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 to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma, Transformed Follicular Lymphoma, Other Non-Hodgkin's Lymphomas, Solid Tumors and Multiple Myeloma (NCT02082977), a non-randomized phase 1 study. The primary outcome is Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02082977 |
| Phase | Phase 1 |
| Condition | Cancer, Neoplasms |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 41 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Part 1 enrolled adults with relapsed or refractory diffuse large B cell lymphoma, transformed follicular lymphoma, other non-Hodgkin's lymphomas, solid tumors, or multiple myeloma. The study planned a Part 2 expansion for specified lymphoma groups and multiple myeloma. The primary safety analysis population included participants who received at least one dose of study treatment.
Intervention
Participants received GSK2816126 by intravenous infusion, twice weekly. Part 1 used sequential dose groups from 50 mg through 3000 mg, with each described regimen given for 28 days on a 3-weeks-on/1-week-off schedule. Part 2 was planned to use the recommended Phase 2 dose.
Comparator
There was no randomized control group. The study was open-label, non-randomized, and sequential, so the different dose groups do not constitute a like-for-like comparison against an untreated or active-control group. Participants and study staff were not masked.
Primary question
Part 1's primary outcome counted participants with serious and non-serious adverse events during a timeframe of up to 3.2 years. The broader study aimed to investigate safety, pharmacokinetics, pharmacodynamics, and clinical activity, and to determine a recommended Phase 2 dose. The registry record does not report an outcome estimate for clinical activity or the recommended dose.
3. Trial Design
This was a Phase I, open-label, multicenter, two-part study of GSK2816126. Part 1 used a sequential dose-escalation design in adults with relapsed or refractory diffuse large B cell lymphoma, transformed follicular lymphoma, other non-Hodgkin's lymphomas, solid tumors, or multiple myeloma. The listed twice-weekly dose groups were 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, 1800 mg, 2400 mg, and 3000 mg. Each Part 1 regimen was described as an intravenous solution for 28 days, on a 3-weeks-on/1-week-off schedule.
The planned Part 2 expansion was intended to explore clinical activity at the recommended Phase 2 dose in specified groups, including EZH2 wild type and mutant positive germinal center B-cell-like diffuse large B cell lymphoma, transformed follicular lymphoma, and multiple myeloma. The registry record describes the planned expansion but reports zero participants at risk in its Part 2 safety group. The recommended Phase 2 dose is not reported in the registry record.
Enrollment was 41. The study started on 2014-04-24, had a primary completion date of 2017-06-20, and is listed as terminated. The reason for termination is not reported in the registry record. Random allocation and masking were not used. These features are important when reading across dose groups: the groups arose within a dose-escalation study, not through randomized assignment to comparable treatment strategies. Participant characteristics, follow-up, and the decision process for moving between doses are not reported in the registry record.
The primary outcome concerned the number of participants with serious and non-serious adverse events in Part 1. The listed secondary outcomes focus on pharmacokinetic measures such as concentrations and area under the concentration-time curve. Although clinical activity was part of the study's aims, efficacy results 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: This study was terminated prior to the completion of Part 1 due to an unfavorable benefit risk profile. Part 2 was not conducted. Approximately 42 participants screened, of which 41 were treated in Part 1 including 20 participants with lymphoma and 21 with solid tumors, of these 22 completed, 5 died and 14 participants were withdrawn.
Only the first 6 of 10 groups are shown.
Part 1 (Up to 3.2 Years)
| Stage | Part 1:GSK2816126 50 mg Twice-weekly | Part 1:GSK2816126 100 mg Twice-weekly | Part 1:GSK2816126 200 mg Twice-weekly | Part 1:GSK2816126 400 mg Twice-weekly | Part 1:GSK2816126 800 mg Twice-weekly | Part 1:GSK2816126 1200 mg Twice-weekly |
|---|---|---|---|---|---|---|
| STARTED | 2 | 1 | 1 | 1 | 3 | 4 |
| COMPLETED | 1 | 1 | 1 | 1 | 2 | 1 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 1 | 3 |
Reasons for not completing this period:
| Reason | Part 1:GSK2816126 50 mg Twice-weekly | Part 1:GSK2816126 100 mg Twice-weekly | Part 1:GSK2816126 200 mg Twice-weekly | Part 1:GSK2816126 400 mg Twice-weekly | Part 1:GSK2816126 800 mg Twice-weekly | Part 1:GSK2816126 1200 mg Twice-weekly |
|---|---|---|---|---|---|---|
| Death | 1 | 0 | 0 | 0 | 0 | 1 |
| Study closed/terminated | 0 | 0 | 0 | 0 | 0 | 0 |
| Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Physician Decision | 0 | 0 | 0 | 0 | 1 | 1 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 |
Part 2 (Up to 3.2 Years)
| Stage | Part 1:GSK2816126 50 mg Twice-weekly | Part 1:GSK2816126 100 mg Twice-weekly | Part 1:GSK2816126 200 mg Twice-weekly | Part 1:GSK2816126 400 mg Twice-weekly | Part 1:GSK2816126 800 mg Twice-weekly | Part 1:GSK2816126 1200 mg Twice-weekly |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All Subjects Population
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: Data was not collected in Part 2 of the study as no participant was enrolled in Part 2.
Only the first 6 of 11 groups are shown.
| Characteristic | Unit | Part 1:GSK2816126 50 mg Twice-weekly | Part 1:GSK2816126 100 mg Twice-weekly | Part 1:GSK2816126 200 mg Twice-weekly | Part 1:GSK2816126 400 mg Twice-weekly | Part 1:GSK2816126 800 mg Twice-weekly | Part 1:GSK2816126 1200 mg Twice-weekly |
|---|---|---|---|---|---|---|---|
| Participants analysed | 2 | 1 | 1 | 1 | 3 | 4 | |
| Age, Continuous | Years | 44.0 (SD 12.73) | 54.0 (SD NA) | 56.0 (SD NA) | 69.0 (SD NA) | 53.3 (SD 4.04) | 49.5 (SD 17.18) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 | 0 | 2 | 1 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 1 | 1 | 1 | 3 |
| Race/Ethnicity, Customized: African American/African Heritage | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Asian-Central/South Asian Heritage | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White - White/Caucasian/European Heritage | Participants | 2 | 1 | 1 | 1 | 3 | 4 |
| Race/Ethnicity, Customized: Mixed white race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Unknown | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs), measured over Up to 3.2 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome counts participants with serious adverse events (SAEs) and non-serious adverse events (non-SAEs). An adverse event is defined in the registry as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. The SAE definition includes events such as death, life-threatening events, hospitalization or prolonged hospitalization, disability or incapacity, congenital anomaly or birth defect, and specified other situations, including those associated with liver injury or impaired liver function.
This kind of safety outcome is used in early-phase studies to describe how many treated participants experienced events meeting the stated definitions. Counts can help characterize observed safety experience across dose groups, but they do not establish that treatment caused an event. The registry description says the analysis included all participants who received at least one dose of study treatment. The timeframe is up to 3.2 years.
Counts are not the same as event rates per unit of time: the outcome reports participants with events, not the number of event episodes or person-time. The registry record does not provide event onset, duration, severity grading beyond the SAE classification, relatedness assessments, or exposure-adjusted results in the primary outcome description. The posted figures should therefore be read as participant counts within the listed groups, alongside the stated population and timeframe, rather than as a causal comparison between dose levels.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety counts describe the Part 1 participants in each dose group. In the 50 mg group, 1 of 2 participants had an SAE and 2 of 2 had a non-SAE; the group lists 1 death. In the 100 mg, 200 mg, and 400 mg groups, no participant had an SAE, while 1 of 1 in each group had a non-SAE; no deaths are listed in those groups. In the 800 mg group, 1 of 3 participants had an SAE and 3 of 3 had a non-SAE, with no deaths listed. In the 1200 mg group, 2 of 4 had an SAE and 4 of 4 had a non-SAE; 1 death is listed. In the 1800 mg group, 1 of 10 had an SAE and 10 of 10 had a non-SAE; 2 deaths are listed. In the 2400 mg group, 5 of 12 had an SAE and 12 of 12 had a non-SAE, with no deaths listed. In the 3000 mg group, 3 of 7 had an SAE and 7 of 7 had a non-SAE; 1 death is listed. The Part 2 safety group lists zero participants at risk and zero affected.
These are descriptive counts, not evidence of a dose-response relationship. The study was sequential and non-randomized, and the number of participants varies across dose groups. A difference in counts between groups could reflect the different group sizes, participant mix, exposure, follow-up, or chance; the registry record does not report enough information to separate those possibilities. The registry record also does not provide a randomized control group, adjusted estimates, confidence intervals, or statistical tests comparing dose groups.
The death counts are reported by group, but cause and relationship to study treatment are not reported in the registry record. They should not be interpreted as treatment-related deaths from these counts alone. Likewise, a reported adverse event is not necessarily caused by the study drug: the registry definition explicitly includes events whether or not considered related to the medicinal product. The record does not provide detailed event-level narratives or attribution for these counts.
The registry lists respiratory tract infection at 50.0% among top serious adverse event terms, and Campylobacter infection, enterocolitis, and tumour pain at 33.3% each; pyrexia and bronchitis are listed at 25.0% each. The denominator and method used for these term percentages are not reported in the registry record. These terms complement, but do not replace, the participant counts by dose group.
The study's safety results are the available primary outcome information in the registry record. Clinical activity, pharmacokinetic outcome estimates, and the final recommended Phase 2 dose are not reported in the registry record, so the safety counts cannot answer those other study aims.
9. Statistical Methods Explained
What does a participant count represent?
The primary outcome is expressed as the number of participants with at least one event in the relevant category. A participant count is different from an event count: one participant may have experienced more than one event, but the outcome as described counts participants rather than every episode. It is also different from a rate that accounts for time at risk. In general, event rates can incorporate differing observation time, while simple participant counts do not. The primary outcome timeframe is up to 3.2 years, but group-specific observation time is not reported in the registry record.
The reported categories are serious and non-serious adverse events. These categories describe event classification, not necessarily causation. The registry defines an adverse event as a medical occurrence temporally associated with use of a medicinal product, regardless of whether it is considered related. SAEs have additional seriousness criteria, including death, life-threatening events, hospitalization or prolonged hospitalization, disability or incapacity, congenital anomaly or birth defect, and specified other situations. The record does not provide a complete account of event severity grades or treatment relatedness for each participant.
Why does the dose-escalation structure matter?
Part 1 was sequential and non-randomized. In general, randomization helps balance measured and unmeasured participant characteristics across comparison groups; without it, groups may differ in ways that influence outcomes. Sequential dose escalation also means that dose groups are not equivalent to concurrent randomized arms. The registry record does not describe the criteria used to advance doses or provide enough participant-level detail to assess comparability. Therefore, raw counts across doses are descriptive and should not be treated as a controlled estimate of the effect of changing dose.
Group sizes are small, ranging from 1 participant in some lower-dose groups to 12 in the 2400 mg group. With small groups, each participant represents a substantial part of the observed group count. General statistical reasoning therefore cautions against drawing broad conclusions from apparent contrasts between groups. The record does not report inferential tests or confidence intervals for these safety counts.
What can confidence intervals and significance tests add?
In general, a confidence interval expresses the range of estimates compatible with the observed data under a stated statistical model. It communicates precision as well as the point estimate. A significance test evaluates data against a specified null hypothesis and assumptions; a p-value is not the probability that a treatment works or that the null hypothesis is true. The registry record does not report confidence intervals, p-values, or statistical tests for the primary safety outcome, so no such inference should be attributed to the posted counts.
The study was not a randomized comparison, and the posted safety values are counts. A formal comparison would require a prespecified question, an appropriate model, and assumptions that account for the design and available data. None of those analysis details is reported in the registry record. The general statistical concepts do not turn the dose groups into a causal comparison.
How should planning calculations be understood?
The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. In general, such calculations explore how many participants might be needed under selected assumptions. They are planning illustrations, not observed results, and do not describe the number of participants actually enrolled in a group. They are not observed power. The registry record does not report that these assumptions were used to design this Phase I study, nor does it report the trial's own sample-size justification.
In general, planning calculations depend on the size of the effect selected, variability, design, and analysis method. If assumptions differ from actual conditions, the planning output may not describe what the trial could detect. The registry record does not report the protocol's underlying design assumptions, a prespecified target effect, or a power calculation for the study. The illustrations should not be read as proof that the study was adequately powered for safety or clinical activity.
What does the registry report about analysis methods?
The primary analysis population is described as all participants who received at least one dose of study treatment. The record lists 50 outcome measures and zero analyses. The detailed statistical analysis plan, methods for handling repeated events, missing observations, and any interim analyses are not reported in the registry record. The secondary outcomes describe pharmacokinetic measures, but estimates for those outcomes are not included in the posted results described in the record.
In general, analysis choices should follow the endpoint and design. Safety summaries often distinguish participants with an event from the total exposed population, while time-to-event analyses account for follow-up and censoring. The posted primary outcome is a participant count, and no time-to-event model is reported. It would therefore be inappropriate to infer a hazard ratio or exposure-adjusted event rate from these counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a broad set of study aims and 50 outcome measures, including safety outcomes and pharmacokinetic measures. When a study evaluates multiple outcomes or makes repeated comparisons, multiplicity can increase the chance of at least one apparently unusual result arising by chance. In general, investigators may address multiplicity through prespecified outcome hierarchies, adjustment procedures, or by treating findings as exploratory. The registry record does not report a multiplicity strategy, a hierarchy for interpreting the outcomes, or which analyses were considered confirmatory.
The record identifies the primary safety outcome and states that the analysis population included all participants who received at least one dose. It does not report a detailed statistical analysis plan, analysis population rules beyond that description, interim analyses, missing-data methods, or procedures for participants with incomplete follow-up. Those details are not reported in the registry record. No assumption should be made about how incomplete observations or multiple events for one participant were handled.
The record lists zero analyses. This means the registry does not provide analysis entries alongside the outcomes; it does not establish that no analysis took place outside the record. Results for clinical activity and the listed pharmacokinetic outcomes are not reported in the registry record. The available safety counts should therefore be treated as descriptive registry results, without assuming that missing outcome estimates were null, favorable, or unfavorable.
For a non-randomized dose-escalation study, multiplicity is not only a question of multiple p-values. Comparing many sequential dose groups can invite selective emphasis on striking counts. Without a prespecified comparison plan and appropriate uncertainty estimates, patterns across doses remain descriptive. The registry record does not report a formal between-dose testing strategy.
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 |
|---|---|---|---|
| Part 1:GSK2816126 50 mg Twice-weekly | 1 | 2 | 50.0% |
| Part 1:GSK2816126 100 mg Twice-weekly | 0 | 1 | 0.0% |
| Part 1:GSK2816126 200 mg Twice-weekly | 0 | 1 | 0.0% |
| Part 1:GSK2816126 400 mg Twice-weekly | 0 | 1 | 0.0% |
| Part 1:GSK2816126 800 mg Twice-weekly | 1 | 3 | 33.3% |
| Part 1:GSK2816126 1200 mg Twice-weekly | 2 | 4 | 50.0% |
| Part 1:GSK2816126 1800 mg Twice-weekly | 1 | 10 | 10.0% |
| Part 1:GSK2816126 2400 mg Twice-weekly | 5 | 12 | 41.7% |
| Part 1:GSK2816126 3000 mg Twice-weekly | 3 | 7 | 42.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part 1:GSK2816126 50 mg Twice-weekly | 1 of 2 |
| Part 1:GSK2816126 100 mg Twice-weekly | 0 of 1 |
| Part 1:GSK2816126 200 mg Twice-weekly | 0 of 1 |
| Part 1:GSK2816126 400 mg Twice-weekly | 0 of 1 |
| Part 1:GSK2816126 800 mg Twice-weekly | 0 of 3 |
| Part 1:GSK2816126 1200 mg Twice-weekly | 1 of 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 |
|---|---|
| Part 1:GSK2816126 50 mg Twice-weekly | 2 of 2 |
| Part 1:GSK2816126 100 mg Twice-weekly | 1 of 1 |
| Part 1:GSK2816126 200 mg Twice-weekly | 1 of 1 |
| Part 1:GSK2816126 400 mg Twice-weekly | 1 of 1 |
| Part 1:GSK2816126 800 mg Twice-weekly | 3 of 3 |
| Part 1:GSK2816126 1200 mg Twice-weekly | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Part 1:GSK2816126 50 mg Twice-weekly | Part 1:GSK2816126 100 mg Twice-weekly | Part 1:GSK2816126 200 mg Twice-weekly | Part 1:GSK2816126 400 mg Twice-weekly | Part 1:GSK2816126 800 mg Twice-weekly | Part 1:GSK2816126 1200 mg Twice-weekly |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 1 of 4 |
| Respiratory tract infection | Infections and infestations | 1 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 0 of 4 |
| Bronchitis | Infections and infestations | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 1 of 4 |
| Campylobacter infection | Infections and infestations | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 1 of 3 | 0 of 4 |
| Enterocolitis | Gastrointestinal disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 1 of 3 | 0 of 4 |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 1 of 3 | 0 of 4 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 0 of 4 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 0 of 4 |
| Hypokalaemia | Metabolism and nutrition disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 0 of 4 |
| Intestinal obstruction | Gastrointestinal disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part 1:GSK2816126 50 mg Twice-weekly | Part 1:GSK2816126 100 mg Twice-weekly | Part 1:GSK2816126 200 mg Twice-weekly | Part 1:GSK2816126 400 mg Twice-weekly | Part 1:GSK2816126 800 mg Twice-weekly | Part 1:GSK2816126 1200 mg Twice-weekly |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 0 of 2 | 1 of 1 | 1 of 1 | 1 of 1 | 2 of 3 | 2 of 4 |
| Nausea | Gastrointestinal disorders | 1 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 2 of 3 | 2 of 4 |
| Vomiting | Gastrointestinal disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 2 of 3 | 2 of 4 |
| Anaemia | Blood and lymphatic system disorders | 0 of 2 | 0 of 1 | 0 of 1 | 1 of 1 | 2 of 3 | 0 of 4 |
| Constipation | Gastrointestinal disorders | 1 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 1 of 3 | 1 of 4 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 2 | 0 of 1 | 1 of 1 | 0 of 1 | 1 of 3 | 0 of 4 |
| Abdominal pain | Gastrointestinal disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 1 of 3 | 2 of 4 |
| Insomnia | Psychiatric disorders | 1 of 2 | 1 of 1 | 0 of 1 | 0 of 1 | 0 of 3 | 1 of 4 |
| Infusion related reaction | Injury, poisoning and procedural complications | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 1 of 3 | 1 of 4 |
| Diarrhoea | Gastrointestinal disorders | 0 of 2 | 0 of 1 | 0 of 1 | 0 of 1 | 1 of 3 | 1 of 4 |
Serious events with the highest arm-level rate: respiratory tract infection (50.0%), campylobacter infection (33.3%), enterocolitis (33.3%), tumour pain (33.3%), pyrexia (25.0%).
Read each dose group's figures as the number of participants at risk and the number of those participants affected, separately for SAEs and non-SAEs. For example, the 2400 mg group lists 12 participants at risk for each category, 5 with an SAE, and 12 with a non-SAE. The 3000 mg group lists 7 at risk, 3 with an SAE, and 7 with a non-SAE. The 50 mg group lists 2 at risk, 1 with an SAE, and 2 with a non-SAE. Other group counts are reported in the same way in the posted results.
Deaths are shown as separate counts by dose group: 1 at 50 mg, 1 at 1200 mg, 2 at 1800 mg, and 1 at 3000 mg; the other Part 1 groups list zero. The registry record does not report the cause of death or whether any death was considered related to treatment. These figures should not be interpreted as causal findings.
The listed serious-event terms include respiratory tract infection at 50.0%, Campylobacter infection, enterocolitis, and tumour pain at 33.3% each, and pyrexia and bronchitis at 25.0% each. The denominator for these percentages is not reported in the registry record. Event terms and participant counts provide different summaries; neither alone establishes treatment attribution.
12. What the Result Does, and Does Not, Mean
The results establish that participants in the listed Part 1 dose groups experienced serious and non-serious adverse events during the study's reported timeframe. They also show the number of deaths listed for each group and identify several serious adverse event terms with registry percentages. These are descriptive observations from a Phase I study, with a primary safety analysis population defined as participants who received at least one dose.
The results do not establish that GSK2816126 caused any particular event. The adverse event definition includes occurrences whether or not considered related to the medicinal product, and the registry does not provide event-level attribution for the posted counts. The death counts alone do not indicate cause or treatment relationship.
The results do not show that one dose is safer or less safe than another. The study was open-label, sequential, and non-randomized, and dose groups differed in size. There is no randomized control group, and the registry record does not report adjusted comparisons, confidence intervals, or statistical tests across dose groups. Descriptive differences are not equivalent to causal effects.
The study's stated aims included pharmacokinetics, pharmacodynamics, clinical activity, and determination of a recommended Phase 2 dose. The registry record does not report estimates for clinical activity or pharmacokinetic outcomes, and does not report the recommended Phase 2 dose. It also lists zero participants at risk in the Part 2 safety group. As a result, the posted safety counts do not answer whether the treatment had clinical activity or what dose was selected for further study.
The record is listed as terminated, but the reason for termination is not reported in the registry record. No conclusion about why the study ended should be drawn from status alone. The available information characterizes reported safety counts; it is not a complete account of the study's conduct or all outcomes.
13. Why This Trial Matters Statistically
Early-phase studies ask questions that differ from those of a large randomized efficacy trial. This study was designed to investigate safety, pharmacokinetics, pharmacodynamics, and clinical activity while escalating dose and planning expansion cohorts. That design makes it useful to distinguish the descriptive purpose of dose-escalation safety summaries from the causal comparisons that randomization can support.
The posted counts also illustrate why denominators matter. The dose groups include different numbers of participants, and some groups are particularly small. The same number of affected participants can have a different descriptive meaning in groups of different sizes, while small group counts remain imprecise. The registry record does not provide uncertainty intervals for the safety comparisons, so the counts should not be treated as precise estimates of risk.
Another statistical distinction is between an event count and a participant count. The primary outcome reports participants with SAEs and non-SAEs, not every event episode or an exposure-adjusted rate. This affects what can be compared and which conclusions can be drawn. The listed deaths and serious event terms add context, but do not identify cause or treatment relatedness.
The study's planned Part 2 expansion and its stated interest in EZH2 status demonstrate that the broader research question included specific disease groups and biological subgroups. The registry record reports no Part 2 participants at risk and does not report clinical activity results. Thus, the record highlights a common challenge in interpreting early-phase registrations: planned objectives and posted outcome data are not always equally complete.
Statistically, the key lesson is to keep design, endpoint, and inference aligned. Sequential safety counts can describe what occurred among treated participants. They cannot substitute for randomized evidence, formal uncertainty estimates, or unreported clinical activity outcomes.
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 most important limitation is the non-randomized, sequential design. Dose groups are not like-for-like control groups, so their outcomes cannot establish the causal effect of dose. The study was open-label and had no masking, and the registry does not report participant or investigator blinding procedures beyond the listed absence of masking.
Group sizes were small and varied, with only 1 participant listed in each of the 100 mg, 200 mg, and 400 mg groups and 12 in the 2400 mg group. Small groups make descriptive findings sensitive to individual participants. The record does not provide confidence intervals or inferential tests for the primary safety counts.
The primary outcome records participants with events over a timeframe of up to 3.2 years, but group-specific follow-up and exposure duration are not reported in the registry record. Counts therefore do not adjust for time at risk. Detailed event severity, timing, recurrence, and treatment relatedness are also not reported in the registry record. The denominator and calculation method for the listed serious event term percentages are not reported in the registry record.
Although the study planned Part 2 expansion cohorts, the Part 2 safety group reports zero participants at risk. Clinical activity and pharmacokinetic results are not reported in the registry record, nor is the recommended Phase 2 dose. The study is listed as terminated, but the reason is not reported in the registry record. The statistical analysis plan, missing-data procedures, interim analyses, and sample-size justification are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2816126 in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma, Transformed Follicular Lymphoma, Other Non-Hodgkin's Lymphomas, Solid Tumors and Multiple Myeloma — NCT02082977.
- Registry record last updated 2020-02-25; status last verified 2020-02.
- Results first posted 2019-06-28.
- 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
NCT02082977 is a Phase I, open-label, multicenter study of GSK2816126 in relapsed or refractory lymphoma, other non-Hodgkin's lymphomas, solid tumors, and multiple myeloma. Part 1 used sequential twice-weekly intravenous dose groups from 50 mg to 3000 mg; Part 2 was planned as an expansion at the recommended Phase 2 dose. Enrollment was 41. The study started on 2014-04-24, had a primary completion date of 2017-06-20, and is listed as terminated.
The primary outcome counts participants with serious and non-serious adverse events, among participants who received at least one dose. Posted counts are available across the Part 1 dose groups, while the Part 2 safety group lists zero participants at risk. The registry record does not report clinical activity results, the recommended Phase 2 dose, or the reason for termination. The non-randomized, sequential design means safety counts are descriptive and do not provide a controlled comparison between doses.