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 BGB-290 and Temozolomide in Treating Patients With Recurrent Gliomas With IDH1/2 Mutations (NCT03914742), a non-randomized phase 1, phase 2 study. The primary outcome is Phase II: Overall Best Response Rate for Arm A and Arm B.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03914742 |
| Phase | Phase 1, Phase 2 |
| Condition | IDH1 Mutation, IDH2 Mutation, Recurrent Glioblastoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 67 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
| Results posted | Yes |
2. Clinical Question
Population
People with recurrent gliomas carrying IDH1 or IDH2 mutations. The record describes Phase I dose finding for recurrent grade II–III glioma, Phase II groups defined by prior alkylator treatment, an exploratory GBM group, and a surgical group eligible for re-resection. The registry lists an enrollment of 67.
Intervention
The main drug combination is BGB-290 with temozolomide. The dose-finding group used BGB-290 with a starting temozolomide schedule that could be de-escalated if necessary. Phase II treatment used the dose combination established in Phase I. The GBM and surgical groups had separately described BGB-290 schedules.
Comparator
There is no randomized comparator. The allocation is non-randomized and the model is single-group. Arm A and Arm B are treatment groups defined by previous alkylator treatment, not control arms assigned to different therapies. Their outcomes therefore do not form a like-for-like randomized comparison.
Primary question
The primary Phase II outcome asks how many participants in Arm A and Arm B had an overall best response under Response Assessment in Neuro-oncology criteria, up to 2 years. The registry record does not report the response counts or an analysis comparing the arms.
The clinical question combines an early-phase assessment of treatment and dose with a later assessment of response in recurrent, IDH1/2-mutant glioma. Arm A is described as alkylator-resistant: participants had failed temozolomide and another alkylator. Arm B is described as not alkylator-resistant: participants had failed temozolomide or another alkylator, with at least 12 months since last treatment. These definitions distinguish clinical histories; they do not create randomized comparison groups.
The record also includes an exploratory grade IV GBM group and a surgical group. Those groups have distinct descriptions and schedules, so their role should not be conflated with the primary Phase II response question in Arms A and B. Response results for any group are not reported in the registry record.
3. Trial Design
This is a Phase I/II, non-randomized, unmasked, single-group study sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. It is listed as completed, with an enrollment of 67. The registry lists a start date of 2020-02-16 and a primary completion date of 2023-10-31. The study concerns BGB-290 and temozolomide in recurrent gliomas with IDH1/2 mutations.
Phase I is described as dose finding for recurrent IDH1/2-mutant grade II–III glioma. BGB-290 was described at 60 mg by mouth twice daily on days 1-28, with temozolomide at a 20 mg once-daily starting dose on days 1-28. The temozolomide schedule could be de-escalated to days 1-21, days 1-14, or days 1-7 if necessary, while BGB-290 was held constant at 60 mg by mouth twice daily. The record does not report the dose-finding results or the rationale for any schedule changes.
Phase II includes Arm A, for grade II–III recurrent glioma after failure of temozolomide and another alkylator, and Arm B, for grade II–III recurrent glioma after failure of temozolomide or another alkylator, with at least 12 months since last treatment. Both are described as receiving the dose combination established in Phase I. The registry also lists an exploratory GBM group treated with BGB-290 before surgery and a surgical group receiving BGB-290 around re-resection.
Because allocation is non-randomized and there is no masking, the study does not provide a randomized blinded comparison. The record does not report a control group, a sample-size justification, or further details of allocation. The protocol and analysis plan beyond the registry descriptions 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: 67 patients signed consent, however, 1 patient in the Phase 1 Dose Finding, never started treatment before they withdrew, hence 66 evaluable patients.
Overall Study
| Stage | Phase 1: Dose Finding | Phase 2: Arm A Alkylator-resistant | Phase 2: Arm B NOT Alkylator-resistant | GBM Arm | Surgical Arm |
|---|---|---|---|---|---|
| STARTED | 7 | 15 | 24 | 10 | 10 |
| COMPLETED | 7 | 15 | 24 | 10 | 10 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
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: In the Phase 1: Dose Finding arm, 8 patients signed consent, however 1 patient withdrew prior to starting treatment. Hence a total of 7 patients evaluable for the Phase 1 portion of the study
| Characteristic | Unit | Phase 1: Dose Finding | Phase 2: Arm A Alkylator-resistant | Phase 2: Arm B NOT Alkylator-resistant | GBM Arm | Surgical Arm | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 7 | 15 | 24 | 10 | 10 | 66 | |
| Age, Continuous | years | 45.2 (25.4 to 54.6) | 42.7 (35.9 to 58.4) | 45.5 (22.2 to 68.6) | 35.9 (23.5 to 72.9) | 46.7 (32.8 to 66.9) | 44.5 (22.2 to 72.9) |
| Sex: Female, Male: Female | Participants | 3 | 5 | 12 | 5 | 4 | 29 |
| Sex: Female, Male: Male | Participants | 4 | 10 | 12 | 5 | 6 | 37 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 2 | 1 | 0 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 0 | 0 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 6 | 12 | 21 | 7 | 8 | 54 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 2 | 1 | 2 | 1 | 6 |
| Number of Relapes | relapses | 3 (1 to 4) | 2 (2 to 3) | 1 (1 to 3) | 2 (1 to 7) | 2 (1 to 2) | 1 (1 to 7) |
| Molecular Markers (1p/19q): Co-deleted | Participants | 2 | 9 | 18 | 1 | 3 | 33 |
| Molecular Markers (1p/19q): intact | Participants | 4 | 5 | 5 | 8 | 7 | 29 |
| Molecular Markers (1p/19q): 19q-deleted only | Participants | 1 | 0 | 1 | 1 | 0 | 3 |
| Molecular Markers (1p/19q): Not Done | Participants | 0 | 1 | 0 | 0 | 0 | 1 |
| MGMT gene (Methylated) | Participants | 1 | 9 | 19 | 6 | 5 | 40 |
| Type of Surgical Proceedure: Gross Total Resection | Participants | 4 | 9 | 9 | 7 | 5 | 34 |
| Type of Surgical Proceedure: Subtotal Resection | Participants | 2 | 6 | 14 | 2 | 4 | 28 |
| Type of Surgical Proceedure: Biopsy | Participants | 1 | 0 | 1 | 1 | 1 | 4 |
| Karnosky Performance Status (KPS) | units on a scale | 90 (70 to 100) | 80 (70 to 100) | 90 (60 to 100) | 90 (70 to 100) | 90 (60 to 100) | 90 (60 to 100) |
6. Primary Endpoint
The registry lists the primary outcome as Phase II: Overall Best Response Rate for Arm A and Arm B, measured over up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants in Phase II Arm A and Arm B with an overall best response, assessed up to 2 years using Response Assessment in Neuro-oncology (RANO) criteria. It is a count endpoint: it records how many participants met a response category, rather than measuring the amount of tumor change as a continuous value. The registry defines complete response, partial response, stable disease, and progressive disease using imaging features, corticosteroid use, new lesions, and clinical status.
Under the registry definition, complete response requires no change in T1-gadolinium-enhancing disease, stable or reduced T2/FLAIR signal, no new lesion, no corticosteroid use, and stable or improved clinical status. Partial response requires at least 50% change in the size of T1-gadolinium-enhancing disease, with the other listed imaging and clinical conditions. Stable disease is defined by less than 50% reduction to less than 25% increase in the size of that disease, with the stated conditions on T2/FLAIR signal, new lesions, corticosteroid use, and clinical status. Progressive disease includes at least 25% increase in size, increased T2/FLAIR signal, a new lesion, or worsening clinical status.
A best-response endpoint gives a categorical summary of the strongest response classification recorded during the stated assessment period. It is used to describe tumor response under prespecified criteria, but its interpretation depends on the assessment rules and the number of participants evaluable for response. The registry record does not report the response counts, the denominator used for the endpoint, or how missing or unevaluable assessments were handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies overall best response in Phase II Arm A and Arm B as the primary endpoint, but it does not report the response counts or an estimated response rate. It also does not report confidence intervals, a p-value, or a statistical comparison of the two arms. Consequently, the posted results do not establish the size or precision of any response finding. A result cannot be inferred from the endpoint definition, study completion status, or adverse-event counts.
Arm A and Arm B differ according to prior alkylator treatment. Arm A is described as having failed temozolomide and another alkylator; Arm B as having failed temozolomide or another alkylator, with at least 12 months since last treatment. These histories may be relevant to clinical context, but allocation is non-randomized. Any difference between groups could reflect differences in the participants or their prior treatment histories, rather than a treatment effect. The registry explicitly does not present the arms as a like-for-like control comparison.
The overall enrollment listed is 67, but that figure does not establish how many participants contributed to the primary endpoint or to each group. The record separates participants into Phase I, Phase II, GBM, and surgical groups, and does not give an endpoint-specific analysis population or denominators. It is therefore not possible to derive response proportions from the enrollment figure. No counts should be interpreted as rates without the relevant denominator and outcome definition.
The record lists progression-free survival, overall survival, and duration of response as secondary outcomes. It does not report their estimates or analysis details. Without the posted outcome results, follow-up summaries, and uncertainty measures, the precision and direction of those outcomes cannot be assessed. The scheduled timeframe for the primary response outcome is up to 2 years, but that alone does not show the duration of follow-up achieved for each participant.
The adverse-event record lists serious adverse events and other adverse events by study group, along with deaths. These are descriptive safety counts. They do not by themselves establish that an event or death was caused by BGB-290 or temozolomide, and they do not compare treatment with an untreated or alternative-treatment group. Overall, the registry record supplies a study framework and safety counts but not the efficacy analyses needed to quantify response or its uncertainty.
9. Statistical Methods Explained
What does a count endpoint represent?
The primary outcome is expressed as the number of participants with an overall best response in each of the two Phase II groups. Such a count is a direct tally, but its meaning depends on the population counted and the rule used to classify outcomes. A count alone is not a response rate: interpreting it as a proportion requires a denominator, such as the number assessed or the number treated, and a clear rule for handling participants without an evaluable assessment. Neither endpoint-specific denominator nor missing-assessment method is reported in the registry record.
The categories are based on RANO criteria, combining imaging findings with clinical status and corticosteroid use. This matters because response is not defined by a change in a single measurement alone. The registry states thresholds for changes in T1-gadolinium-enhancing disease and also includes T2/FLAIR signal, new lesions, corticosteroid use, and clinical status. The registry record does not provide further detail on how the criteria were operationalized or adjudicated.
How should uncertainty be understood?
General statistical explanation: an estimate describes the observed data, while a confidence interval describes the range of values reasonably compatible with those data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval. For a response proportion, precision depends on the event count and the denominator, as well as the interval method. The registry record does not report response estimates or confidence intervals, so their precision cannot be evaluated.
A p-value, when reported, assesses how compatible data are with a specified null hypothesis under the chosen model. It does not measure the size or clinical importance of an effect, and it does not establish causation. No p-value or inferential analysis for the primary response endpoint is reported in the registry record. The record lists zero analyses, so there is no registry-reported analysis output to interpret.
What does the design allow?
The study is non-randomized, unmasked, and described as single-group. Randomization can help balance measured and unmeasured characteristics between treatment groups, while masking can reduce some assessment and behavior-related biases. Those features are not part of the design recorded. Arm A and Arm B are differentiated by prior treatment history, not randomly assigned treatment. Comparisons between them would therefore be observational and potentially confounded. The record does not report an adjusted comparison or a statistical plan for such comparisons.
Phase I dose finding and Phase II response assessment address different questions. Dose finding concerns the treatment schedule, whereas the primary Phase II endpoint concerns best response in Arm A and Arm B. The registry describes the temozolomide schedule as subject to de-escalation if necessary and says the Phase II combination uses a dose established in Phase I. The process used to select that dose and the dose-finding analysis are not reported in the registry record.
How should planning illustrations be read?
General statistical explanation: a sample-size calculation is a planning exercise under stated assumptions, not a summary of what happened in a completed study. The registry's planning illustration is based on an observed effect and specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers detection of a stated fraction of the observed effect. The illustration is not the trial's own design justification, and it is not observed power. The registry record does not report the actual sample-size justification or the observed effect magnitude required to assess the illustration's assumptions.
The illustration uses participants per arm for 80% power for non-time-to-event outcomes; time-to-event illustrations are described as total events using the Schoenfeld method. Such calculations depend on assumptions and should not be read as evidence that a target was achieved or that an observed treatment effect is reliable. No calculated planning values are reported in the registry record. The actual trial enrollment and the illustration's hypothetical planning quantities answer different questions.
What is not documented?
Several analysis details needed for fuller statistical interpretation are not reported in the registry record: the primary endpoint denominator, analysis population, missing-data method, confidence-interval method, hypothesis tests, adjustment for multiple outcomes, and handling of participants with no evaluable response. The specific timing and frequency of assessments are also not reported beyond the primary outcome timeframe of up to 2 years. The registry lists progression-free survival, overall survival, and duration of response as secondary outcomes, but does not provide the analysis methods or results for them.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome for Phase II: overall best response in Arm A and Arm B. It also names progression-free survival in Arm A and Arm B, overall survival in Arm A and Arm B, and duration of response as secondary outcomes. The record does not describe a hierarchy among outcomes, a multiplicity adjustment, or how inferential claims across outcomes would be controlled. Any such strategy is not reported in the registry record.
Missing-data handling is also not reported. In a response analysis, participants may lack an evaluable assessment or may not have a classification recorded for other reasons. The approach to those cases can affect the denominator and the resulting estimate. The registry record does not state whether participants without an evaluable response were excluded, classified in a particular category, or handled in another way.
The analysis population for the primary endpoint is not reported in the registry record. The listed enrollment of 67 does not identify the number included in the Phase II response analysis, and it should not be treated as the denominator for either arm. The record does not state whether analyses used all enrolled participants, participants who began treatment, or another defined population.
The registry lists zero analyses. It therefore does not report an analysis plan, endpoint estimates, or inferential results to review for multiplicity or missing-data assumptions. These absences limit the interpretation of both the primary response question and the secondary outcomes; they do not imply that a particular analysis method was or was not used outside the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Phase 1: Dose Finding | 1 | 7 | 14.3% |
| Phase 2: Arm A Alkylator-resistant | 0 | 15 | 0.0% |
| Phase 2: Arm B NOT Alkylator-resistant | 2 | 24 | 8.3% |
| GBM Arm | 1 | 10 | 10.0% |
| Surgical Arm | 3 | 10 | 30.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase 1: Dose Finding | 4 of 7 |
| Phase 2: Arm A Alkylator-resistant | 4 of 15 |
| Phase 2: Arm B NOT Alkylator-resistant | 6 of 24 |
| GBM Arm | 6 of 10 |
| Surgical Arm | 3 of 10 |
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 |
|---|---|
| Phase 1: Dose Finding | 7 of 7 |
| Phase 2: Arm A Alkylator-resistant | 15 of 15 |
| Phase 2: Arm B NOT Alkylator-resistant | 24 of 24 |
| GBM Arm | 10 of 10 |
| Surgical Arm | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase 1: Dose Finding | Phase 2: Arm A Alkylator-resistant | Phase 2: Arm B NOT Alkylator-resistant | GBM Arm | Surgical Arm |
|---|---|---|---|---|---|---|
| Neutrophile count decrease | Investigations | 1 of 7 | 0 of 15 | 0 of 24 | 0 of 10 | 2 of 10 |
| Platelet count decrease | Investigations | 1 of 7 | 0 of 15 | 0 of 24 | 0 of 10 | 2 of 10 |
| White Blood Cell Count Decrease | Investigations | 1 of 7 | 0 of 15 | 0 of 24 | 0 of 10 | 2 of 10 |
| Lymphocyte count decrease | Investigations | 0 of 7 | 0 of 15 | 0 of 24 | 0 of 10 | 2 of 10 |
| Acute Kidney Injury | Renal and urinary disorders | 0 of 7 | 0 of 15 | 0 of 24 | 0 of 10 | 1 of 10 |
| Alanine aminotransferase increase | Investigations | 0 of 7 | 0 of 15 | 0 of 24 | 1 of 10 | 0 of 10 |
| Anemia | Blood and lymphatic system disorders | 0 of 7 | 0 of 15 | 0 of 24 | 0 of 10 | 1 of 10 |
| Dehydration | Metabolism and nutrition disorders | 0 of 7 | 0 of 15 | 1 of 24 | 0 of 10 | 0 of 10 |
| headache | Nervous system disorders | 0 of 7 | 0 of 15 | 1 of 24 | 0 of 10 | 0 of 10 |
| intracranial hemorrhage | Nervous system disorders | 0 of 7 | 0 of 15 | 0 of 24 | 0 of 10 | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase 1: Dose Finding | Phase 2: Arm A Alkylator-resistant | Phase 2: Arm B NOT Alkylator-resistant | GBM Arm | Surgical Arm |
|---|---|---|---|---|---|---|
| anemia | Blood and lymphatic system disorders | 3 of 7 | 11 of 15 | 20 of 24 | 8 of 10 | 7 of 10 |
| White blood cell decreased | Investigations | 4 of 7 | 9 of 15 | 18 of 24 | 7 of 10 | 6 of 10 |
| Neutrophil count decreased | Investigations | 4 of 7 | 8 of 15 | 17 of 24 | 6 of 10 | 5 of 10 |
| Platelet count decreased | Investigations | 2 of 7 | 8 of 15 | 16 of 24 | 8 of 10 | 6 of 10 |
| Fatigue | General disorders | 4 of 7 | 10 of 15 | 14 of 24 | 3 of 10 | 3 of 10 |
| Lymphocyte count decreased | Investigations | 4 of 7 | 4 of 15 | 13 of 24 | 4 of 10 | 4 of 10 |
| Nausea | Gastrointestinal disorders | 3 of 7 | 2 of 15 | 16 of 24 | 3 of 10 | 4 of 10 |
| Alanine aminotransferase increase | Investigations | 1 of 7 | 3 of 15 | 6 of 24 | 3 of 10 | 1 of 10 |
| Aspartate aminotransferase increased | Investigations | 1 of 7 | 2 of 15 | 3 of 24 | 3 of 10 | 0 of 10 |
| Constipation | Gastrointestinal disorders | 1 of 7 | 3 of 15 | 3 of 24 | 1 of 10 | 1 of 10 |
Serious events with the highest arm-level rate: lymphocyte count decrease (20.0%), neutrophile count decrease (20.0%), platelet count decrease (20.0%), white blood cell count decrease (20.0%), acute kidney injury (10.0%).
The registry lists serious adverse events, other adverse events, and deaths separately for each study group. In Phase I: Dose Finding, 1 of 7 participants at risk had a serious adverse event, 7 of 7 had other adverse events, and 4 deaths are listed. In Phase II: Arm A Alkylator-resistant, 0 of 15 had a serious adverse event, 15 of 15 had other adverse events, and 4 deaths are listed. In Phase II: Arm B NOT Alkylator-resistant, 2 of 24 had a serious adverse event, 24 of 24 had other adverse events, and 6 deaths are listed. In the GBM Arm, 1 of 10 had a serious adverse event, 10 of 10 had other adverse events, and 6 deaths are listed. In the Surgical Arm, 3 of 10 had a serious adverse event, 10 of 10 had other adverse events, and 3 deaths are listed.
The listed serious-event terms include lymphocyte count decrease, neutrophile count decrease, platelet count decrease, and white blood cell count decrease, each at 20.0%; acute kidney injury and alanine aminotransferase increase are each listed at 10.0%. These are registry-listed terms and percentages. The record does not clarify the denominator or detailed coding context for these term percentages.
These are descriptive counts, not comparisons against a control group. The listed deaths do not establish cause of death or treatment attribution. The registry record does not provide further detail on event timing, duration, severity grading beyond the serious-event designation, or causality assessment.
12. What the Result Does, and Does Not, Mean
The registry describes a completed Phase I/II study of BGB-290 with temozolomide in recurrent gliomas with IDH1/2 mutations. Its primary Phase II outcome is overall best response in Arm A and Arm B, defined with RANO response categories and assessed up to 2 years. The record also describes dose-finding, an exploratory GBM group, a surgical group, secondary outcomes, and adverse-event counts.
What the record does not establish is the magnitude or precision of response. It does not report primary response counts, response proportions, confidence intervals, or an inferential comparison. It also does not report results for the listed secondary outcomes. The study's enrollment and completion status cannot substitute for these outcome data, and the endpoint definitions do not show how participants actually responded.
Because the trial is non-randomized and single-group, the registry does not support a randomized comparison of the combination against another treatment or against no treatment. Arm A and Arm B reflect prior alkylator-treatment histories and are not like-for-like randomized control arms. Differences between those groups, if reported elsewhere, would require cautious interpretation because group membership may be associated with other prognostic differences.
The safety counts describe events recorded within the study groups. They do not, on their own, establish that BGB-290 or temozolomide caused those events or the listed deaths. Nor do they provide a comparison with another regimen. The record does not give enough information to assess event timing, attribution, or the statistical uncertainty around safety frequencies.
In short, the registry record documents the study design, outcome definitions, and group-level safety counts, but the efficacy results and analysis details are not reported in the registry record. Conclusions about response, survival, comparative effects, or the precision of any estimated effect cannot be drawn from these registry entries alone.
13. Why This Trial Matters Statistically
This study addresses an early-phase and clinically specific research question: a combination of BGB-290 and temozolomide in recurrent gliomas with IDH1/2 mutations. The registry distinguishes groups by grade and prior treatment history, including alkylator-resistant and not alkylator-resistant Phase II groups. That distinction makes clear why study populations and prior therapy matter when interpreting outcomes: the groups represent different clinical histories, rather than interchangeable treatment arms.
Statistically, the record is a useful example of the difference between an endpoint definition and an endpoint result. It defines overall best response using RANO criteria, including imaging and clinical features, but does not report the response counts or their denominators. Without those results, no response proportion or uncertainty can be assessed. An outcome can be clearly specified in a registry and still be unavailable for statistical interpretation there.
The design also illustrates the limits of uncontrolled evidence. A single-group, non-randomized study can document treatment experience and generate information for subsequent research, but it does not provide the protection against confounding that random assignment can offer. Arm A and Arm B are defined by prior alkylator treatment, so their contrast is not a randomized treatment-effect estimate.
Finally, the record separates safety descriptions across Phase I, Phase II, exploratory GBM, and surgical groups. Keeping those groups distinct is important because their treatment context and participant characteristics differ. The registry's safety counts are informative as descriptive listings, while their interpretation remains bounded by the absence of a control comparison and limited reporting on attribution and analysis methods.
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.
Several limitations are specific to the information recorded for this trial. The primary outcome is named and its RANO definitions are detailed, but response counts, endpoint denominators, estimates, and confidence intervals are not reported in the registry record. The listed enrollment of 67 does not show how many participants were analyzed in Phase II Arm A or Arm B, nor how many were assessed for response.
The non-randomized, single-group design does not provide a randomized control comparison. Arm A and Arm B are distinguished by previous alkylator treatment and time since last treatment, so their results would not necessarily be directly comparable even if outcome estimates were available. The record does not report adjusted analyses that might address measured differences between groups.
The study contains several distinct components: Phase I dose finding, Phase II groups, an exploratory GBM group, and a surgical group. The registry does not report how the overall enrollment was distributed for each analysis or how findings across these components were integrated. The dose-finding decision process and the rationale for the planned schedule are not reported in the registry record.
Details needed to assess outcome completeness and analytic robustness are also absent. The record does not report the analysis population, missing-data method, multiplicity strategy, statistical test, or confidence-interval method. Secondary outcome results and analysis methods are not reported either.
Safety information is presented as group-level counts, but event attribution, timing, and detailed coding context are not reported. Death counts are listed without information that would establish cause or treatment relationship. These limitations constrain what can be concluded from the registry record; they do not establish that omitted analyses or procedures were absent from the study itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BGB-290 and Temozolomide in Treating Patients With Recurrent Gliomas With IDH1/2 Mutations — NCT03914742.
- Registry record last updated 2025-01-14; status last verified 2025-01.
- Results first posted 2024-12-16.
- 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
NCT03914742 is a completed, non-randomized, unmasked Phase I/II study of BGB-290 with temozolomide in recurrent gliomas with IDH1/2 mutations. The registry lists an enrollment of 67 and a single-group model. Phase I is described as dose finding; Phase II includes alkylator-resistant and not alkylator-resistant groups, with additional exploratory GBM and surgical groups.
The primary Phase II outcome is the number of participants in Arm A and Arm B with overall best response by RANO criteria, assessed up to 2 years. Progression-free survival, overall survival, and duration of response are listed as secondary outcomes. Primary and secondary outcome results, endpoint denominators, and analysis methods are not reported in the registry record.
Group-level serious adverse-event counts, other adverse-event counts, deaths, and selected serious-event terms are listed. The record does not establish treatment causation or provide a randomized control comparison.