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 MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies (NCT00441337), a non-randomized phase 1 study. The primary outcome is Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00441337 |
| Phase | Phase 1 |
| Condition | Carcinoma, Non-Small-Cell Lung, Colorectal Cancer, Malignant Melanoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 39 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced non-small cell lung cancer, colorectal cancer, malignant melanoma, clear cell renal cell cancer, or hormone refractory prostate cancer. The registry lists 39 participants enrolled. The safety population included participants who received at least one dose or any partial dose of nivolumab.
Intervention
MDX-1106, identified in the arm descriptions as nivolumab, given by intravenous infusion at one of four dose levels: 0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg. The descriptions say that, if criteria were met, two additional doses could be administered, one every 4 weeks.
Comparator
There was no randomized control group. This was a non-randomized, single-group study with dose-level cohorts, not a like-for-like comparison of treatment against control.
Primary question
The primary outcome counted participants with specified safety events, including severe adverse events, serious adverse events, drug-related adverse events, deaths, discontinuation due to an adverse event, dose-limiting toxicity, and immune-related adverse events. The registry also lists efficacy and pharmacokinetic aims, but posted numerical results for those outcomes are not reported in the registry record.
The central statistical question is descriptive: what safety events were recorded among participants at the listed dose levels during the stated observation period? The primary outcome is expressed as participant counts, and the posted adverse-event figures show the number at risk and the number affected for serious events and other adverse events. These figures can describe what was observed in this study, but they do not by themselves estimate how outcomes would differ under another treatment or no treatment.
The study included several malignancy types and four dose cohorts. That breadth is relevant to understanding the study’s early-phase, safety-focused purpose, but it also means the record does not establish a single disease-specific treatment effect. The posted record does not report comparative estimates, uncertainty intervals, or a statistical analysis of differences between dose cohorts. The question answered is therefore limited to describing the design, endpoint, and reported event counts, while identifying what remains unknown.
3. Trial Design
This was a phase 1, open-label, non-randomized, single-group dose-escalation study. The registry reports an enrollment of 39 and lists five condition categories: non-small-cell lung carcinoma, colorectal cancer, malignant melanoma, renal cancer, and prostate cancer. The brief summary specifies advanced non-small cell lung cancer, colorectal cancer, malignant melanoma, clear cell renal cell cancer, or hormone refractory prostate cancer.
Participants received MDX-1106, also identified in the arm descriptions as nivolumab, at one of four intravenous dose levels: 0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg. The arm descriptions state that a single infusion was administered and that, if criteria were met, two additional doses could be given, one every 4 weeks. The registry record does not report the criteria governing additional doses. The posted adverse-event groups list 6 participants at risk in each of the 0.3 mg/kg, 1 mg/kg, and 3 mg/kg groups, and 21 in the 10 mg/kg group.
There was no masking, and allocation was non-randomized. The dose groups should not be treated as randomized arms or as comparable control groups. Differences in their observed event counts could reflect factors other than dose, and the registry record does not report an adjusted comparison between them. The study began in 2006-08, reached primary completion in 2009-11, and is marked completed.
The listed aims included safety, tolerability, efficacy, and pharmacokinetics. Secondary outcomes covered response categories, disease control, response timing and duration, tumor progression, prostate-specific antigen measures, and selected electrocardiogram and blood-pressure measures. The registry record does not report a sample-size justification, detailed dose-escalation rules, or the statistical plan. These design details should not be inferred from the study’s phase or its dose levels.
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: 39 participants were enrolled and 39 were treated with at least 1 dose or a partial dose of study drug.
Overall Study
| Stage | 0.3 mg/kg Nivolumab | 1 mg/kg Nivolumab | 3 mg/kg Nivolumab | 10 mg/kg Nivolumab |
|---|---|---|---|---|
| STARTED | 6 | 6 | 6 | 21 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 6 | 6 | 21 |
Reasons for not completing this period:
| Reason | 0.3 mg/kg Nivolumab | 1 mg/kg Nivolumab | 3 mg/kg Nivolumab | 10 mg/kg Nivolumab |
|---|---|---|---|---|
| Disease Progression | 6 | 6 | 4 | 18 |
| Lost to Follow-up | 0 | 0 | 0 | 1 |
| Sponsor Decision | 0 | 0 | 1 | 2 |
| Did not meet inclusion criteria | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Population: All participants who received at least 1 dose or any partial dose of nivolumab were analyzed.
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: All participants who received at least 1 dose or any partial dose of study drug.
| Characteristic | Unit | 0.3 mg/kg Nivolumab | 1 mg/kg Nivolumab | 3 mg/kg Nivolumab | 10 mg/kg Nivolumab | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 6 | 6 | 6 | 21 | 39 | |
| Age, Continuous | years | 56.5 (SD 5.7) | 68.3 (SD 9.4) | 61.0 (SD 10.4) | 63.2 (SD 10.0) | 62.6 (SD 9.7) |
| Sex: Female, Male: Female | Participants | 2 | 3 | 2 | 10 | 17 |
| Sex: Female, Male: Male | Participants | 4 | 3 | 4 | 11 | 22 |
| Race/Ethnicity, Customized: White | participants | 4 | 3 | 4 | 18 | 29 |
| Race/Ethnicity, Customized: Black | participants | 2 | 3 | 2 | 3 | 10 |
| Region of Enrollment: United States | participants | 6 | 6 | 6 | 21 | 39 |
| Body Weight in kilograms (kg) | kg | 96.8 (88 to 136) | 73.9 (62 to 80) | 81.9 (55 to 98) | 81.3 (56 to 118) | 81.3 (55 to 136) |
| Time since initial diagnosis (years) | Years | 3.7 (1.4 to 6.8) | 2.7 (1.5 to 14.0) | 5.6 (0.7 to 11.4) | 4.1 (1.0 to 19.8) | 3.8 (0.7 to 19.8) |
| Type of Malignancy: Prostate Cancer | participants | 0 | 1 | 2 | 5 | 8 |
| Type of Malignancy: Melanoma | participants | 0 | 2 | 0 | 8 | 10 |
| Type of Malignancy: Non-small cell lung cancer | participants | 1 | 1 | 2 | 2 | 6 |
| Type of Malignancy: Renal cell cancer | participants | 0 | 0 | 0 | 1 | 1 |
| Type of Malignancy: Colorectal cancer | participants | 5 | 2 | 2 | 5 | 14 |
| Stage of Malignancy at Screening Diagnosis: Stage I | participants | 0 | 0 | 0 | 0 | 0 |
| Stage of Malignancy at Screening Diagnosis: Stage II | participants | 0 | 0 | 0 | 0 | 0 |
| Stage of Malignancy at Screening Diagnosis: Stage III | participants | 1 | 0 | 0 | 0 | 1 |
| Stage of Malignancy at Screening Diagnosis: Stage IV | participants | 5 | 6 | 6 | 21 | 38 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population, measured over Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is a set of participant counts for safety events in the safety population. Its title names severe adverse events, serious adverse events, drug-related adverse events, deaths, discontinuation of study drug due to an adverse event, dose-limiting toxicity, and immune-related adverse events. It is not a single clinical efficacy measure. The registry defines the safety population as participants who received at least one dose or any partial dose of nivolumab.
The observation window is Day 1 to 70 days post last dose of study drug, with an additional period of 28 days past study discontinuation. The registry defines adverse events broadly as new unfavorable symptoms, signs, or diseases, or worsening of a pre-existing condition, whether or not they are causally related to treatment. Serious adverse events are events meeting specified seriousness criteria, including death, life-threatening events, certain important medical events, or events requiring or prolonging hospitalization.
Counting participants with events is useful in an early-phase safety study because it gives a direct description of how many people experienced an event under the registry’s definitions. It is distinct from counting the total number of event episodes: one participant may experience more than one event, and the posted participant counts do not describe event frequency per person or event duration. The record also distinguishes severe events, defined as Grade 3 or 4, from serious events, which are classified using seriousness criteria and are not interchangeable with severity grades.
These counts help characterize observed safety experience, but they do not establish that the study drug caused an event. The registry’s drug-related category depends on the recorded relationship assessment, and the record’s definition includes certain, probable, possible, or missing relationship. The primary endpoint does not, on its own, quantify comparative risk because this study had no randomized control group.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures are descriptive counts within four non-randomized dose cohorts. For serious adverse events, the registry lists 3 of 6 participants at 0.3 mg/kg, 5 of 6 at 1 mg/kg, 4 of 6 at 3 mg/kg, and 11 of 21 at 10 mg/kg. For other adverse events, it lists 6 of 6, 6 of 6, 6 of 6, and 21 of 21, respectively. These are the figures to read from the posted results; they are not estimates from a randomized treatment comparison.
The serious-event figures show that participants in each listed cohort were recorded as having serious adverse events. They do not identify whether these events were caused by nivolumab. Nor do they establish a dose-response relationship. The groups were not randomized, and the registry record does not report an adjusted statistical comparison or uncertainty intervals for between-cohort differences. The observed counts therefore support a descriptive account, not a claim that one dose caused more or fewer events than another.
The registry lists malignant neoplasm progression as a top serious-event term at 66.7%, with anaemia at 33.3%, and anorexia, back pain, abdominal pain upper, and renal failure each at 16.7%. These percentages are reported terms, not mutually exclusive categories in the record. They should not be added together or interpreted as a distribution of all participants. The registry does not supply further detail about event timing, recurrence, severity by term, or attribution for each listed event.
The death figures are not reported in the registry record. A missing death count should not be read as zero. Similarly, the registry entries do not give numerical results for the other named primary safety categories, including drug-related events, discontinuations due to adverse events, dose-limiting toxicities, or immune-related adverse events. The primary outcome title alone does not establish how many participants experienced each of those outcomes.
The study’s stated aims also included efficacy and pharmacokinetics, and the secondary-outcome list names response and disease-control measures. However, numerical results for those measures are not reported in the registry record. No conclusion about tumor response or comparative efficacy can be drawn from the safety counts. The posted record also lists zero analyses, so no inferential analysis is reported. The sample-size section elsewhere on the page is a planning illustration based on an observed effect; it is not observed power and does not replace the study’s missing analysis results.
Overall, the record documents adverse-event counts in a small, early-phase study with mixed malignancy types and unequal cohort sizes. Those data are useful for describing the recorded safety experience, but the precision and interpretability of comparisons are limited. Without a control group, reported uncertainty estimates, complete outcome results, and a reported analysis plan, the figures cannot establish comparative effects or a causal treatment effect.
9. Statistical Methods Explained
The registry’s primary endpoint is based on counts of participants with specified events. This is a binary-outcome structure at the participant level: for each event category, a participant is counted as having experienced it or not having experienced it during the stated observation window. That framing differs from counting every event episode. A participant with repeated episodes may still contribute one participant to a count for that category, depending on the outcome definition. The record does not provide episode-level counts.
What a participant count describes
A count such as 3 of 6 describes the number of participants recorded with an event and the number at risk in that cohort. It is a direct summary of the posted observations. General statistical point: a proportion formed from a small group can vary substantially when the observed status of only a few people changes. Such counts are therefore best interpreted alongside the denominator and the study design, rather than as stable estimates of a broader population rate. No confidence intervals for these counts are reported in the registry record.
Why severity and seriousness are separate
The endpoint names severe adverse events and serious adverse events as distinct categories. The registry defines severe as Grade 3 or 4, while seriousness is determined by medical consequences such as death, life-threatening events, specified important events, or hospitalization. These classifications answer different questions. Severity describes the intensity grade; seriousness describes the event’s regulatory or clinical consequences under the registry definition. An event can be classified using one framework without the two categories being interchangeable. The record says adverse events were graded using CTCAE Version 3.0.
What the dose cohorts can show
The cohort summaries permit a descriptive view of counts across the listed dose levels. They do not constitute a randomized dose comparison. In a non-randomized dose-escalation study, dose assignment may be related to study progression and eligibility, among other possible design features; the registry record does not state the assignment rules, so those details cannot be asserted. General statistical point: an unadjusted difference between groups can reflect group composition or design as well as treatment exposure. A formal comparison would require an analysis plan and methods that account for the design, neither of which is reported in the registry record.
The groups also have different denominators: the posted safety groups list 6 participants at risk in each of three cohorts and 21 in the 10 mg/kg cohort. Unequal group sizes affect how directly raw counts can be compared. A larger count in a larger cohort does not, by itself, indicate a greater event probability; denominators matter. Conversely, turning the counts into new percentages would be a calculation beyond the posted figures and is not needed to interpret the registry’s reported summaries.
Confidence intervals and precision
General statistical point: a confidence interval describes uncertainty around an estimate under the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, while neither interval alone resolves bias or confounding. The registry record does not report confidence intervals for the adverse-event counts or comparative effects. Accordingly, the page can discuss the observed counts but cannot state how precisely they estimate event rates beyond the limitations implied by the cohort sizes and design.
Multiplicity and multiple outcomes
The record names a broad primary safety outcome with multiple event categories and lists numerous secondary outcomes, including response, progression, prostate-specific antigen, electrocardiogram, and blood-pressure measures. When many outcomes are examined, there can be multiple opportunities for apparently notable findings. General statistical point: multiplicity procedures can be used to control error rates across a family of tests, but the choice depends on the analysis objectives and prespecified plan. The registry record does not report such a plan, any adjustment for multiple testing, or inferential analyses. It is therefore not possible to determine whether or how multiplicity was addressed.
Planning illustrations are not trial results
The separate sample-size material on the page is a planning illustration computed from an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It is not the trial’s own design calculation and does not represent observed power. The assumptions describe a hypothetical planning exercise, not the actual non-randomized dose-escalation structure. Sample-size planning values should not be used to suggest that the trial had a particular probability of finding an effect, or that an unreported result is statistically conclusive. The registry record does not report the trial’s sample-size justification.
What is absent from the analysis record
The record reports zero analyses in the information. That means no inferential analysis is available to explain the event counts through hypothesis tests, adjusted models, or confidence intervals. It also does not report methods for missing data, censoring, handling multiple events, or subgroup analyses. General statistical point: the method used to handle incomplete follow-up or unavailable outcomes can influence estimates, so those procedures matter when interpreting results. Because the relevant methods and results are not reported in the registry record, no particular approach should be presumed.
The main statistical reading is consequently descriptive. Keep each count tied to its cohort denominator, distinguish seriousness from severity, do not treat dose cohorts as randomized comparators, and separate posted observations from general planning concepts. This approach respects what the registry reports without turning absent analyses into implied findings.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome covering several categories and a broad set of secondary outcomes. The secondary list includes best overall response, disease control, response timing and duration, progression measures, prostate-specific antigen outcomes, electrocardiogram changes, and blood pressure. The record also reports 20 outcome measures. This is a substantial range of possible summaries, but the statistical analysis plan and any hierarchy among outcomes are not reported in the registry record.
General statistical point: when many outcomes or comparisons are examined, the chance of finding an apparently notable result by chance can increase. Prespecified outcome priorities and multiplicity procedures can help readers understand how results were selected and interpreted. The registry record does not report whether any multiplicity adjustment was planned or used. It also reports zero analyses in the information, so no testing strategy can be reviewed.
The safety population is defined as participants who received at least one dose or any partial dose. The record does not report the number screened, reasons for exclusion, missing outcome data, or methods for handling participants with incomplete follow-up. The stated safety observation window extends from Day 1 to 70 days post last dose, with 28 days past study discontinuation, but the registry information does not explain how that window was applied to participants with different follow-up.
Results for several named safety categories and for the listed efficacy and pharmacokinetic aims are not reported in the registry record. Missing results should not be treated as negative results or as evidence that no events occurred. The death counts are also not reported in the registry record. These omissions limit a complete assessment of the planned outcome set and make it impossible to assess selective availability of results from this information alone.
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 |
|---|---|---|---|
| 0.3 mg/kg Nivolumab | 3 | 6 | 50.0% |
| 1 mg/kg Nivolumab | 5 | 6 | 83.3% |
| 3 mg/kg Nivolumab | 4 | 6 | 66.7% |
| 10 mg/kg Nivolumab | 11 | 21 | 52.4% |
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 |
|---|---|
| 0.3 mg/kg Nivolumab | 6 of 6 |
| 1 mg/kg Nivolumab | 6 of 6 |
| 3 mg/kg Nivolumab | 6 of 6 |
| 10 mg/kg Nivolumab | 21 of 21 |
Most frequent serious adverse event terms
| Event term | Organ system | 0.3 mg/kg Nivolumab | 1 mg/kg Nivolumab | 3 mg/kg Nivolumab | 10 mg/kg Nivolumab |
|---|---|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 6 | 4 of 6 | 1 of 6 | 4 of 21 |
| Anaemia | Blood and lymphatic system disorders | 0 of 6 | 1 of 6 | 2 of 6 | 0 of 21 |
| Abdominal pain | Gastrointestinal disorders | 0 of 6 | 0 of 6 | 0 of 6 | 3 of 21 |
| Pneumonia | Infections and infestations | 0 of 6 | 1 of 6 | 0 of 6 | 1 of 21 |
| Dehydration | Metabolism and nutrition disorders | 1 of 6 | 1 of 6 | 0 of 6 | 0 of 21 |
| Spinal cord compression | Nervous system disorders | 1 of 6 | 0 of 6 | 0 of 6 | 1 of 21 |
| Hyperglycaemia | Metabolism and nutrition disorders | 0 of 6 | 1 of 6 | 0 of 6 | 1 of 21 |
| Anorexia | Metabolism and nutrition disorders | 0 of 6 | 1 of 6 | 0 of 6 | 0 of 21 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 6 | 0 of 6 | 1 of 6 | 0 of 21 |
| Confusional state | Psychiatric disorders | 0 of 6 | 0 of 6 | 0 of 6 | 1 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 0.3 mg/kg Nivolumab | 1 mg/kg Nivolumab | 3 mg/kg Nivolumab | 10 mg/kg Nivolumab |
|---|---|---|---|---|---|
| Fatigue | General disorders | 2 of 6 | 5 of 6 | 4 of 6 | 12 of 21 |
| Anaemia | Blood and lymphatic system disorders | 1 of 6 | 4 of 6 | 3 of 6 | 12 of 21 |
| Blood alkaline phosphatase increased | Investigations | 2 of 6 | 2 of 6 | 3 of 6 | 13 of 21 |
| Weight decreased | Investigations | 5 of 6 | 2 of 6 | 3 of 6 | 9 of 21 |
| CD4 lymphocytes decreased | Investigations | 1 of 6 | 2 of 6 | 1 of 6 | 14 of 21 |
| Nausea | Gastrointestinal disorders | 0 of 6 | 3 of 6 | 4 of 6 | 11 of 21 |
| C-reactive protein increased | Investigations | 1 of 6 | 4 of 6 | 4 of 6 | 8 of 21 |
| Lymphopenia | Blood and lymphatic system disorders | 4 of 6 | 1 of 6 | 3 of 6 | 9 of 21 |
| Hypocalcaemia | Metabolism and nutrition disorders | 1 of 6 | 4 of 6 | 3 of 6 | 8 of 21 |
| Proteinuria | Renal and urinary disorders | 2 of 6 | 3 of 6 | 2 of 6 | 8 of 21 |
Serious events with the highest arm-level rate: malignant neoplasm progression (66.7%), anaemia (33.3%), anorexia (16.7%), back pain (16.7%), abdominal pain upper (16.7%).
The serious adverse-event figures are participant counts within the safety population and should be read together with their denominators. The registry lists 3 of 6 participants in the 0.3 mg/kg cohort, 5 of 6 in the 1 mg/kg cohort, 4 of 6 in the 3 mg/kg cohort, and 11 of 21 in the 10 mg/kg cohort. The figures describe what was recorded in these groups; they do not show that treatment caused the events.
The registry also lists other adverse events in 6 of 6, 6 of 6, 6 of 6, and 21 of 21 participants across those same dose levels. The term other adverse events should not be interpreted as meaning mild or unimportant events. The registry’s primary outcome distinguishes categories including severe, serious, drug-related, and immune-related events, which are defined differently.
Malignant neoplasm progression is listed among the top serious-event terms at 66.7%. Anaemia is listed at 33.3%, and anorexia, back pain, abdominal pain upper, and renal failure are each listed at 16.7%. These terms may describe events in overlapping participants; the record does not establish that they are mutually exclusive. The registry does not report death counts here, so they cannot be interpreted as zero. Nor do these summaries provide event timing, duration, or participant-level attribution.
Because allocation was non-randomized and there was no control group, the cohort figures are not a like-for-like comparison. They are descriptive safety information from this study, not a comparative estimate of risk.
12. What the Result Does, and Does Not, Mean
This record describes a completed phase 1 dose-escalation study of MDX-1106 in participants with selected relapsed or refractory malignancies. Its posted safety data show that serious adverse events were recorded in each of the four dose cohorts, and that other adverse events were recorded for all participants listed as at risk in each cohort. The registry also identifies several serious-event terms, including malignant neoplasm progression and anaemia.
These observations are relevant to describing the safety experience recorded during the study’s defined observation period. They do not establish that MDX-1106 caused any particular event. The registry’s adverse-event definitions allow events that may not have a causal relationship with treatment, and the group summaries do not give participant-level attribution for each event. Seriousness and severity are distinct classifications, and the posted counts should not be read as if they were the same measure.
The study does not provide a randomized control group. Consequently, its dose cohorts cannot establish what would have happened to comparable participants without the study drug or under another treatment. The cohort counts also do not demonstrate a dose-response relationship. Any apparent pattern across the listed doses could not be interpreted as a causal dose effect from these figures alone.
The registry describes efficacy and pharmacokinetic aims and lists related secondary outcomes, but numerical results for them are not reported in the registry record. The record also does not report death counts, confidence intervals, or inferential analyses. Therefore, the posted safety figures cannot answer whether the study drug affected tumor response, progression, survival, or other clinical outcomes.
In short, the data support a descriptive account of recorded events in this early-phase study. They do not support a comparative effectiveness conclusion, a causal claim, or a complete account of all prespecified outcomes. The absence of a reported value is not evidence that the outcome did not occur.
13. Why This Trial Matters Statistically
This trial illustrates why early-phase dose-escalation studies and randomized comparative trials answer different statistical questions. Here, the design is non-randomized and single-group, with participants assigned to listed dose cohorts. Its primary emphasis is safety characterization, not estimation of a treatment contrast against a control group. Reading the cohort counts as if they were randomized-arm results would give them a meaning the design does not support.
It also shows why denominator and outcome definition matter. The same study reports serious adverse events and other adverse events separately, while defining severe events by grade and serious events by consequences. These categories are not interchangeable. Keeping the definitions distinct prevents a simple count from being given a misleading clinical or statistical interpretation.
The record’s range of secondary outcomes is another important statistical feature. Response, progression, prostate-specific antigen, electrocardiogram, and blood-pressure outcomes address different questions and may require different methods and analysis populations. Without reported analysis methods and outcome results, readers cannot determine how those measures were summarized, whether comparisons were planned, or how multiplicity was handled.
Finally, this record highlights the difference between observed data and planning calculations. A sample-size illustration based on an observed effect is not the trial’s original sample-size justification and is not observed power. Such planning material can help explain hypothetical future study requirements, but it cannot substitute for the missing inferential results from this trial.
The statistical value of the record is therefore in its structured description of design, safety population, observation window, and event counts, alongside a clear account of what remains unreported. That distinction is essential when interpreting a small early-phase study without a control group.
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 study enrolled 39 participants across several malignancy types, and the listed dose cohorts are non-randomized. The resulting event counts are descriptive and do not provide a controlled estimate of treatment effect. The record does not report a disease-specific analysis, so the combined safety summaries should not be assumed to characterize each malignancy group separately.
The cohort sizes listed for the safety figures are uneven, with 6 participants at risk in each of three dose groups and 21 in the 10 mg/kg group. Counts across these cohorts are not direct evidence of dose-related differences. The registry record does not report a statistical comparison, adjustment for cohort characteristics, or uncertainty intervals.
The primary outcome title covers several safety categories, but numerical results are not reported for drug-related events, deaths, discontinuations due to adverse events, dose-limiting toxicity, or immune-related adverse events. The registry record does not report death counts, which must not be interpreted as zero. Numerical results for the named efficacy and pharmacokinetic outcomes are also not reported in the record.
Further limitations include the absence of reported analysis methods, missing-data procedures, multiplicity handling, and sample-size justification. The record describes a safety observation window but does not explain the completeness of follow-up or how incomplete observations were handled. The serious-event terms are summarized without participant-level detail, timing, or attribution, and the listed terms may overlap.
These limitations do not erase the value of the posted counts, but they restrict the conclusions that can be drawn from them. The record supports a description of recorded events in this study, not a causal or comparative conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies — NCT00441337.
- Registry record last updated 2015-02-20; status last verified 2015-02.
- Results first posted 2015-02-20.
- 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
NCT00441337 is a completed phase 1, open-label, non-randomized, single-group dose-escalation study of MDX-1106, identified in the arm descriptions as nivolumab. The registry lists 39 participants enrolled, four intravenous dose levels, and several advanced or refractory malignancy types.
The primary outcome concerns participant counts for specified adverse-event categories in the safety population, defined as those who received at least one dose or any partial dose. The posted serious-event counts are 3 of 6, 5 of 6, 4 of 6, and 11 of 21 across the listed dose groups. The record also lists other adverse events for all participants at risk in each cohort.
These are descriptive results from non-randomized cohorts, not a controlled comparison. Numerical results for several named safety, efficacy, and pharmacokinetic outcomes, death counts, and inferential analyses are not reported in the registry record. The posted information therefore supports a limited account of safety observations, not a causal or comparative treatment conclusion.