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 Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) (NCT03224819), a non-randomized early/phase 1 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03224819 |
| Phase | EARLY/Phase 1 |
| Condition | Acute Myeloid Leukemia |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 46 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Amgen |
| Results posted | Yes |
2. Clinical Question
Population
Adults with relapsed/refractory acute myeloid leukemia (AML) were eligible for this first-in-human study. The primary endpoint population is described as all enrolled participants who received at least 1 dose of study drug. The registry record lists 46 enrolled participants overall, but the posted safety groups do not include every participant in every cohort; group-specific numbers at risk are shown for the reported safety outcomes.
Intervention
The study evaluated emerfetamab, also identified as AMG 673, administered as short-term intravenous infusions. Dose escalation used Schedule A and Schedule B. Schedule A is described as Day 1/Day 5 dosing in 14-day cycles. Schedule B used once-daily dosing for cycle 1, followed by twice-weekly dosing in following cycles. The study also allowed expansion enrollment at a dose at or below the maximum tolerated dose estimated in dose escalation.
Comparator
There was no randomized control group. The study was non-randomized, unmasked, and sequential, with participants enrolled into dose cohorts and schedules. Comparisons between cohorts therefore do not have the protection of random allocation, and the groups should not be interpreted as like-for-like treatment arms. The registry record does not report a separate comparator intervention.
Primary question
The primary objectives were to evaluate emerfetamab’s safety and tolerability and to estimate the maximum tolerated dose and/or a biologically active dose, such as a recommended phase 2 dose. The registered primary endpoint counts participants with treatment-emergent adverse events. The registry record describes adverse-event grading and the observation period, but does not report an overall primary-endpoint count or a dose-estimation result. The evidence posted therefore supports a description of the reported safety counts, not a comparative efficacy conclusion.
3. Trial Design
This was an early-phase, first-in-human study of emerfetamab in adults with relapsed/refractory AML. The registry classifies it as phase 1, non-randomized, unmasked, and sequential. It records 46 participants enrolled. The study began on 2017-09-07, had a primary completion date of 2020-12-28, and is listed as terminated. The reason for termination is not reported in the registry record.
Dose escalation was organized around two administration schedules. Schedule A used Day 1/Day 5 dosing in 14-day cycles. Schedule B used once-daily dosing for cycle 1, then twice-weekly dosing in following cycles. The safety records list cohorts for Schedule A, including dose levels from 0.05 µg through 110 µg and a 36/72 µg cohort, as well as Schedule B cohorts at 72 µg and 110 µg. The registry describes possible expansion enrollment for each schedule at a dose at or below the maximum tolerated dose estimated during escalation. The full starting-dose description is not reported in the registry record.
The sequential dose-escalation design is intended to gather safety information across dose cohorts while estimating a dose for further study. Because treatment allocation was not randomized and no control arm is listed, cohort differences can reflect differences in participants, schedules, exposure, or other factors as well as dose. The study’s primary emphasis was safety, tolerability, and dose estimation; the registry also lists pharmacokinetic outcomes. It does not report a protocol-level statistical analysis plan, dose-escalation decision rules, or a final selected dose.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Only the first 6 of 14 groups are shown.
Overall Study
| Stage | Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A Cohort 6: 7 µg Emerfetamab |
|---|---|---|---|---|---|---|
| STARTED | 1 | 1 | 3 | 3 | 3 | 3 |
| COMPLETED | 1 | 0 | 3 | 2 | 2 | 1 |
| NOT COMPLETED | 0 | 1 | 0 | 1 | 1 | 2 |
Reasons for not completing this period:
| Reason | Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A Cohort 6: 7 µg Emerfetamab |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 |
| Sponsor Decision | 0 | 0 | 0 | 1 | 1 | 2 |
| Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 |
| Death | 0 | 1 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least 1 dose of study drug.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Only the first 6 of 15 groups are shown.
| Characteristic | Unit | Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A Cohort 6: 7 µg Emerfetamab |
|---|---|---|---|---|---|---|---|
| Participants analysed | 1 | 1 | 3 | 3 | 3 | 3 | |
| Age, Continuous | years | 25.0 | 61.0 | 49.3 (SD 16.3) | 69.3 (SD 8.1) | 60.3 (SD 23.9) | 60.7 (SD 18.9) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 2 | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 0 | 1 | 1 | 2 | 2 | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 1 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 | 0 | 3 | 3 | 3 | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 0 | 0 | 0 | 2 | 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 | 1 | 1 | 3 | 3 | 1 | 3 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events, measured over From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with treatment-emergent adverse events. The observation window runs from the first dose of study drug until the end of study. The registered population consists of enrolled participants who received at least 1 dose. The registry reports a median observation duration of 1.22 months, with a minimum of 0.10 and a maximum of 5.98 months.
Adverse events were graded using Common Terminology Criteria for Adverse Events, version 4.0. The record defines grades from mild through death due to an adverse event. It also defines serious adverse events by criteria such as fatality, life threat, hospitalization, persistent or significant disability, congenital anomaly, or another medically important serious event.
Counting participants with events is a direct way to describe the observed safety experience in an early-phase study. It can show whether adverse events were reported among exposed participants and supports review of event severity and seriousness. A participant count alone does not describe how often an event recurred, how long it lasted, or whether it was caused by study treatment. The registry record does not report an overall result for this primary endpoint, so its total cannot be inferred from the cohort-level serious and other adverse-event counts.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies safety and tolerability as the study’s primary focus. Its posted safety information is organized by dose cohort and schedule, with counts at risk, counts affected by serious adverse events, counts affected by other adverse events, and a deaths column. These are descriptive data from a non-randomized dose-escalation study, not results from a controlled comparison.
The cohort sizes shown are small. For example, Schedule A Cohort 1 lists 1 participant at risk for serious adverse events and 1 affected; Schedule A Cohort 8 lists 3 at risk and 3 affected. Schedule B Cohort 1 lists 5 at risk and 1 affected by serious adverse events. These counts describe what was recorded in those cohorts, but they do not establish that a dose caused an event or that one cohort had a safer experience than another. Differences in cohort counts can arise from differences in group size, schedule, follow-up, and the participants enrolled.
For other adverse events, the registry lists 1 affected participant among 1 at risk in Schedule A Cohort 1, and 6 affected among 6 at risk in Schedule A Cohort 9. Such counts indicate that the event category was recorded for the participants counted as at risk in those groups. They do not convey the range of event types or grades within the broader category. The primary endpoint’s overall participant count is not reported in the registry record.
The registry lists deaths in some cohorts, including 1 in Schedule A Cohort 2, 1 in Schedule A Cohort 8, and 1 in Schedule A Cohort 12; the other displayed cohorts list 0. These entries should not be treated as proof that deaths were caused by emerfetamab. The causal relationship of these deaths to treatment is not reported in the registry record. Likewise, counts for serious adverse events and other adverse events do not by themselves indicate attribution, preventability, or clinical importance beyond the definitions recorded.
No efficacy result or between-group treatment effect is reported in the registry record. This is not a randomized comparison, and no comparator arm is listed. Therefore, the posted information supports a limited account of observed safety counts and study structure. It does not support a causal comparison between dose levels, a precise estimate of population risk, or a conclusion about treatment benefit.
9. Statistical Methods Explained
What does a participant count describe?
The primary endpoint is a count of participants who experienced treatment-emergent adverse events during the stated observation period. A participant count differs from a count of event episodes: the endpoint concerns people with an event, not how many times each event occurred. The registry also presents serious and other adverse-event counts by cohort. Those are useful for describing recorded events in the enrolled groups, but they do not replace a complete event-level account of type, severity, duration, and attribution.
Why does the design matter?
General statistical principle: random allocation helps balance measured and unmeasured participant characteristics across treatment groups, making treatment contrasts easier to interpret causally. This study was non-randomized and sequential, so cohort membership was linked to dose escalation and schedule rather than random assignment. Comparisons across cohorts can consequently be affected by their different participants, follow-up, and treatment schedules. The sequential structure is relevant to safety and dose estimation, but it does not create a randomized estimate of treatment effect.
How should uncertainty be understood?
General statistical principle: a confidence interval describes a range of values compatible with the observed data under a statistical model. With small cohort counts, estimates of event frequency can be imprecise; an observed count should not be read as a precise estimate of what would occur in a broader population. The registry record does not report confidence intervals for the primary safety endpoint. It also does not report a model-based comparison of the adverse-event counts, so no such comparison should be inferred from the posted data.
General statistical principle: over-dispersion matters when observed variability is greater than a model assumes. A model that does not accommodate that extra variability can understate uncertainty. The record does not report an over-dispersion assessment or a statistical model for the primary endpoint. As a result, there is no basis in the registry record to evaluate whether a particular variance assumption was considered or whether adjusted uncertainty estimates were used.
What do the planning illustrations represent?
The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are based on a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used those assumptions. The record does not report that this study randomized participants equally between two arms, and the study is explicitly non-randomized. Any such illustration should therefore be understood as a hypothetical planning exercise, not as a description of the trial’s actual design or an observed power calculation.
For time-to-event planning, the stated convention is a total number of events using the Schoenfeld approach; other planning results are expressed as participants per arm. These distinctions matter because event targets and per-arm participant counts are different quantities. The registry record does not report the trial’s own sample-size justification or a power calculation. Sample-size planning illustrations are not observed power and do not establish the probability that the study detected an effect.
What can be said about the dose estimate?
The stated objectives include estimating the maximum tolerated dose and/or a biologically active dose, such as a recommended phase 2 dose. The registry record does not report the dose-escalation decision rules, a final maximum tolerated dose, or a recommended phase 2 dose. The cohort counts alone cannot reconstruct a dose-finding algorithm or establish which dose was selected. Such conclusions require the protocol and the investigators’ analysis, neither of which is reported in the registry record.
The record lists 20 outcome measures, including pharmacokinetic measures such as maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. It does not report analysis records for these outcomes. Listing a measure indicates that it was designated for assessment; it does not establish that a result was posted or that the measure was included in a particular inferential analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures, with safety and tolerability central to the primary objectives and pharmacokinetic measures among the secondary outcomes. When multiple outcomes or analyses are examined, the chance of at least one apparently notable result can increase. General statistical principle: multiplicity procedures can control that risk, but the appropriate approach depends on the prespecified questions and analysis plan. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a plan for handling repeated analyses.
The registry lists no analysis records. It does not report a statistical analysis plan for the posted safety endpoint, including whether any group comparisons or adjusted estimates were planned. A lack of posted analysis details should not be interpreted as evidence that no analysis was conducted; it means that the analysis approach is not reported in the registry record.
The primary endpoint population is described as all enrolled participants who received at least 1 dose of study drug. That definition identifies an exposed population for the safety assessment. The registry record does not report participant-level exclusions, missing outcome handling, or whether the analysis population for other outcomes differed. Missing-data methods and the extent of missing outcome data are not reported in the registry record.
These omissions limit assessment of how the investigators handled multiple outcomes, incomplete follow-up, and any differences between enrolled and analyzed participants. The median duration and range of observation are reported, but those summaries do not show whether every participant had the same opportunity for adverse events to be observed. Consequently, the cohort counts are best read as descriptive posted results rather than as adjusted estimates with a documented inferential framework.
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 |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | 1 | 1 | 100.0% |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | 1 | 1 | 100.0% |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | 2 | 3 | 66.7% |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | 1 | 3 | 33.3% |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | 2 | 3 | 66.7% |
| Schedule A Cohort 6: 7 µg Emerfetamab | 1 | 3 | 33.3% |
| Schedule A Cohort 7: 9 µg Emerfetamab | 2 | 3 | 66.7% |
| Schedule A Cohort 8: 18 µg Emerfetamab | 3 | 3 | 100.0% |
| Schedule A Cohort 9: 36 µg Emerfetamab | 2 | 4 | 50.0% |
| Schedule A Cohort 10: 72 µg Emerfetamab | 5 | 6 | 83.3% |
| Schedule A Cohort 11: 110 µg Emerfetamab | 3 | 4 | 75.0% |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | 4 | 4 | 100.0% |
| Schedule B Cohort 1: 72 µg Emerfetamab | 1 | 5 | 20.0% |
| Schedule B Cohort 2: 110 µg Emerfetamab | 2 | 3 | 66.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | 0 of 1 |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | 1 of 1 |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | 0 of 3 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | 0 of 3 |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | 0 of 3 |
| Schedule A Cohort 6: 7 µg Emerfetamab | 0 of 3 |
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 |
|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | 1 of 1 |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | 1 of 1 |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | 2 of 3 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | 3 of 3 |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | 3 of 3 |
| Schedule A Cohort 6: 7 µg Emerfetamab | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A Cohort 6: 7 µg Emerfetamab |
|---|---|---|---|---|---|---|---|
| Sepsis | Infections and infestations | 1 of 1 | 1 of 1 | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 3 |
| Cytokine release syndrome | Immune system disorders | 0 of 1 | 0 of 1 | 0 of 3 | 1 of 3 | 0 of 3 | 1 of 3 |
| Pneumonia | Infections and infestations | 0 of 1 | 1 of 1 | 1 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Platelet count decreased | Investigations | 0 of 1 | 1 of 1 | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 3 |
| White blood cell count decreased | Investigations | 1 of 1 | 1 of 1 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Abdominal pain | Gastrointestinal disorders | 0 of 1 | 1 of 1 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Perirectal abscess | Infections and infestations | 1 of 1 | 0 of 1 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Pneumonia fungal | Infections and infestations | 0 of 1 | 0 of 1 | 1 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 0 of 1 | 1 of 1 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 1 | 1 of 1 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A Cohort 6: 7 µg Emerfetamab |
|---|---|---|---|---|---|---|---|
| Decreased appetite | Metabolism and nutrition disorders | 1 of 1 | 0 of 1 | 1 of 3 | 0 of 3 | 2 of 3 | 1 of 3 |
| Diarrhoea | Gastrointestinal disorders | 1 of 1 | 1 of 1 | 1 of 3 | 0 of 3 | 1 of 3 | 0 of 3 |
| Nausea | Gastrointestinal disorders | 1 of 1 | 0 of 1 | 1 of 3 | 1 of 3 | 0 of 3 | 1 of 3 |
| Chills | General disorders | 0 of 1 | 0 of 1 | 0 of 3 | 1 of 3 | 2 of 3 | 1 of 3 |
| Hypervolaemia | Metabolism and nutrition disorders | 1 of 1 | 1 of 1 | 0 of 3 | 1 of 3 | 0 of 3 | 1 of 3 |
| Lethargy | Nervous system disorders | 1 of 1 | 0 of 1 | 2 of 3 | 0 of 3 | 0 of 3 | 1 of 3 |
| Rash | Skin and subcutaneous tissue disorders | 1 of 1 | 0 of 1 | 0 of 3 | 2 of 3 | 1 of 3 | 0 of 3 |
| Pyrexia | General disorders | 0 of 1 | 0 of 1 | 1 of 3 | 1 of 3 | 0 of 3 | 1 of 3 |
| Infusion related reaction | Injury, poisoning and procedural complications | 0 of 1 | 0 of 1 | 0 of 3 | 1 of 3 | 2 of 3 | 0 of 3 |
| Procedural pain | Injury, poisoning and procedural complications | 1 of 1 | 0 of 1 | 1 of 3 | 0 of 3 | 0 of 3 | 1 of 3 |
Serious events with the highest arm-level rate: abdominal pain (100.0%), perirectal abscess (100.0%), pneumonia (100.0%), sepsis (100.0%), platelet count decreased (100.0%).
The safety records give, for each listed cohort, the number at risk and the number affected by serious adverse events, the number at risk and affected by other adverse events, and a death count. For example, Schedule A Cohort 7 lists 3 at risk and 2 affected for serious events, and 3 at risk and 3 affected for other events. Schedule B Cohort 2 lists 3 at risk and 2 affected by serious events, and 3 at risk and 3 affected by other events. These are cohort-level counts, not randomized comparisons.
The registry’s list of top serious adverse-event terms displays Abdominal pain, Perirectal abscess, Pneumonia, Sepsis, Platelet count decreased, and White blood cell count decreased, each with 100.0%. The denominator used for these displayed percentages is not reported in the registry record, so the percentages should not be interpreted as the proportion of all enrolled participants with each term.
Seriousness is defined by the registry using criteria that include fatality, life threat, hospitalization, persistent or significant disability, congenital anomaly, or another medically important event. A serious event is not necessarily a treatment-related event. The death counts likewise do not establish treatment causality; attribution is not reported in the registry record. The posted information does not provide the overall count for the primary endpoint or a complete account of each event’s severity and relationship to study drug.
12. What the Result Does, and Does Not, Mean
The study addresses an important early-phase statistical task: describing safety while escalating doses and considering which dose or schedule merits further evaluation. The registry records two administration schedules, multiple dose cohorts, and adverse-event counts. These features allow readers to understand the broad structure of the safety assessment and the kinds of events listed in the record.
The posted counts do not establish that emerfetamab caused any particular event, nor do they show that a dose or schedule is safer than another. This study was non-randomized and has no listed control group. Cohorts are small, differ in size, and were enrolled sequentially. A numerical contrast between them would not isolate a dose effect from those design features and other possible differences in participants or observation.
The record also does not report an overall primary-endpoint result, an efficacy result, a final dose-selection result, or a statistical analysis plan. The posted safety information therefore cannot establish a treatment benefit, estimate a controlled treatment effect, or confirm a dose for later-phase testing. The study’s stated objectives should not be confused with results: an objective to estimate a maximum tolerated or biologically active dose does not mean that such an estimate is posted.
General statistical principle: interpretation should account for both the size of an estimate and its precision. Here, the reported cohort counts are descriptive, and confidence intervals or other precision estimates for the primary safety outcome are not reported in the registry record. The best-supported reading is therefore narrow: the registry documents adverse-event counts among participants in listed cohorts, alongside the study’s design and objectives. It does not provide enough information for a causal or broadly generalizable conclusion about treatment effects.
13. Why This Trial Matters Statistically
Early-phase dose-escalation studies pose statistical challenges that differ from those in randomized efficacy trials. Their purpose includes characterizing tolerability across doses and schedules and informing later study choices. Sequential enrollment makes the accumulating safety experience relevant to the next dose decisions, while the small cohort sizes mean that event counts can be difficult to interpret as population risks.
This study illustrates why design labels matter. It is non-randomized, unmasked, and sequential, rather than a comparison in which participants were randomly assigned to treatment groups. That structure can be appropriate to early dose exploration, but it limits the interpretation of differences between cohorts. A higher or lower count in one cohort cannot, on its own, establish a dose-related change in risk.
It also matters to distinguish a study objective from a posted result. The primary objectives include safety, tolerability, and dose estimation. The registry record lists cohort-level safety counts and the duration of observation, but does not report a total primary-endpoint count, a final dose estimate, or the statistical plan. Clear separation of those elements helps prevent readers from treating descriptive counts as a definitive dose-finding result.
Finally, the planning assumptions attached to sample-size illustrations should not be mistaken for the study’s design. Hypothetical equal allocation and effect-based planning do not turn this non-randomized study into a comparative trial, and planning calculations are not observed power. Keeping design, analysis, and interpretation distinct is essential when assessing what a small early-phase study can and cannot establish.
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 principal limitation is the absence of a randomized comparator. The study’s sequential, non-randomized design does not support a like-for-like comparison of dose cohorts, and no control arm is listed. The unmasked design is also relevant when interpreting adverse-event reporting, because knowledge of treatment assignment may influence how events are observed or recorded; the registry record does not describe procedures intended to address that possibility.
The safety cohorts are small and vary in size. The reported counts do not include confidence intervals for the primary endpoint, and the overall primary-endpoint result is not reported in the registry record. The posted duration summary does not show individual follow-up or the completeness of adverse-event reporting. Missing-data handling, participant-level exclusions, and the analysis population for outcomes other than the primary safety endpoint are not reported in the registry record.
The registry does not report the reason the study was terminated, the dose-escalation decision rules, a final selected dose, or a statistical analysis plan. It lists 20 outcome measures but no analysis records. This limits assessment of outcome prioritization, multiplicity, and how any analyses were conducted. The listed serious-event terms and percentages also lack a reported denominator basis, restricting their interpretation.
Finally, the posted information does not provide efficacy results or establish causality for serious adverse events or deaths. The study’s first-in-human, early-phase setting and limited cohort data mean that its registry record is primarily descriptive. These limitations apply to interpretation of this record and do not, by themselves, determine what may be available in other sources.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) — NCT03224819.
- Registry record last updated 2023-09-01; status last verified 2022-10.
- Results first posted 2023-09-01.
- 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
NCT03224819 is a phase 1, first-in-human study of emerfetamab in adults with relapsed/refractory AML. The registry records 46 participants enrolled, a non-randomized, unmasked, sequential design, and a terminated status. The study began on 2017-09-07, with primary completion on 2020-12-28.
The primary objectives were safety, tolerability, and estimation of a maximum tolerated and/or biologically active dose. The primary endpoint counts participants with treatment-emergent adverse events from first dose until the end of study. The registry describes two dosing schedules and posts safety counts by cohort, but does not report the overall primary-endpoint result, the reason for termination, a final dose estimate, or the statistical analysis plan.
The safety counts are descriptive and do not support causal comparisons between cohorts. Efficacy results and treatment attribution for deaths are not reported in the registry record.