed ORR is also listed. The registry record lists 0 analysis records. It does not report a statistical analysis plan or a procedure for controlling multiplicity across the outcomes or assessments.
In general, multiplicity arises when several outcomes, comparisons, or repeated tests are considered. Without an appropriate plan, the chance of at least one apparently notable finding can increase. This is a general statistical concern, not a claim that any particular error occurred in this study. Because inferential results and a multiplicity strategy are not reported in the registry record, the intended hierarchy among the listed secondary outcomes and any adjustment to statistical tests cannot be determined.
Missing-data methods are not reported in the registry record. The primary endpoint describes a population of all participants randomized in a salvage setting to arm A by TMB-High status, but the record does not explain how participants without an evaluable response assessment, those who discontinue, or other missing endpoint information were handled. It also does not describe sensitivity analyses for missing outcomes.
Analysis populations beyond the stated primary population are not reported in the registry record. The record does not specify whether analyses followed randomized assignment, used a different evaluable population, or applied other population rules. These omissions limit assessment of potential bias and of whether the reported analysis, if available, would align with the randomized design. They do not justify assuming a particular approach.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm A: Nivolumab+Ipilimumab | 90 | 135 | 66.7% |
| Arm B: Nivolumab | 39 | 76 | 51.3% |
| Arm B: Nivolumab+Ipilimumab (Rollover) | 11 | 22 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A: Nivolumab+Ipilimumab | 97 of 136 |
| Arm B: Nivolumab | 42 of 76 |
| Arm B: Nivolumab+Ipilimumab (Rollover) | 20 of 22 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A: Nivolumab+Ipilimumab | 121 of 135 |
| Arm B: Nivolumab | 64 of 76 |
| Arm B: Nivolumab+Ipilimumab (Rollover) | 13 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A: Nivolumab+Ipilimumab | Arm B: Nivolumab | Arm B: Nivolumab+Ipilimumab (Rollover) |
|---|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 43 of 135 | 25 of 76 | 7 of 22 |
| Pyrexia | General disorders | 5 of 135 | 0 of 76 | 1 of 22 |
| Colitis | Gastrointestinal disorders | 4 of 135 | 0 of 76 | 1 of 22 |
| Pneumonia | Infections and infestations | 2 of 135 | 3 of 76 | 0 of 22 |
| Urinary tract infection | Infections and infestations | 3 of 135 | 1 of 76 | 1 of 22 |
| Diarrhoea | Gastrointestinal disorders | 3 of 135 | 1 of 76 | 0 of 22 |
| Fatigue | General disorders | 3 of 135 | 1 of 76 | 0 of 22 |
| Urosepsis | Infections and infestations | 2 of 135 | 0 of 76 | 2 of 22 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 135 | 1 of 76 | 1 of 22 |
| Anaemia | Blood and lymphatic system disorders | 1 of 135 | 2 of 76 | 0 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: Nivolumab+Ipilimumab | Arm B: Nivolumab | Arm B: Nivolumab+Ipilimumab (Rollover) |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 50 of 135 | 14 of 76 | 3 of 22 |
| Fatigue | General disorders | 41 of 135 | 17 of 76 | 2 of 22 |
| Pruritus | Skin and subcutaneous tissue disorders | 36 of 135 | 15 of 76 | 8 of 22 |
| Anaemia | Blood and lymphatic system disorders | 32 of 135 | 16 of 76 | 3 of 22 |
| Nausea | Gastrointestinal disorders | 19 of 135 | 15 of 76 | 4 of 22 |
| Decreased appetite | Metabolism and nutrition disorders | 28 of 135 | 6 of 76 | 2 of 22 |
| Constipation | Gastrointestinal disorders | 23 of 135 | 10 of 76 | 1 of 22 |
| Pyrexia | General disorders | 21 of 135 | 10 of 76 | 2 of 22 |
| Aspartate aminotransferase increased | Investigations | 20 of 135 | 12 of 76 | 1 of 22 |
| Rash | Skin and subcutaneous tissue disorders | 25 of 135 | 7 of 76 | 1 of 22 |
Serious events with the highest arm-level rate: malignant neoplasm progression (32.9%), urosepsis (9.1%), colitis (4.5%), gastric perforation (4.5%), nausea (4.5%).
The registry lists safety figures for three groups: Arm A nivolumab plus ipilimumab, Arm B nivolumab, and Arm B nivolumab plus ipilimumab (rollover). For each group, the record gives participants at risk and affected for serious adverse events and for other adverse events, as well as deaths. The listed serious-adverse-event figures are 135 at risk and 90 affected in Arm A, 76 at risk and 39 affected in Arm B nivolumab, and 22 at risk and 11 affected in the rollover group. The record lists deaths of 97, 42, and 20 in those respective groups.
Other-adverse-event figures are listed as 135 at risk and 121 affected in Arm A, 76 at risk and 64 affected in Arm B nivolumab, and 22 at risk and 13 affected in the rollover group. These are registry counts; they are not converted into rates or treatment comparisons. The record does not report exposure-adjusted rates or explain the observation period for these summaries.
The serious-event terms listed include malignant neoplasm progression (32.9%), urosepsis (9.1%), colitis (4.5%), gastric perforation (4.5%), nausea (4.5%), and malaise (4.5%). The denominator and event-count basis for these percentages are not reported in the registry record. The record also does not state that the listed events were caused by treatment. The figures should therefore be interpreted as descriptive safety information, not as causal or comparative estimates.
12. What the Result Does, and Does Not, Mean
The study's registry record establishes a randomized, open-label, phase 2 framework comparing nivolumab plus ipilimumab with nivolumab monotherapy in advanced or metastatic solid tumors with high tumor mutational burden. It also specifies a primary response endpoint for the combination arm, assessed by blinded independent central review, and gives the criteria used to define response. These details identify the clinical and statistical question the primary outcome was intended to address: the proportion of the specified arm A population with a confirmed complete or partial response during the stated assessment period.
However, the primary response percentage and its confidence interval are not reported in the registry record. As a result, the observed response level and its precision cannot be evaluated. The record also does not report a primary comparison between randomized arms. A trial can be randomized while a particular listed endpoint remains an estimate for one arm; the design label alone does not supply a treatment effect estimate.
The registry lists secondary outcomes that could address response in arm B and other aspects of response, including duration, timing, and clinical benefit, but their results are not reported in the information. There is consequently no basis to describe differences between the treatments, consistency across assessment methods, or the relationship between response and its duration.
The safety counts provide descriptive information for the named groups, but do not establish that events were attributable to treatment or permit a direct comparison of safety between the randomized strategies. Group-specific observation time, event definitions, and comparative analyses are not reported in the registry record. The rollover group is listed separately and should not be treated as one of the two named randomized treatment arms without further information.
In general, statistical evidence requires both an estimate and information about uncertainty, with an analysis appropriate to the question. Those elements are not available for the primary response endpoint in this record. The trial's completed status and enrollment figure do not substitute for missing outcome estimates. The record can therefore describe the intended evaluation and reported safety counts, but it does not support conclusions about the magnitude, precision, or comparative meaning of the primary efficacy outcome.
13. Why This Trial Matters Statistically
This trial raises an important statistical distinction between a randomized study and a comparative primary endpoint. The study is recorded as randomized between a combination strategy and nivolumab monotherapy, yet the primary outcome is the response rate for arm A alone. A within-arm estimate can describe observed response in that group; a treatment comparison requires an explicit contrast between groups. Keeping these questions separate helps prevent a response-rate endpoint from being interpreted as comparative evidence merely because randomization occurred.
The response outcome also illustrates why assessment methods matter. The study is open-label, while the primary response measure is determined by blinded independent central review. In general, blinded assessment can reduce the influence of treatment knowledge on outcome classification. The registry additionally lists investigator-assessed outcomes, but does not report their results or the procedures used to reconcile differing assessments. The distinction between assessment sources is therefore part of the study question, even though their relative findings cannot be evaluated.
The listed outcomes span response occurrence, response duration, time to response, and clinical benefit. These are related but not interchangeable quantities: in general, a response proportion does not describe how long responses last, and a duration measure does not by itself state how many participants responded. Multiple outcome types make clear definitions and an analysis plan important. Such a plan, including any approach to multiple testing, is not reported in the registry record.
Finally, the record shows how registry completeness affects statistical interpretation. Design and endpoint definitions are available, but primary efficacy estimates and their uncertainty are not. Without those results, the registry can identify the intended analysis but cannot support an evaluation of its magnitude or precision. This is a useful reminder to distinguish the question a study set out to address from the evidence available to answer it.
14. 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 principal limitation for interpreting efficacy is that the registry record does not report the primary ORR estimate or its 95% confidence interval. It also does not report the listed secondary outcome results. Without outcome estimates, precision measures, or comparative analyses, the clinical activity described as the study's purpose cannot be quantified from this record.
The primary endpoint is specific to arm A, rather than a stated contrast between the randomized treatment groups. The registry lists an Arm B BICR ORR as a secondary outcome, but does not provide its result or a direct treatment-effect estimate. This limits interpretation of the randomized comparison. The primary population is described as participants randomized in a salvage setting to arm A by TMB-High status, but additional population details are not reported.
Further methodological information is also absent. The registry record does not report the statistical analysis plan, the sample-size justification, missing-data procedures, analysis populations beyond the stated primary population, or a multiplicity strategy. It does not describe the BICR process, how response assessments were handled when incomplete, or the use of sensitivity analyses. These details cannot be inferred from the study being randomized or from the response criteria alone.
The listed safety figures have their own limitations. The record does not report exposure time or sufficient definitions to interpret the groups as comparable risk sets. It includes a rollover group as well as the two named randomized arms, and does not explain the rollover group's relationship to safety analyses. The basis for the percentages attached to serious-event terms is not reported. These factors preclude interpreting the figures as causal effects or as direct treatment comparisons.
Finally, the registry's completed status does not establish that all relevant results are available in this record. These limitations describe what the record does not report; they do not establish that the information was not collected elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Nivolumab Combined With Ipilimumab and Nivolumab Alone in Patients With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H) — NCT03668119.
- Registry record last updated 2024-08-28; status last verified 2024-07.
- Results first posted 2023-05-18.
- 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.
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18. Record Summary
The registry record describes NCT03668119, a completed, randomized, open-label, parallel-group phase 2 study of nivolumab plus ipilimumab versus nivolumab alone in advanced or metastatic solid tumors with high tumor mutational burden. Enrollment is recorded as 212. The primary outcome is BICR-assessed objective response rate in arm A, defined by confirmed complete or partial response, from randomization up to 42 months.
The record identifies a 95% confidence interval as the dispersion measure but does not report the primary estimate or interval. It lists secondary response, duration, timing, and clinical-benefit outcomes, without results in the record. Safety counts are listed for the two named arms and a rollover group. The statistical analysis plan, missing-data methods, multiplicity approach, sample-size justification, and a comparative primary analysis are not reported in the registry record.