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 Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread (NCT03459222), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Grade 3/Grade 4 Laboratory Test Results.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03459222 |
| Phase | Phase 1, Phase 2 |
| Condition | Advanced Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 229 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with advanced malignant tumors, described in the registry as advanced cancer. The study included immunotherapy-naive and pretreated populations across selected tumor types. Its primary endpoint population was all treated participants, with only participants available at the relevant timepoint included in the analysis.
Intervention
The study evaluated relatlimab in combination with nivolumab and BMS-986205, or relatlimab in combination with nivolumab and ipilimumab. The registry describes these as investigational combinations and states that the study’s purpose was to assess safety and preliminary activity.
Comparator
The listed regimens were assigned to non-randomized parallel arms. The registry does not describe a randomized control group, and it cautions that the arms are not a like-for-like control comparison. Differences between their outcomes therefore cannot be interpreted as if they came from a randomized head-to-head trial.
Primary question
The primary endpoint counts participants with Grade 3 or Grade 4 laboratory test results during treatment and the specified follow-up window. The registry record does not report the endpoint’s observed counts or any comparison of the combinations on this measure. Progression-free survival and progression-free survival rates at 6 and 12 months are listed as secondary outcomes, but their results are not reported in the registry record.
3. Trial Design
This is a Phase 1/2, non-randomized, open-label, parallel study of immunotherapy combinations in participants with advanced malignant tumors. The registry lists an enrollment of 229 and marks the study as completed. Its recorded start date is 2018-05-30, and the primary completion date is 2025-02-19.
Arm A is described as relatlimab plus nivolumab plus BMS-986205. Arm B is described as relatlimab plus nivolumab plus ipilimumab. The registry also lists several dose-escalation and tumor-specific cohorts, including cohorts identified by cancer type and immunotherapy history. These cohort labels show that the study included varied clinical groups; they do not establish that those groups were balanced or directly comparable.
Because allocation was non-randomized and masking was absent, treatment assignment was not concealed through random allocation, and participants and study personnel were not masked. The registry record does not report the assignment procedure, eligibility details for each cohort, or a protocol rationale for the cohort structure. It also does not report a sample-size justification or describe an inferential plan for comparing the arms.
The study purpose was to assess safety and preliminary activity. Progression-free survival and progression-free survival rates at 6 and 12 months are listed among the secondary outcomes. The primary endpoint concerns participants with Grade 3 or Grade 4 laboratory test results. Although the registry marks the study completed, numerical results for that primary endpoint and the listed secondary outcomes 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.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | 1A-esc-480/160/25 | 1A-esc-480/160/50 | 1A-esc-480/160/100 | 1B-esc-160/480/1 | 2A-SCCHN IO Naive-160/480/100 | 2A-MEL 1L-160/480/100 |
|---|---|---|---|---|---|---|
| STARTED | 3 | 3 | 7 | 6 | 45 | 54 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 3 |
| NOT COMPLETED | 3 | 3 | 7 | 6 | 45 | 51 |
Reasons for not completing this period:
| Reason | 1A-esc-480/160/25 | 1A-esc-480/160/50 | 1A-esc-480/160/100 | 1B-esc-160/480/1 | 2A-SCCHN IO Naive-160/480/100 | 2A-MEL 1L-160/480/100 |
|---|---|---|---|---|---|---|
| Participant request to discontinue study treatment | 0 | 0 | 0 | 0 | 0 | 2 |
| Participant withdrew consent | 0 | 0 | 0 | 0 | 0 | 0 |
| Death | 0 | 0 | 0 | 0 | 2 | 1 |
| Adverse event unrelated to study drug | 0 | 0 | 0 | 0 | 4 | 0 |
| Disease recurrence | 0 | 0 | 0 | 0 | 1 | 0 |
| Other Reasons | 0 | 1 | 2 | 0 | 0 | 4 |
| Disease progression | 2 | 2 | 3 | 6 | 30 | 25 |
| Study drug toxicity | 0 | 0 | 2 | 0 | 8 | 16 |
| Maximum clinical benefit | 1 | 0 | 0 | 0 | 0 | 3 |
Analysis population for the primary outcome, as defined in the registry: All treated participants. Only participants available at timepoint were included in the analysis.
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 9 groups are shown.
| Characteristic | Unit | 1A-esc-480/160/25 | 1A-esc-480/160/50 | 1A-esc-480/160/100 | 1B-esc-160/480/1 | 2A-SCCHN IO Naive-160/480/100 | 2A-MEL 1L-160/480/100 |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 7 | 6 | 45 | 54 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 3 | 3 | 4 | 30 | 38 |
| Age, Categorical: >=65 years | Participants | 1 | 0 | 4 | 2 | 15 | 16 |
| Sex: Female, Male: Female | Participants | 1 | 0 | 4 | 3 | 11 | 23 |
| Sex: Female, Male: Male | Participants | 2 | 3 | 3 | 3 | 34 | 31 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 7 | 6 | 27 | 25 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 18 | 29 |
| Race/Ethnicity, Customized: White | Participants | 2 | 2 | 7 | 5 | 36 | 41 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 | 0 | 0 | 1 | 1 | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 1 | 0 | 0 | 0 | 1 | 0 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 1 | 0 | 0 | 4 | 3 |
| Race/Ethnicity, Customized: Not reported | Participants | 0 | 0 | 0 | 0 | 3 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Grade 3/Grade 4 Laboratory Test Results, measured over From first dose (Day 1) and within 30 days of last dose of study therapy (up to approximately 69 months).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with Grade 3 or Grade 4 laboratory test results. Laboratory results are graded using the Common Terminology Criteria for Adverse Events, Version 3.0. In that grading system, Grade 3 is defined as severe or medically significant but not immediately life-threatening; Grade 4 is defined as life-threatening or disabling.
The endpoint covers the period from first dose on Day 1 through 30 days after the last dose of study therapy, with the registry describing the duration as up to approximately 69 months. The analysis population is all treated participants, but only participants available at a given timepoint were included. As a general statistical consideration, a participant count describes how many people met the event definition; it does not by itself show how laboratory monitoring, time under observation, or missing measurements differed among cohorts.
The endpoint can characterize the occurrence of severe laboratory abnormalities during the specified treatment and follow-up period. It is a safety measure, not a direct measure of tumor response or progression-free survival. The registry record does not report the observed endpoint counts, laboratory-specific results, or any effect estimate comparing regimens, so the endpoint’s findings cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The available registry information describes the study design and defines the primary safety endpoint, but it does not give the primary endpoint’s observed results. There are no posted counts of participants with Grade 3 or Grade 4 laboratory results, nor estimates of uncertainty or a reported comparison between regimens. The endpoint definition alone cannot indicate how often such results occurred or whether their frequency differed between cohorts.
The same distinction applies to the secondary outcomes. Progression-free survival and progression-free survival rates at 6 and 12 months are listed, but their numerical results are not reported in the registry record. The registry lists eight outcome measures and zero analysis entries. This describes the record’s analysis listings; it does not establish whether analyses were conducted outside the registry.
The study’s non-randomized allocation is central to interpretation. As a general statistical principle, random allocation can help balance measured and unmeasured prognostic factors across treatment groups. Without it, the populations receiving the regimens may differ in tumor type, treatment history, disease characteristics, or other factors. The registry’s cohort labels themselves indicate variation in cancer type and immunotherapy history. An outcome difference across such cohorts, if available, would not by itself identify a treatment effect.
The posted serious adverse event listings give counts by cohort and include selected serious-event terms with percentages. These data are descriptive. The cohort labels and denominators differ, and the registry cautions that the arms are not a like-for-like control comparison. The listed counts do not establish that an event was caused by a study drug, and deaths listed by cohort should not be treated as treatment-attributable without information on cause and attribution. That information is not reported in the registry record.
Interpretation is also constrained by the primary endpoint’s available-at-timepoint rule. As a general statistical consideration, if laboratory observations are missing or follow-up differs across participants, the observed count may not represent all treated participants in the same way. The extent and handling of missing laboratory data are not reported in the registry record. Consequently, the registry supports a description of study structure and selected safety listings, but not a quantitative judgment about comparative safety or activity.
9. Statistical Methods Explained
Several statistical ideas help distinguish what the registry record defines from what its results establish. The record identifies a primary endpoint and lists secondary outcomes, but numerical primary or secondary outcome results are not reported in the registry record. The following explanations are general statistical context, not a description of analyses confirmed to have been conducted in this study.
What does a participant count measure?
A count of participants with an event records how many people met a defined criterion during a specified observation period. It is not the same as a continuous laboratory measurement, and it does not show the severity distribution beyond the Grade 3/Grade 4 definition. A count also does not automatically account for how long participants were observed or how often measurements were collected. When groups have different follow-up or different availability of measurements, comparing raw counts can be difficult to interpret.
For this study, the endpoint definition uses CTCAE Version 3.0 grades and a window from first dose through 30 days after the last dose, up to approximately 69 months. The analysis includes all treated participants who were available at the timepoint. The endpoint’s actual counts and any rates or estimates based on those counts are not reported in the registry record.
Why does non-randomized allocation matter?
In a randomized study, assignment by chance is intended to reduce systematic differences between treatment groups. In a non-randomized study, treatment assignment may be associated with patient or disease characteristics. Those characteristics may also be related to outcomes, creating confounding. Statistical adjustment can sometimes address measured differences, but it cannot guarantee removal of unmeasured differences.
Here, the arms are non-randomized and the registry explicitly says they are not a like-for-like control comparison. The listed cohorts differ in tumor type and treatment-history labels. Any observed contrast between regimens would therefore need to be interpreted as an association within these study groups unless a suitable analysis and its assumptions were documented. The registry record does not report an adjusted comparative analysis.
What would uncertainty estimates add?
A confidence interval is a general statistical tool that describes uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision under those assumptions, while a wide interval indicates less precision. A p-value, when used, addresses compatibility between data and a specified statistical model under a null hypothesis; it does not measure the size or clinical importance of an effect. Neither an interval nor a p-value can correct a poorly matched comparison or unaddressed bias.
No confidence intervals, p-values, or other primary-endpoint effect estimates are reported in the registry record. The absence of these reported quantities means readers cannot judge the precision of a primary-endpoint contrast from the registry record.
How should planning calculations be read?
Sample-size calculations are planning illustrations, not evidence about what the trial observed and not “observed power.” The stated assumptions for the illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the stated calculation convention is a total number of events; for other outcomes, it is participants per arm. These assumptions describe the planning illustrations and should not be mistaken for the trial’s own design rationale or statistical plan. That rationale and plan are not reported in the registry record.
In general, planning calculations depend on their assumptions about the target effect, variability or event frequency, allocation, and analysis. When an observed effect is used as a reference, the resulting illustration is conditional on that estimate and does not establish that a future study would reproduce it. The registry record’s stated assumptions do not supply evidence about the achieved precision of this trial’s endpoints.
Why can over-dispersion matter?
As a general concept, over-dispersion occurs when outcome variability exceeds what a statistical model assumes. A model that underestimates variability can produce uncertainty estimates that are too small. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report the model used for the primary endpoint, so it is not possible to assess whether this issue was evaluated in the study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary laboratory safety outcome and secondary outcomes for progression-free survival and progression-free survival rates at 6 and 12 months. When a study assesses several outcomes, the chance of at least one apparently notable result can increase if each is tested separately. General approaches to multiplicity include prespecifying a hierarchy of outcomes, adjusting significance thresholds, or treating analyses as exploratory. The registry record does not report whether multiplicity was addressed, how outcomes were prioritized beyond their listed status, or what statistical tests were planned.
The registry lists eight outcome measures and zero analysis entries. This is a description of the registry record, not proof that no analysis took place. Numerical results, analysis populations beyond the primary endpoint description, and methods for handling repeated measurements or competing events are not reported in the registry record.
For the primary endpoint, the stated population is all treated participants, with only participants available at the timepoint included. This makes availability relevant to interpretation. In general, missing outcome measurements can bias a count if availability is related to health status, treatment exposure, or the likelihood of an event. The amount and pattern of missing laboratory data, the reasons for missingness, and any imputation or sensitivity analysis are not reported in the registry record.
The registry does not report a sample-size justification, interim analyses, or a detailed statistical analysis plan. Without those details and numerical outcome results, readers cannot determine how the study’s planned inferential procedures handled multiplicity, missing data, or differences among cohorts.
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 |
|---|---|---|---|
| 1A-esc-480/160/25 | 1 | 3 | 33.3% |
| 1A-esc-480/160/50 | 1 | 3 | 33.3% |
| 1A-esc-480/160/100 | 6 | 7 | 85.7% |
| 1B-esc-160/480/1 | 4 | 6 | 66.7% |
| 2A-SCCHN IO Naive-160/480/100 | 29 | 45 | 64.4% |
| 2A-MEL 1L-160/480/100 | 21 | 54 | 38.9% |
| 2B-NSCLC 1L-160/480/1 | 38 | 65 | 58.5% |
| 2B-MEL 1L-160/480/1 | 27 | 46 | 58.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 1A-esc-480/160/25 | 2 of 3 |
| 1A-esc-480/160/50 | 2 of 3 |
| 1A-esc-480/160/100 | 5 of 7 |
| 1B-esc-160/480/1 | 3 of 6 |
| 2A-SCCHN IO Naive-160/480/100 | 35 of 45 |
| 2A-MEL 1L-160/480/100 | 21 of 54 |
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 |
|---|---|
| 1A-esc-480/160/25 | 3 of 3 |
| 1A-esc-480/160/50 | 3 of 3 |
| 1A-esc-480/160/100 | 7 of 7 |
| 1B-esc-160/480/1 | 6 of 6 |
| 2A-SCCHN IO Naive-160/480/100 | 36 of 45 |
| 2A-MEL 1L-160/480/100 | 52 of 54 |
Most frequent serious adverse event terms
| Event term | Organ system | 1A-esc-480/160/25 | 1A-esc-480/160/50 | 1A-esc-480/160/100 | 1B-esc-160/480/1 | 2A-SCCHN IO Naive-160/480/100 | 2A-MEL 1L-160/480/100 |
|---|---|---|---|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 3 | 0 of 3 | 2 of 7 | 0 of 6 | 3 of 45 | 2 of 54 |
| Alanine aminotransferase increased | Investigations | 0 of 3 | 0 of 3 | 1 of 7 | 0 of 6 | 2 of 45 | 2 of 54 |
| Aspartate aminotransferase increased | Investigations | 0 of 3 | 0 of 3 | 1 of 7 | 0 of 6 | 2 of 45 | 2 of 54 |
| Pneumonia | Infections and infestations | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 4 of 45 | 0 of 54 |
| Hepatic cytolysis | Hepatobiliary disorders | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 2 of 45 | 1 of 54 |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 3 of 45 | 0 of 54 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 1 of 45 | 2 of 54 |
| Colitis | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 1 of 45 | 1 of 54 |
| Nausea | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 1 of 45 | 1 of 54 |
| Asthenia | General disorders | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 1 of 45 | 1 of 54 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 1A-esc-480/160/25 | 1A-esc-480/160/50 | 1A-esc-480/160/100 | 1B-esc-160/480/1 | 2A-SCCHN IO Naive-160/480/100 | 2A-MEL 1L-160/480/100 |
|---|---|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | 1 of 3 | 0 of 3 | 1 of 7 | 0 of 6 | 6 of 45 | 28 of 54 |
| Aspartate aminotransferase increased | Investigations | 1 of 3 | 0 of 3 | 1 of 7 | 0 of 6 | 6 of 45 | 26 of 54 |
| Asthenia | General disorders | 0 of 3 | 0 of 3 | 0 of 7 | 0 of 6 | 17 of 45 | 11 of 54 |
| Nausea | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 2 of 7 | 3 of 6 | 2 of 45 | 17 of 54 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 3 | 0 of 3 | 2 of 7 | 2 of 6 | 7 of 45 | 12 of 54 |
| Anaemia | Blood and lymphatic system disorders | 0 of 3 | 0 of 3 | 1 of 7 | 0 of 6 | 12 of 45 | 10 of 54 |
| Constipation | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 1 of 7 | 2 of 6 | 6 of 45 | 11 of 54 |
| Fatigue | General disorders | 0 of 3 | 1 of 3 | 2 of 7 | 3 of 6 | 6 of 45 | 8 of 54 |
| Diarrhoea | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 1 of 7 | 2 of 6 | 5 of 45 | 8 of 54 |
| Headache | Nervous system disorders | 1 of 3 | 1 of 3 | 1 of 7 | 2 of 6 | 3 of 45 | 8 of 54 |
Serious events with the highest arm-level rate: acute myocardial infarction (33.3%), fall (33.3%), pelvic fracture (33.3%), malignant neoplasm progression (28.6%), adrenal insufficiency (16.7%).
The registry’s safety listings separate serious events, other events, and deaths by cohort. For each cohort, the listing gives the number at risk and the number affected. These are counts, not comparative rates, and should be read within each cohort rather than treated as a direct ranking of regimens.
For serious events, the at-risk and affected counts are 3 and 1 for 1A-esc-480/160/25; 3 and 1 for 1A-esc-480/160/50; 7 and 6 for 1A-esc-480/160/100; 6 and 4 for 1B-esc-160/480/1; 45 and 29 for 2A-SCCHN IO Naive-160/480/100; 54 and 21 for 2A-MEL 1L-160/480/100; 65 and 38 for 2B-NSCLC 1L-160/480/1; and 46 and 27 for 2B-MEL 1L-160/480/1. The corresponding other-event counts are 3 and 3, 3 and 3, 7 and 7, 6 and 6, 45 and 36, 54 and 52, 65 and 63, and 46 and 43.
Deaths are listed by cohort, but the registry record does not report their causes or attribution to study treatment. The selected serious-event terms include acute myocardial infarction, fall, pelvic fracture, malignant neoplasm progression, adrenal insufficiency, and hypopituitarism, with the listed percentages ranging from 16.7% to 33.3%. Denominators for those percentages are not reported in the registry record. These descriptive listings cannot establish comparative risk or causation.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed Phase 1/2 study evaluated relatlimab-based combinations in advanced malignant tumors and specified a laboratory safety endpoint based on Grade 3 or Grade 4 results. It also gives cohort-level listings for serious events, other events, and deaths. These details describe what was studied and what safety information is listed.
The record does not report the numerical results for the primary laboratory endpoint or the listed progression-free survival outcomes. It therefore does not establish how often participants experienced the primary endpoint, how precisely any outcome was estimated, or whether one regimen had better or worse outcomes than another. The absence of reported outcome analyses is not evidence that outcomes were absent or that no analyses were conducted.
Even if comparative outcomes were available, the non-randomized allocation and the registry’s warning against treating the arms as like-for-like controls would limit causal conclusions. Differences between cohorts could reflect their cancer types, treatment histories, or other characteristics rather than the assigned regimen. General statistical adjustment may reduce some measured differences, but the registry record does not report an adjusted comparison or the information needed to assess such adjustment.
The safety listings likewise do not prove that the listed events were caused by treatment. The listed deaths have no reported causal attribution, and the serious-event term percentages lack reported denominators. Counts across cohorts with different sizes and case mix should not be compared as though they were randomized group rates.
Accordingly, the registry record supports a limited descriptive reading of design, endpoint definitions, and selected safety counts. It does not support a definitive conclusion about comparative safety, treatment efficacy, or the balance of benefit and harm. Those conclusions would require outcome results and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why trial design and reporting details matter alongside endpoint definitions. A registry may identify the intended safety question and list clinically relevant secondary outcomes, yet without numerical results readers cannot assess the observed magnitude or precision of the findings. For this record, the laboratory endpoint is clearly defined by CTCAE grades and an observation window, but its event counts and estimates are not reported.
The non-randomized structure also illustrates a core challenge in clinical biostatistics: comparing groups that may differ before treatment. The registry describes varied tumor-specific and treatment-history cohorts and explicitly cautions that the arms are not a like-for-like control comparison. This makes causal interpretation especially dependent on a transparent account of assignment, baseline characteristics, analysis methods, and assumptions. Those details are not reported in the registry record.
Safety counts also demonstrate why denominators, follow-up, and event attribution matter. A count alone does not describe risk over time or establish causation. Percentages without their denominators are difficult to contextualize, and deaths without reported attribution cannot be assigned to a regimen based on the listing alone.
Finally, the record lists progression-free survival outcomes and planning assumptions but does not report outcome analyses or a detailed statistical plan. Keeping planning illustrations distinct from observed results, and distinguishing a descriptive signal from a causal treatment effect, are essential practices when interpreting early-phase, non-randomized research.
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 for interpreting outcomes is that numerical primary and secondary endpoint results are not reported in the registry record. The primary endpoint’s observed counts, effect estimates, and uncertainty measures are unavailable, as are the listed progression-free survival results. The record therefore does not permit quantitative evaluation of those outcomes.
The non-randomized allocation limits direct comparisons between the regimens. The study includes tumor-specific and treatment-history cohorts, and the registry cautions that the arms are not like-for-like controls. Cohort differences may complicate interpretation even if outcome contrasts were available. The registry record does not report an adjusted comparison, baseline balance, or a method for addressing confounding.
The primary endpoint includes only participants available at the timepoint, but the extent and reasons for missing laboratory results are not reported. The registry record also does not report how missing data were handled, whether sensitivity analyses were conducted, or whether observation time differed across participants.
The safety listings are descriptive. The record does not report cause or treatment attribution for the listed deaths, and it does not give denominators for the selected serious-event term percentages. The listed counts should not be taken as causal estimates or used to infer comparative risk across cohorts.
Additional limitations include the absence of a reported sample-size justification, detailed statistical analysis plan, multiplicity approach, and interim-analysis information. The registry’s zero analysis entries do not establish that analyses were not performed, but the record does not provide analyses that can be evaluated. Together, these omissions constrain conclusions about both precision and comparative effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread — NCT03459222.
- Registry record last updated 2026-04-06; status last verified 2026-03.
- Results first posted 2026-04-06.
- 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 identifies NCT03459222 as a completed Phase 1/2, non-randomized, open-label, parallel study with an enrollment of 229. It evaluated relatlimab with nivolumab and BMS-986205, or relatlimab with nivolumab and ipilimumab, in participants with advanced malignant tumors.
The primary endpoint counts participants with Grade 3 or Grade 4 laboratory test results from first dose through 30 days after the last dose, up to approximately 69 months. Progression-free survival and progression-free survival rates at 6 and 12 months are listed as secondary outcomes. The registry record does not report numerical results for these outcomes or a detailed analysis plan. Cohort-level listings describe serious events, other events, and deaths, but they do not establish treatment causation or provide a like-for-like comparison of the regimens.