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 An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors (NCT02488759), a randomized phase 1, phase 2 study. The primary outcome is Metastatic: Investigator-Assessed Objective Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02488759 |
| Phase | Phase 1, Phase 2 |
| Condition | Various Advanced Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 578 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
The primary endpoint population is all treated participants in the metastatic cohorts. The record describes advanced cancers associated with viruses, including EBV-positive gastric cancer, HPV-positive squamous cell carcinoma of the head and neck, other anogenital HPV-associated cancers, gynecologic cancers, Merkel cell carcinoma, and nasopharyngeal carcinoma. The broader study also included a neoadjuvant cohort.
Intervention
The study evaluated nivolumab monotherapy and combinations with ipilimumab, relatlimab, or daratumumab, as well as nivolumab in a neoadjuvant cohort. The record lists intravenous infusions for the cohort descriptions. It does not report outcome results separately by each named combination in the information available for this analysis.
Comparator
The registry describes the study as non-comparative, open-label, and organized into multiple cohorts. Although the allocation field says randomized, the registry record does not specify a single control treatment or provide a comparative primary endpoint analysis. The cohort design should therefore not be read as a direct head-to-head test of all listed regimens.
Primary question
Among treated participants in the metastatic cohorts, what percentage had a confirmed complete or partial response according to RECIST 1.1, as assessed by investigators? The registry defines an objective response rate above 10% as of clinical interest and 25% or greater as of strong clinical interest. Those are prespecified interpretation thresholds in the endpoint description, not reported response results.
3. Trial Design
This was a phase 1/2, multiple-cohort study of nivolumab alone and nivolumab combinations in participants with virus-positive and virus-negative solid tumors. The registry describes the design as non-comparative, open-label, and parallel, while its allocation field is recorded as randomized. It does not explain the randomization process, how any randomized assignments related to the cohorts, or whether a specific treatment comparison was planned. Those details are not reported in the registry record.
The listed interventions were nivolumab, ipilimumab, relatlimab, and daratumumab. Cohort descriptions include metastatic monotherapy, nivolumab with ipilimumab, nivolumab with relatlimab, nivolumab with daratumumab, and a neoadjuvant cohort. The registry also notes that enrollment was closed for the relatlimab and daratumumab cohorts. Country participation varied by cohort, as recorded in the registry, so the cohorts did not necessarily have identical geographic participation.
The registry lists enrollment as 578 and the study status as completed. The recorded study start was 2015-10-13, and primary completion was 2021-03-19. The primary endpoint population was all treated participants in the metastatic cohorts; this is distinct from assuming that every participant in the overall enrollment entry contributed to that endpoint.
The primary outcome was investigator-assessed objective response rate in metastatic cohorts. Secondary metastatic outcomes were investigator-assessed duration of response, overall survival, and investigator-assessed progression-free survival. The registry record lists eight outcome measures, but detailed numerical outcome results are not available in the information. It lists zero analyses. The protocol, analysis plan, detailed allocation procedures, and sample-size justification are not reported in the registry 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: 578 participants treated
Overall Study
| Stage | Metastatic Monotherapy | Metastatic Combo A | Metastatic Combo B | Metastatic Combo C | Metastatic Combo D | Neoadjuvant |
|---|---|---|---|---|---|---|
| STARTED | 113 | 195 | 133 | 8 | 6 | 123 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 116 |
| NOT COMPLETED | 113 | 195 | 133 | 8 | 6 | 7 |
Reasons for not completing this period:
| Reason | Metastatic Monotherapy | Metastatic Combo A | Metastatic Combo B | Metastatic Combo C | Metastatic Combo D | Neoadjuvant |
|---|---|---|---|---|---|---|
| Disease progression | 73 | 111 | 62 | 7 | 4 | 2 |
| Study drug toxicity | 11 | 33 | 31 | 0 | 0 | 2 |
| Adverse event unrelated to study drug | 9 | 11 | 7 | 0 | 1 | 0 |
| Participant request to discontinue study treatment | 6 | 8 | 4 | 0 | 0 | 0 |
| Withdrawal by Subject | 4 | 0 | 3 | 0 | 0 | 2 |
| Lost to Follow-up | 0 | 0 | 2 | 0 | 0 | 0 |
| Maximum clinical benefit | 3 | 0 | 1 | 0 | 0 | 0 |
| Other reasons | 7 | 32 | 23 | 1 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: All treated participants in the neoadjuvant cohort
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 7 groups are shown.
| Characteristic | Unit | Metastatic Monotherapy | Metastatic Combo A | Metastatic Combo B | Metastatic Combo C | Metastatic Combo D | Neoadjuvant |
|---|---|---|---|---|---|---|---|
| Participants analysed | 113 | 195 | 133 | 8 | 6 | 123 | |
| Age, Continuous | Years | 57.4 (SD 13.5) | 57.5 (SD 13.2) | 48.2 (SD 12.3) | 59.0 (SD 7.6) | 66.5 (SD 15.3) | 62.0 (SD 12.7) |
| Sex: Female, Male: Female | Participants | 39 | 85 | 129 | 1 | 3 | 59 |
| Sex: Female, Male: Male | Participants | 74 | 110 | 4 | 7 | 3 | 64 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 2 | 0 | 2 | 0 | 0 | 2 |
| Race (NIH/OMB): Asian | Participants | 14 | 31 | 10 | 0 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 6 | 5 | 0 | 0 | 3 |
| Race (NIH/OMB): White | Participants | 86 | 147 | 115 | 8 | 6 | 113 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 8 | 11 | 1 | 0 | 0 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Metastatic: Investigator-Assessed Objective Response Rate (ORR), measured over From the date of first dose to the date of the initial objectively documented tumor progression or the date of the last tumor assessment prior to subsequent therapy (Up to 65 months).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is investigator-assessed objective response rate, or ORR, among all treated participants in the metastatic cohorts. It is the percentage with a best overall response of confirmed complete response or partial response using RECIST 1.1 criteria. A complete response requires disappearance of target lesions, with pathological lymph nodes reduced to a short axis under 10 mm. A partial response requires at least a 30% decrease in the sum of target-lesion diameters relative to baseline.
ORR is a binary-outcome summary: each participant is classified according to whether a confirmed complete or partial response was recorded, and the endpoint expresses the share meeting that definition. As a general statistical concept, this measure gives a concise description of observed tumor response under the specified assessment rules. It does not by itself describe how long a response lasts, how long participants remain alive, or how long progression is delayed; those questions are addressed by the listed secondary outcomes of duration of response, overall survival, and progression-free survival.
The registry states that an ORR above 10% would be of clinical interest and an ORR of 25% or greater would be of strong clinical interest. These thresholds are interpretive criteria in the endpoint description. A numerical ORR and its 95% confidence interval are not reported in the registry record, so the thresholds cannot be compared with an observed estimate from the information available.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies investigator-assessed ORR as the primary endpoint for treated participants in the metastatic cohorts, but it does not report the numerical ORR, its confidence interval, or the cohort-level response counts. Consequently, the posted information does not establish where an observed estimate lies relative to the registry's clinical-interest thresholds of above 10% and 25% or greater. Those thresholds describe how an ORR would be interpreted; they are not trial findings.
The endpoint definition is specific: a participant must have a confirmed complete or partial response under RECIST 1.1. A complete response concerns disappearance of target lesions and the stated lymph-node criterion. A partial response requires the stated reduction in the sum of target-lesion diameters from baseline. The endpoint therefore reflects tumor assessments under those rules, not a general judgment about a participant's overall health or subsequent clinical course.
The registry calls the study non-comparative, despite recording randomized allocation. In the absence of a reported control group analysis or specified treatment contrast, these cohort data should not be interpreted as a direct estimate of the relative effect of nivolumab versus another treatment. Nor can results from separate regimens be ranked from the available record: numerical endpoint results by cohort are not reported in the information available for this analysis.
The registry lists 578 for enrollment, but the primary analysis population is defined as all treated participants in the metastatic cohorts. Those labels do not establish that the same participants are represented in every outcome. Cohort-specific numbers treated and numbers assessed for ORR are not reported in the registry record. The record also does not provide details about participants without an assessable response, the handling of missing tumor assessments, or the number of participants contributing to a confidence interval.
As a general statistical point, a confidence interval describes uncertainty around an estimated response percentage under the assumptions of the analysis. A wider interval indicates less precision, while a narrower interval indicates greater precision; neither feature alone establishes clinical importance. The registry specifies a 95% confidence interval as the endpoint's dispersion measure, but the numerical interval and its calculation method are not reported. With no estimate or interval, the direction and precision of the primary endpoint cannot be assessed.
The listed secondary outcomes—duration of response, overall survival, and progression-free survival—address different aspects of outcome and require their own definitions, analysis populations, and follow-up information. Their names alone do not provide evidence about their results. Numerical results and detailed methods for those outcomes are not reported in the registry record. Overall, the available record supports describing the study question and endpoint definitions, but not drawing a conclusion about the observed response rate or differences between regimens.
9. Statistical Methods Explained
The primary outcome is a binary response measure summarized as a percentage of participants. Each participant is classified by best overall response: a confirmed complete response or partial response meets the ORR definition, while other response categories do not meet that definition. The registry gives the assessment criteria but does not report the response counts or numerical percentage. It identifies a 95% confidence interval as the measure of dispersion, while the specific interval calculation method is not reported in the registry record.
What does the confidence interval convey?
As a general statistical explanation, a confidence interval expresses the uncertainty associated with an estimated quantity, based on a specified method and its assumptions. It is not a range containing a fixed proportion of individual participant responses. For a response percentage, the estimate summarizes the observed proportion, while the interval helps readers judge how precisely that proportion has been estimated. The interval's interpretation depends on the analysis method and on the data included.
The registry names the 95% confidence interval but gives no numerical interval in the information. It also does not identify the interval method. Therefore, no assessment of interval width, precision, or compatibility with the stated clinical-interest thresholds can be made. In general, a point estimate near a threshold with a broad interval may leave substantial uncertainty about the underlying response percentage. That is a general consideration, not a finding about this study's unreported estimate.
How should the response definition be read?
RECIST 1.1 supplies the tumor-response framework used in the endpoint. The registry defines complete response through disappearance of target lesions and a criterion for pathological lymph nodes. It defines partial response through a reduction in the sum of target-lesion diameters from baseline. Requiring confirmation makes the outcome definition more specific than counting any single assessment that appears favorable. The registry does not report the timing or frequency of tumor assessments, the confirmation rules in further detail, or how missing or unevaluable assessments were handled.
The endpoint timeframe is described as beginning at the date of first dose and continuing to initial objectively documented tumor progression or the last tumor assessment before subsequent therapy, up to 65 months. This is the registry's stated timeframe; it does not mean every participant had the same duration of observation. The actual follow-up distribution and the number assessed at different times are not reported in the registry record.
What does the study structure imply for analysis?
The study is described as non-comparative, open-label, and multiple-cohort, with parallel model and randomized allocation recorded in the registry. These terms do not, by themselves, specify a statistical comparison. In a non-comparative study, a cohort's response percentage can be described against an external interpretive threshold, but that is different from a randomized treatment-effect contrast. The record does not explain the allocation procedure, identify a primary between-group contrast, or state how the randomized allocation was used analytically.
The primary endpoint population is listed as all treated participants in the metastatic cohorts. That description should not be substituted with the overall enrollment entry or interpreted as a full account of analysis eligibility. The registry does not report cohort-specific treated counts for the endpoint, response-evaluable counts, or a detailed analysis population definition. It also does not describe a missing-data strategy, sensitivity analyses, adjustment for prognostic factors, or handling of participants who began subsequent therapy before a final assessment.
How should planning illustrations be understood?
Any sample-size illustrations associated with these results are planning calculations, not evidence that the study achieved a particular probability of detecting an effect. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The instructions for those illustrations distinguish participants per arm for ordinary outcomes from total events for time-to-event outcomes.
As a general statistical point, such calculations explore how a future study might be sized under chosen assumptions. They do not describe the actual design rationale unless the trial's own design documentation says so, and they are not observed power. The registry record does not report the trial's sample-size justification or a numerical observed effect for the primary endpoint in the information. Therefore, no trial-specific planning result or recalculated estimate can be stated. Sample-size illustrations should not be read as a substitute for the missing endpoint estimate, its confidence interval, or a prespecified analysis plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple cohorts, several interventions, and eight outcome measures. It identifies metastatic investigator-assessed ORR as the primary outcome and lists duration of response, overall survival, and progression-free survival as secondary outcomes. It does not report a multiplicity strategy describing whether or how statistical error was controlled across outcomes, cohorts, or treatment combinations. The number of analyses recorded is zero. The statistical analysis plan and any prespecified hierarchy for interpreting results are not reported in the registry record.
Multiplicity matters generally when many outcomes or groups are examined: the chance of observing an apparently notable result can increase when numerous analyses are considered. That general concern does not establish that any particular result from this study is spurious. With no numerical outcome results or analysis details in the information available, the scale and handling of multiplicity cannot be evaluated.
Missing-data handling is also not reported in the registry record. The endpoint population is described as all treated participants in the metastatic cohorts, but the record does not state how participants without a post-baseline tumor assessment, those with unevaluable scans, or those who began subsequent therapy were treated in the ORR calculation. Cohort-specific denominators and response-evaluable counts are not reported. The endpoint timeframe references the last tumor assessment before subsequent therapy, but that wording does not specify a missing-data rule.
The registry does not provide enough information to determine whether the analysis used an intention-to-treat, per-protocol, or other named population. It specifies all treated metastatic participants for the primary outcome, which is the population description that can be reported. The analysis population for secondary outcomes, censoring rules, and sensitivity analyses are not reported in the registry record.
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 |
|---|---|---|---|
| Metastatic Monotherapy | 59 | 113 | 52.2% |
| Metastatic Combo A | 130 | 195 | 66.7% |
| Metastatic Combo B | 99 | 133 | 74.4% |
| Metastatic Combo C | 5 | 8 | 62.5% |
| Metastatic Combo D | 5 | 6 | 83.3% |
| Neoadjuvant | 40 | 123 | 32.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Metastatic Monotherapy | 82 of 113 |
| Metastatic Combo A | 133 of 195 |
| Metastatic Combo B | 86 of 133 |
| Metastatic Combo C | 7 of 8 |
| Metastatic Combo D | 5 of 6 |
| Neoadjuvant | 40 of 123 |
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 |
|---|---|
| Metastatic Monotherapy | 110 of 113 |
| Metastatic Combo A | 189 of 195 |
| Metastatic Combo B | 129 of 133 |
| Metastatic Combo C | 7 of 8 |
| Metastatic Combo D | 5 of 6 |
| Neoadjuvant | 108 of 123 |
Most frequent serious adverse event terms
| Event term | Organ system | Metastatic Monotherapy | Metastatic Combo A | Metastatic Combo B | Metastatic Combo C | Metastatic Combo D | Neoadjuvant |
|---|---|---|---|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 24 of 113 | 39 of 195 | 21 of 133 | 2 of 8 | 3 of 6 | 2 of 123 |
| Urinary tract infection | Infections and infestations | 3 of 113 | 11 of 195 | 7 of 133 | 0 of 8 | 0 of 6 | 0 of 123 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 4 of 113 | 7 of 195 | 10 of 133 | 0 of 8 | 0 of 6 | 0 of 123 |
| Pyrexia | General disorders | 3 of 113 | 5 of 195 | 7 of 133 | 0 of 8 | 0 of 6 | 2 of 123 |
| Colitis | Gastrointestinal disorders | 1 of 113 | 3 of 195 | 11 of 133 | 0 of 8 | 0 of 6 | 1 of 123 |
| Diarrhoea | Gastrointestinal disorders | 1 of 113 | 9 of 195 | 4 of 133 | 0 of 8 | 0 of 6 | 2 of 123 |
| Acute kidney injury | Renal and urinary disorders | 2 of 113 | 5 of 195 | 8 of 133 | 0 of 8 | 0 of 6 | 0 of 123 |
| Sepsis | Infections and infestations | 3 of 113 | 6 of 195 | 4 of 133 | 0 of 8 | 0 of 6 | 1 of 123 |
| Dehydration | Metabolism and nutrition disorders | 1 of 113 | 4 of 195 | 2 of 133 | 0 of 8 | 0 of 6 | 3 of 123 |
| Anaemia | Blood and lymphatic system disorders | 1 of 113 | 1 of 195 | 5 of 133 | 0 of 8 | 0 of 6 | 1 of 123 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Metastatic Monotherapy | Metastatic Combo A | Metastatic Combo B | Metastatic Combo C | Metastatic Combo D | Neoadjuvant |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 47 of 113 | 81 of 195 | 46 of 133 | 6 of 8 | 1 of 6 | 40 of 123 |
| Diarrhoea | Gastrointestinal disorders | 31 of 113 | 61 of 195 | 54 of 133 | 1 of 8 | 2 of 6 | 22 of 123 |
| Nausea | Gastrointestinal disorders | 25 of 113 | 45 of 195 | 48 of 133 | 2 of 8 | 3 of 6 | 42 of 123 |
| Anaemia | Blood and lymphatic system disorders | 28 of 113 | 53 of 195 | 42 of 133 | 2 of 8 | 2 of 6 | 11 of 123 |
| Constipation | Gastrointestinal disorders | 27 of 113 | 51 of 195 | 37 of 133 | 1 of 8 | 0 of 6 | 21 of 123 |
| Pruritus | Skin and subcutaneous tissue disorders | 23 of 113 | 60 of 195 | 35 of 133 | 0 of 8 | 1 of 6 | 11 of 123 |
| Decreased appetite | Metabolism and nutrition disorders | 24 of 113 | 48 of 195 | 32 of 133 | 2 of 8 | 1 of 6 | 15 of 123 |
| Cough | Respiratory, thoracic and mediastinal disorders | 26 of 113 | 49 of 195 | 17 of 133 | 2 of 8 | 1 of 6 | 7 of 123 |
| Vomiting | Gastrointestinal disorders | 21 of 113 | 31 of 195 | 33 of 133 | 1 of 8 | 0 of 6 | 14 of 123 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 24 of 113 | 35 of 195 | 26 of 133 | 2 of 8 | 1 of 6 | 10 of 123 |
Serious events with the highest arm-level rate: malignant neoplasm progression (50.0%), dyspnoea (25.0%), large intestine infection (16.7%), pneumonia (16.7%), respiratory tract infection (16.7%).
The registry reports safety counts separately for metastatic monotherapy, metastatic combination groups A through D, and neoadjuvant participants. For each group, it lists participants at risk and affected for serious events and for other events, along with a death count. These are counts, not rates, and the registry information does not define all the safety fields or provide exposure-adjusted measures. The group counts should therefore be read as registry-reported descriptive figures rather than as direct comparisons of risk across regimens.
The serious-event affected counts are 59 in metastatic monotherapy, 130 in metastatic combination A, 99 in metastatic combination B, 5 in metastatic combination C, 5 in metastatic combination D, and 40 in neoadjuvant. The corresponding at-risk counts are listed as 113, 195, 133, 8, 6, and 123. Death counts are listed separately as 82, 133, 86, 7, 5, and 40, respectively. The registry does not provide the cause, timing, or relationship to treatment for these deaths in the information.
The record lists malignant neoplasm progression at 50.0%, dyspnoea at 25.0%, and large intestine infection, pneumonia, respiratory tract infection, and tumour obstruction at 16.7% each among the top serious terms. The denominator and selection method for these percentages are not reported in the registry record. These figures do not establish treatment causality or allow comparison of event frequency between groups.
12. What the Result Does, and Does Not, Mean
The record establishes the study's intended question and the criteria used to define its primary endpoint. It describes a metastatic ORR assessment based on confirmed complete or partial response under RECIST 1.1, specifies all treated participants in metastatic cohorts as the endpoint population, and gives clinical-interest thresholds of above 10% and 25% or greater. It also identifies the secondary outcomes and records safety counts by study group.
However, the numerical primary endpoint result and its 95% confidence interval are not reported in the registry information available for this analysis. Therefore, the observed response percentage, its precision, and its relation to the stated thresholds cannot be described. The record does not provide numerical results for the listed secondary outcomes either. Endpoint definitions and thresholds are not substitutes for observed outcome data.
The study's non-comparative description is important for interpretation. The record does not present a specific control group or a primary treatment contrast. The fact that randomized allocation is recorded does not supply the missing details about allocation or establish a comparative estimate. Without reported analysis results and methods, the available information cannot support ranking the combinations or attributing differences to one regimen.
Safety counts are descriptive entries and should not be treated as comparative risks. The group sizes differ, exposure time and event definitions are not available in the information presented, and the denominator for the listed serious-event term percentages is not reported. Counts of deaths are listed, but cause and treatment relationship are not specified.
In general, clinical interpretation benefits from an effect estimate, a measure of precision, a clearly defined analysis population, and enough methodological detail to understand how observations were handled. Those elements are incomplete for the primary outcome in the registry record. The appropriate conclusion is limited: the record describes a multi-cohort investigation and its endpoint definitions, but the posted information does not establish the magnitude or precision of the primary response outcome.
13. Why This Trial Matters Statistically
This study illustrates a recurring statistical challenge in multi-cohort oncology research: a single registry entry can encompass different tumor types, treatment regimens, and treatment settings. The primary endpoint is restricted to treated participants in the metastatic cohorts, while the study also includes a neoadjuvant cohort. A summary enrollment entry does not replace cohort-specific denominators or outcome results when interpreting a particular endpoint.
It also shows why design labels need to be read together. The registry calls the study non-comparative and open-label, while recording randomized allocation and a parallel model. Those terms alone do not tell readers what was randomized, whether groups were intended for direct comparison, or which contrast would answer a treatment-effect question. Statistical interpretation depends on the actual allocation and analysis plan, details that are not reported in the registry record.
The response endpoint makes the choice of outcome definition consequential. ORR is built from confirmed RECIST 1.1 classifications, with explicit criteria for complete and partial response. A defined endpoint improves clarity about what is counted, but it does not by itself communicate the observed rate, its uncertainty, or how incomplete assessments were handled. The absent numerical ORR and confidence interval are therefore central limits on interpretation.
Finally, the safety record demonstrates the difference between counts and comparative evidence. Counts across groups do not automatically account for unequal group sizes, follow-up, or exposure, and the top serious terms do not include a reported denominator. Clear outcome definitions and complete analysis reporting are necessary to distinguish a descriptive registry entry from evidence about comparative effects or risks.
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 main limitation is that the registry information available for analysis does not include a numerical primary ORR or its 95% confidence interval. It therefore does not allow assessment of the endpoint's magnitude or precision, or comparison with the registry's stated clinical-interest thresholds. Numerical findings for the secondary outcomes are also not reported in the information.
The study includes multiple cohorts and treatment combinations, but the record does not provide cohort-specific endpoint results or detailed numbers assessed for response. The primary population is stated as all treated participants in metastatic cohorts, while the overall enrollment entry is 578; the record does not show how many participants in each metastatic cohort contributed to ORR. It also does not explain how unevaluable or missing tumor assessments were handled.
Design and analysis details are limited. Randomized allocation is recorded alongside a non-comparative, open-label description, but the randomization process, treatment contrasts, analysis plan, multiplicity procedures, and sample-size justification are not reported in the registry record. The available details do not support an inference of comparative treatment effects.
Safety reporting is also descriptive. The registry lists at-risk and affected counts and deaths by group, but the information available does not specify all field definitions, exposure time, event attribution, or the denominator underlying the serious-term percentages. The record does not state whether listed deaths were caused by disease, treatment, or other factors. These omissions limit comparisons across groups and interpretation of the safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Investigational Immuno-therapy Study to Investigate the Safety and Effectiveness of Nivolumab, and Nivolumab Combination Therapy in Virus-associated Tumors — NCT02488759.
- Registry record last updated 2023-11-13; status last verified 2023-11.
- Results first posted 2022-04-12.
- 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 a completed phase 1/2, open-label, non-comparative, multiple-cohort study of nivolumab monotherapy and combination therapy in solid tumors. It lists randomized allocation, a parallel model, enrollment of 578, and study dates from 2015-10-13 to primary completion on 2021-03-19.
The primary outcome is investigator-assessed ORR in treated participants in metastatic cohorts, defined by confirmed complete or partial response under RECIST 1.1. The registry states clinical-interest thresholds but does not report the numerical ORR or confidence interval in the information available for this analysis. Secondary outcomes include duration of response, overall survival, and progression-free survival.
Safety counts are reported by metastatic and neoadjuvant groups. Detailed analysis methods, missing-data handling, multiplicity procedures, and cohort-specific primary results are not reported in the registry record.