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 Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors (NCT04249843), a non-randomized phase 1 study. The primary outcome is Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04249843 |
| Phase | Phase 1 |
| Condition | Solid Tumor, B-Raf Mutation-Related Tumors |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 109 |
| Arms in the primary outcome | n/a |
| Lead sponsor | MapKure, LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced or refractory solid tumors, including molecularly defined tumor subsets. In Phase 1b Group 1, participants had BRAF V600-mutated solid tumors, excluding colorectal cancer, and had progressed on prior BRAF and/or MEK inhibition. Group 2 included advanced solid tumors with BRAF Class II mutations or a BRAF fusion mutation.
Intervention
Brimarafenib, an investigational oral RAF dimer inhibitor. Phase 1a evaluated dose levels from 5 mg to 60 mg. Phase 1b included groups treated with 25 mg or 40 mg once daily, with some 40 mg participants described as randomized and others as non-randomized.
Comparator
No control treatment is identified in the registry record. The overall allocation is marked non-randomized. Although some Phase 1b arm descriptions use the word randomized, the posted record does not present a like-for-like control comparison.
Primary question
In Phase 1a, how many participants in the safety population experienced treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) during treatment and through 30 days after the last dose? The study also evaluated pharmacokinetics and preliminary antitumor activity, but corresponding outcome analyses are not reported in the registry record.
This was a first-in-human Phase 1a/1b study of brimarafenib in participants with advanced or refractory tumors. The early dose-escalation component focused on safety and tolerability, with dose selection informed by that evaluation. The expansion component examined activity in tumor subsets defined by molecular features. These are different objectives: safety counts describe the number of participants with events, while antitumor activity requires outcomes such as response or disease control. The registry lists response-related and time-to-event outcomes among its secondary outcomes, but numerical analyses for those outcomes are not reported in the registry record. The central question that can be addressed from the posted results is therefore descriptive: what adverse-event counts were recorded across the listed treatment groups, and how should those counts be interpreted given the study's design and the absence of a control treatment?
3. Trial Design
The registry describes a Phase 1a/1b, open-label study with sequential modeling, non-randomized overall allocation, and no masking. The study evaluated brimarafenib in participants with advanced or refractory tumors. Enrollment was 109, and the study status is terminated. The recorded start date is 2020-02-10 and the primary completion date is 2025-08-08.
Phase 1a was a dose-escalation component. Participants received brimarafenib at 5 mg, 10 mg, 15 mg, 25 mg, 40 mg, or 60 mg. The arm descriptions specify an oral dose on Day 1, followed by daily dosing from Day 4 onwards. Treatment continued until disease progression, unacceptable toxicity, or study completion. The stated purpose of dose escalation was to evaluate safety and tolerability and inform dose selection.
Phase 1b included expansion groups defined by tumor characteristics and prior treatment. Group 1 enrolled participants with BRAF V600-mutated solid tumors, excluding colorectal cancer, who had progressed on prior BRAF and/or MEK inhibition. The registry lists 25 mg and 40 mg groups, including a 40 mg group labeled randomized and a separate 40 mg group labeled non-randomized. Group 2 included participants with advanced solid tumors harboring BRAF Class II mutations or a BRAF fusion mutation, treated with 40 mg once daily.
The record's overall allocation is marked non-randomized, and its listed comparison warning states that the arms are not a like-for-like control comparison. The presence of randomized wording in some arm descriptions is not reconciled with the overall allocation classification in the registry record. No protocol details explaining this distinction are reported in the registry record. Open-label means treatment masking was not used; the record lists masking as none. The trial's termination reason is not reported in the registry record. A detailed account of recruitment by arm, treatment exposure, and follow-up for each outcome is not reported in the registry record.
The design is suited to describing safety and exploring activity across dose levels and selected tumor subsets, but it does not establish a treatment contrast against a control group in the posted results. The registry lists 22 outcome measures, while the number of posted analyses is 0. Thus, the available numerical findings are the listed safety counts rather than a complete set of analyzed outcomes.
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: Participants in Phase 1a were enrolled sequentially in cohorts of increasing doses of brimarafenib. In Phase 1b, participants in Group 1 who enrolled under Protocol Amendment 6 or 7 (from 17 Apr 2023) were randomized equally to receive 25 mg or 40 mg brimarafenib; participants enrolled prior to Protocol Amendment 6 were assigned to receive 40 mg brimarafenib in a non-randomized fashion. In Phase 1b Group 2, participants were assigned to receive 40 mg brimarafenib.
Only the first 6 of 10 groups are shown.
Overall Study
| Stage | Phase 1a: Brimarafenib 5 mg | Phase 1a: Brimarafenib 10 mg | Phase 1a: Brimarafenib 15 mg | Phase 1a: Brimarafenib 25 mg | Phase 1a: Brimarafenib 40 mg | Phase 1a: Brimarafenib 60 mg |
|---|---|---|---|---|---|---|
| STARTED | 4 | 12 | 7 | 7 | 8 | 4 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 12 | 7 | 7 | 8 | 4 |
Reasons for not completing this period:
| Reason | Phase 1a: Brimarafenib 5 mg | Phase 1a: Brimarafenib 10 mg | Phase 1a: Brimarafenib 15 mg | Phase 1a: Brimarafenib 25 mg | Phase 1a: Brimarafenib 40 mg | Phase 1a: Brimarafenib 60 mg |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 0 | 3 | 2 | 4 | 3 | 0 |
| Adverse Event | 0 | 0 | 1 | 0 | 0 | 2 |
| Death | 2 | 5 | 2 | 2 | 3 | 2 |
| Lost to Follow-up | 0 | 1 | 0 | 0 | 1 | 0 |
| Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Progressive Disease | 2 | 2 | 2 | 1 | 1 | 0 |
| Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety 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: The Safety Population included all participants who received at least one dose of study drug.
Only the first 6 of 11 groups are shown.
| Characteristic | Unit | Phase 1a: Brimarafenib 5 mg | Phase 1a: Brimarafenib 10 mg | Phase 1a: Brimarafenib 15 mg | Phase 1a: Brimarafenib 25 mg | Phase 1a: Brimarafenib 40 mg | Phase 1a: Brimarafenib 60 mg |
|---|---|---|---|---|---|---|---|
| Participants analysed | 4 | 12 | 7 | 7 | 8 | 4 | |
| Age, Continuous | years | 65.8 (SD 12.9) | 51.8 (SD 16.3) | 57.7 (SD 10.1) | 65.6 (SD 10.0) | 59.0 (SD 11.8) | 65.0 (SD 10.3) |
| Sex: Female, Male: Female | Participants | 2 | 6 | 4 | 2 | 3 | 2 |
| Sex: Female, Male: Male | Participants | 2 | 6 | 3 | 5 | 5 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 0 | 0 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 11 | 6 | 7 | 6 | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 | 0 | 2 | 0 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 0 | 0 | 1 | 0 | 0 |
| Race/Ethnicity, Customized: Black or African American | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Native Hawaiian or other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White | Participants | 4 | 10 | 6 | 6 | 7 | 3 |
| Race/Ethnicity, Customized: Multiple | Participants | 0 | 1 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Not Reported/Unknown | Participants | 0 | 1 | 1 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Missing | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 0 | 6 | 5 | 5 | 5 | 3 |
| Region of Enrollment: Australia | participants | 4 | 6 | 2 | 2 | 3 | 1 |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 (fully Active) | Participants | 2 | 7 | 3 | 5 | 3 | 3 |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status: 1 (Limited strenuous activity; light work possible) | Participants | 1 | 5 | 4 | 2 | 5 | 1 |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status: Missing | Participants | 1 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over From first dose up to 30 days after the last dose of study treatment. Maximum treatment duration was 47 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 in the Phase 1a safety population who experienced treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). The registry defines the observation period as from the first dose through 30 days after the last dose of study treatment. It also reports a maximum treatment duration of 47 months.
An event count is a descriptive safety measure: it indicates how many participants in a group had at least one event of the specified type during the defined period. The SAE definition in the registry includes events that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability, or were considered important medical events. These categories describe seriousness, not necessarily whether an event was caused by the study treatment. The posted counts do not establish causation.
Safety endpoints are important in an early-phase study because the treatment and dose levels are being evaluated in participants with advanced or refractory tumors. Counts can identify the observed burden of events in the groups studied and help characterize what was recorded during exposure and follow-up. They are not, on their own, estimates of comparative risk: the record does not provide a control-treatment group for a like-for-like comparison, and the group sizes vary.
Counts also do not convey all clinically relevant detail. They do not show event timing, duration, recurrence, severity apart from the SAE classification, or the number of events per participant. Those details are not reported in the registry record. The endpoint is limited to Phase 1a in its title, although adverse-event counts are also posted for the listed Phase 1b groups. Analyses that combine or compare these components are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results give participant counts by treatment group. In Phase 1a, the SAE counts are 2 of 4 at 5 mg, 8 of 12 at 10 mg, 5 of 7 at 15 mg, 3 of 7 at 25 mg, 5 of 8 at 40 mg, and 4 of 4 at 60 mg. The counts for participants with other adverse events are 4 of 4, 12 of 12, 7 of 7, 7 of 7, 8 of 8, and 4 of 4, respectively. These figures are descriptive observations in small, dose-specific groups; they are not a randomized comparison of doses.
For the Phase 1b groups, the SAE counts are 8 of 13 in Group 1 at 25 mg, 6 of 14 in Group 1 at 40 mg labeled randomized, 4 of 6 in Group 1 at 40 mg labeled non-randomized, and 30 of 34 in Group 2 at 40 mg. The corresponding counts for other adverse events are 12 of 13, 14 of 14, 6 of 6, and 34 of 34. The groups differ in tumor characteristics and, for Group 1, in prior treatment criteria. Their counts should not be read as direct comparisons of dose or treatment effect.
The registry also lists deaths by group: 2, 5, 2, 2, 3, and 2 across the Phase 1a dose groups; 3, 5, 1, and 19 across the four Phase 1b groups. These are counts, not determinations of cause or treatment relatedness. Whether a death was related to brimarafenib is not reported in the registry record.
Several serious-event terms are listed with percentages: Pneumonia, 33.3%; Small intestinal obstruction, 28.6%; Abdominal pain, 25.0%; Intestinal obstruction, 25.0%; Pyrexia, 25.0%; and Atrial fibrillation, 25.0%. The registry record does not provide the event-level counts or denominators for these listed percentages in the posted information, so their precision and basis cannot be assessed from the record alone.
No confidence intervals, hypothesis tests, adjusted estimates, or outcome analysis records are posted; the number of analyses is 0. Consequently, the observed counts should be read as descriptive results, not as estimates of a causal effect or evidence of a statistically established difference. The registry's enrollment of 109 refers to the study overall; it should not be treated as the denominator for each safety group. Group-specific counts and the stated safety population are the relevant context for the posted adverse-event figures.
9. Statistical Methods Explained
The registry presents the primary safety outcome as a count of participants with events. This is a binary outcome at the participant level: each participant either had at least one event of the specified kind during the outcome window or did not. General statistical explanation: binary outcomes are commonly summarized with the number of participants affected and the number assessed. The counts allow readers to see the scale of the observed experience in each group, but they do not describe how many separate events each affected participant had.
What do the event counts represent?
The serious-event and other-event counts are reported separately for each listed group. The denominator accompanying a count is the number of participants at risk in that group, as recorded in the posted safety data. A count such as 2 of 4 describes the number of affected participants relative to that group's listed denominator; it is not a rate per unit of treatment time. Because treatment duration may vary among participants, event counts alone do not account for differing exposure. The registry reports a maximum treatment duration of 47 months for the primary safety observation, but group-level exposure times are not reported in the registry record.
The outcome window runs from first dose through 30 days after the last dose. This definition matters because it sets which events can contribute to the endpoint. It does not establish that an event was caused by treatment. The registry's SAE definition identifies seriousness by consequences such as death, life-threatening events, hospitalization, disability, or medical importance. Seriousness and treatment relatedness are separate classifications; treatment-relatedness results are not reported in the registry record.
Why are these summaries descriptive?
The study is recorded as non-randomized overall, open-label, and sequential. The registry explicitly warns that the arms are not a like-for-like control comparison. General statistical explanation: comparisons across non-equivalent groups can be influenced by differences in participant characteristics, disease features, prior treatment, follow-up, and exposure. Here, the expansion groups are defined by molecular tumor features and, for Group 1, prior treatment history. Therefore, contrasts among their raw counts cannot be interpreted as isolated dose effects.
No inferential results are posted for the listed outcomes. In general, a confidence interval expresses the uncertainty around an estimated quantity; it can help distinguish a relatively precise estimate from one that is compatible with a broad range of values. No confidence intervals are reported in the registry record. In general, a hypothesis test evaluates how compatible data are with a specified statistical model under a null hypothesis. No p-values or hypothesis-test results are reported in the registry record. Without those estimates and their underlying analysis details, the posted counts do not support claims of statistically significant differences.
What can sample-size planning show?
The sample-size assumptions describe an illustrative planning approach based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such a calculation is a planning illustration, not an analysis of the trial's observed power. The assumptions also specify that time-to-event calculations would use a total number of events, while other calculations would express participants per arm. No calculated planning counts are reported in the registry record, and the observed effect used for such a calculation is not reported in the registry record. These assumptions should not be mistaken for the trial's own design justification; a sample-size justification is not reported in the registry record.
General statistical explanation: a planning calculation depends on the target effect, variability or event frequency, significance threshold, allocation, and chosen power. If the target effect is uncertain, the resulting sample size is uncertain as well. Over-dispersion is a general concern when count variability exceeds what a simple statistical model expects; accounting for it can affect standard errors and uncertainty estimates. The registry does not report an over-dispersion model or any fitted model for these safety counts. No sample-size assumptions should be used to infer that the trial had adequate power for any particular safety or antitumor outcome.
How should the design affect interpretation?
Open-label means participants and study personnel were not masked to treatment according to the registry classification. General statistical explanation: awareness of treatment can affect subjective assessments and reporting, although the extent depends on the outcome and procedures. The record does not describe event-adjudication procedures or measures to reduce assessment bias. Sequential dose escalation is intended to examine doses in an ordered process, but the detailed escalation rules and decision criteria are not reported in the registry record. The registry also does not report interim-analysis plans, stopping boundaries, or the statistical plan for analyses.
The registry lists 22 outcome measures and 0 analyses. It names outcomes including response, duration of response, clinical benefit, progression-free survival, duration of stable disease, disease control, overall survival, and brimarafenib trough plasma concentration. Their numerical estimates and analysis methods are not reported in the registry record. For those outcomes, the record therefore does not support an assessment of estimate precision, handling of censoring, or model assumptions. The safety counts remain useful as descriptive observations, but they do not replace a prespecified analysis or a comparative design.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 22 outcome measures, including safety, pharmacokinetic, response, disease-control, and time-to-event outcomes. The number of posted analyses is 0. Results for these additional outcomes, including any estimates, confidence intervals, or p-values, are not reported in the registry record. A hierarchy identifying a single confirmatory outcome, or a plan for controlling false-positive findings across multiple outcomes, is not reported in the registry record.
Multiplicity is a general statistical issue that arises when many outcomes, groups, doses, or analyses are examined. Without a stated analysis hierarchy or adjustment plan, readers cannot determine whether a reported finding was designated as primary, exploratory, or selected from multiple analyses. This matters particularly for a study with several dose levels and molecularly defined expansion groups. The registry's stated primary outcome is the Phase 1a count of participants with TEAEs and SAEs; it does not provide a broader statistical plan for evaluating the secondary outcomes.
Missing-data methods are also not reported in the registry record. The posted safety counts do not describe whether any participants were excluded from the safety population, how incomplete event information was handled, or whether follow-up differed across groups. The safety population is identified for the primary endpoint, but its inclusion criteria are not reported in the registry record. Disposition by arm and reasons for missing outcome data are not reported in the registry record.
General statistical explanation: missing observations can affect interpretation when the likelihood of missingness is related to a participant's health, treatment exposure, or outcome. A clear analysis should state the population included, the handling of incomplete data, and the assumptions used. For time-to-event outcomes, censoring rules and follow-up status are also important; these details are not reported in the registry record. The absence of these details limits assessment of the listed outcomes, but it does not change the descriptive meaning of the posted participant counts. No multiplicity adjustment, missing-data sensitivity analysis, or population-specific outcome analysis is reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Phase 1a: Brimarafenib 5 mg | 2 | 4 | 50.0% |
| Phase 1a: Brimarafenib 10 mg | 8 | 12 | 66.7% |
| Phase 1a: Brimarafenib 15 mg | 5 | 7 | 71.4% |
| Phase 1a: Brimarafenib 25 mg | 3 | 7 | 42.9% |
| Phase 1a: Brimarafenib 40 mg | 5 | 8 | 62.5% |
| Phase 1a: Brimarafenib 60 mg | 4 | 4 | 100.0% |
| Phase 1b: Group 1 (Brimarafenib 25 mg) | 8 | 13 | 61.5% |
| Phase 1b: Group 1 (Brimarafenib 40 mg Randomized) | 6 | 14 | 42.9% |
| Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized) | 4 | 6 | 66.7% |
| Phase 1b: Group 2 (Brimarafenib 40 mg) | 30 | 34 | 88.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Phase 1a: Brimarafenib 5 mg | 2 of 4 |
| Phase 1a: Brimarafenib 10 mg | 5 of 12 |
| Phase 1a: Brimarafenib 15 mg | 2 of 7 |
| Phase 1a: Brimarafenib 25 mg | 2 of 7 |
| Phase 1a: Brimarafenib 40 mg | 3 of 8 |
| Phase 1a: Brimarafenib 60 mg | 2 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Phase 1a: Brimarafenib 5 mg | 4 of 4 |
| Phase 1a: Brimarafenib 10 mg | 12 of 12 |
| Phase 1a: Brimarafenib 15 mg | 7 of 7 |
| Phase 1a: Brimarafenib 25 mg | 7 of 7 |
| Phase 1a: Brimarafenib 40 mg | 8 of 8 |
| Phase 1a: Brimarafenib 60 mg | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase 1a: Brimarafenib 5 mg | Phase 1a: Brimarafenib 10 mg | Phase 1a: Brimarafenib 15 mg | Phase 1a: Brimarafenib 25 mg | Phase 1a: Brimarafenib 40 mg | Phase 1a: Brimarafenib 60 mg |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 4 | 1 of 12 | 0 of 7 | 1 of 7 | 2 of 8 | 1 of 4 |
| Pneumonia | Infections and infestations | 0 of 4 | 2 of 12 | 2 of 7 | 0 of 7 | 0 of 8 | 0 of 4 |
| Abdominal pain | Gastrointestinal disorders | 0 of 4 | 0 of 12 | 1 of 7 | 1 of 7 | 0 of 8 | 1 of 4 |
| Atrial fibrillation | Cardiac disorders | 0 of 4 | 0 of 12 | 1 of 7 | 0 of 7 | 1 of 8 | 1 of 4 |
| Small intestinal obstruction | Gastrointestinal disorders | 0 of 4 | 0 of 12 | 2 of 7 | 0 of 7 | 0 of 8 | 0 of 4 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 4 | 0 of 12 | 0 of 7 | 1 of 7 | 1 of 8 | 0 of 4 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 0 of 4 | 2 of 12 | 0 of 7 | 0 of 7 | 0 of 8 | 0 of 4 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 4 | 0 of 12 | 1 of 7 | 1 of 7 | 0 of 8 | 0 of 4 |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 4 | 1 of 12 | 0 of 7 | 1 of 7 | 0 of 8 | 0 of 4 |
| Acute kidney injury | Renal and urinary disorders | 0 of 4 | 0 of 12 | 1 of 7 | 0 of 7 | 0 of 8 | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase 1a: Brimarafenib 5 mg | Phase 1a: Brimarafenib 10 mg | Phase 1a: Brimarafenib 15 mg | Phase 1a: Brimarafenib 25 mg | Phase 1a: Brimarafenib 40 mg | Phase 1a: Brimarafenib 60 mg |
|---|---|---|---|---|---|---|---|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | 1 of 4 | 6 of 12 | 6 of 7 | 2 of 7 | 4 of 8 | 2 of 4 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 0 of 4 | 6 of 12 | 1 of 7 | 3 of 7 | 3 of 8 | 0 of 4 |
| Nausea | Gastrointestinal disorders | 0 of 4 | 3 of 12 | 5 of 7 | 1 of 7 | 3 of 8 | 0 of 4 |
| Aspartate aminotransferase increased | Investigations | 1 of 4 | 3 of 12 | 1 of 7 | 1 of 7 | 3 of 8 | 2 of 4 |
| Alanine aminotransferase increased | Investigations | 1 of 4 | 3 of 12 | 1 of 7 | 2 of 7 | 3 of 8 | 1 of 4 |
| Diarrhoea | Gastrointestinal disorders | 1 of 4 | 2 of 12 | 4 of 7 | 2 of 7 | 2 of 8 | 0 of 4 |
| Anaemia | Blood and lymphatic system disorders | 1 of 4 | 2 of 12 | 2 of 7 | 0 of 7 | 3 of 8 | 3 of 4 |
| Fatigue | General disorders | 0 of 4 | 5 of 12 | 1 of 7 | 1 of 7 | 2 of 8 | 1 of 4 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 4 | 4 of 12 | 2 of 7 | 1 of 7 | 1 of 8 | 0 of 4 |
| Pruritus | Skin and subcutaneous tissue disorders | 0 of 4 | 4 of 12 | 0 of 7 | 1 of 7 | 2 of 8 | 1 of 4 |
Serious events with the highest arm-level rate: pneumonia (33.3%), small intestinal obstruction (28.6%), abdominal pain (25.0%), intestinal obstruction (25.0%), pyrexia (25.0%).
The safety figures are participant counts within each listed treatment group. For example, the Phase 1a 5 mg group lists 2 participants with SAEs among 4 at risk, while the Phase 1a 60 mg group lists 4 among 4. The Phase 1a counts for other adverse events are 4 of 4, 12 of 12, 7 of 7, 7 of 7, 8 of 8, and 4 of 4 across the 5 mg, 10 mg, 15 mg, 25 mg, 40 mg, and 60 mg groups. These are observed counts, not evidence that dose alone accounts for differences between groups.
For Phase 1b, the SAE counts range across groups with different tumor features and treatment histories: 8 of 13, 6 of 14, 4 of 6, and 30 of 34. Other adverse-event counts are 12 of 13, 14 of 14, 6 of 6, and 34 of 34. Since group membership and study allocation are not equivalent to randomized assignment to a common control, these counts should not be treated as comparative estimates of harm.
Deaths are reported as counts for each group, but the record does not state whether they were caused by treatment or provide a cause-specific breakdown. Likewise, the listed serious-event percentages do not include event-level denominators in the posted information. Seriousness, frequency, and causal attribution are distinct concepts. The record defines SAEs by seriousness criteria; it does not establish that an SAE was treatment-related. Event timing, duration, recurrence, and participant-level overlap among event categories are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted data describe adverse events observed among participants treated with brimarafenib in the listed Phase 1a and Phase 1b groups. They give group-specific counts of participants with SAEs and other adverse events, as well as death counts. They also identify several serious-event terms with percentages. The counts are useful for describing what was recorded in these groups during the specified safety observation period.
They do not determine whether brimarafenib caused an event. The registry's SAE definition concerns the seriousness of an event, not its relationship to treatment. Treatment-relatedness assessments, event-level detail, and reasons for death are not reported in the registry record. The counts also do not establish comparative risk because the record does not present a like-for-like control treatment group. The overall allocation is marked non-randomized, even though some Phase 1b arm descriptions use randomized wording; the relationship between those descriptions is not explained in the registry record.
The results do not establish an antitumor effect. The study aimed to evaluate preliminary antitumor activity, and the registry lists outcomes such as response, disease control, progression-free survival, and overall survival. Numerical analyses for these outcomes are not reported in the registry record. There are no posted confidence intervals or hypothesis-test results, and the record lists 0 analyses. Therefore, the posted safety counts cannot be used to infer efficacy, statistical significance, or the precision of an efficacy estimate.
Nor do the counts establish that the different doses have different safety profiles. The groups are small and are not a like-for-like dose comparison; Phase 1b groups differ by molecular tumor features and prior treatment criteria. General statistical explanation: raw counts can be informative for describing observed events, while causal or comparative conclusions require a design and analysis that address differences between groups and uncertainty. The sample-size assumptions are planning illustrations, not observed power or evidence that a target effect was detectable. Overall, the record supports a descriptive account of the listed safety observations, with substantial limits on comparative and outcome interpretation.
13. Why This Trial Matters Statistically
This study is statistically notable as an early-phase, first-in-human evaluation with dose escalation and expansion across molecularly defined tumor groups. The design brings together different questions: safety and tolerability across ascending dose groups, pharmacokinetic characterization, and preliminary activity in selected tumor subsets. Those questions do not all have the same statistical structure. Participant event counts describe safety, trough concentration is a pharmacokinetic measure, and response or survival outcomes require their own definitions and analysis methods.
The registry's non-randomized overall allocation and lack of a like-for-like control comparison are central to reading the posted counts. A dose-escalation series can document events in the participants who received each dose, but differences in raw counts do not isolate a dose effect when the groups are small and may differ in composition or exposure. The expansion groups add further heterogeneity through molecular eligibility and prior-treatment criteria. This makes careful separation of descriptive safety reporting from comparative inference especially important.
The record also illustrates why the presence of many listed outcomes is not the same as having interpretable analyses for all of them. It lists 22 outcome measures but 0 analyses. Without outcome estimates, uncertainty intervals, and analysis details, the registry record cannot support conclusions about antitumor activity or the precision of those estimates. In general, transparent statistical reporting helps readers distinguish exploratory observations from confirmatory evidence and understand how multiple outcomes and missing data were addressed. Those details are not reported in the registry record.
For clinical researchers and biostatisticians, the key lesson is methodological rather than a claim about treatment: early-phase evidence should be read in the context of the actual design, population definitions, endpoint window, and level of analysis. The posted safety counts provide descriptive information, while the absent comparative and outcome analyses limit the scope of statistical conclusions that can be drawn.
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 registry status is terminated, but the reason for termination is not reported in the registry record. Enrollment is listed as 109 overall; the record does not explain how enrollment was distributed across groups or how many participants contributed to each outcome analysis beyond the safety denominators shown. The relation between overall non-randomized allocation and Phase 1b arm descriptions that use randomized wording is not explained.
Safety results are presented as participant counts. Event-level data, severity grades apart from SAE status, timing, duration, recurrence, exposure-adjusted rates, and treatment-relatedness assessments are not reported in the registry record. The listed death counts do not include causes or attribution. The serious-event terms are accompanied by percentages, but corresponding event-level counts and denominators are not reported in the posted information.
The record identifies a safety population but does not report its precise criteria or participant disposition by group. Missing-data rules, handling of incomplete follow-up, and sensitivity analyses are not reported in the registry record. The registry lists secondary outcomes for response, disease control, survival, and pharmacokinetics, but their numerical analyses and methods are not reported. No confidence intervals, p-values, or adjusted estimates are posted, and the number of analyses is 0.
The study is open-label, and the record does not describe event adjudication or other procedures to limit assessment bias. Dose-escalation rules, dose-selection criteria, interim analyses, and the statistical plan are not reported in the registry record. These omissions constrain interpretation of both the safety counts and the broader study objectives. The posted data should not be treated as a controlled comparison, a causal attribution of events, or a complete evaluation of the trial's antitumor outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors — NCT04249843.
- Registry record last updated 2026-08-31; status last verified 2026-04.
- Results first posted 2026-08-31.
- 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
NCT04249843 is a Phase 1a/1b, open-label study of brimarafenib in participants with advanced or refractory tumors. The registry records overall non-randomized allocation, sequential modeling, enrollment of 109, and terminated status. Phase 1a evaluated dose levels from 5 mg through 60 mg; Phase 1b included expansion groups defined by BRAF tumor features and prior treatment.
The primary outcome is the Phase 1a number of participants with TEAEs and SAEs, measured from first dose through 30 days after the last dose. The posted safety results include participant counts for Phase 1a and Phase 1b groups, as well as death counts and selected serious-event terms. The record lists 22 outcome measures and 0 analyses. Numerical analyses for the listed antitumor, survival, and pharmacokinetic outcomes are not reported in the registry record. The posted counts are descriptive and do not provide a like-for-like control comparison or establish treatment causation.