Study of AMG 256 in Adult Subjects With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of AMG 256 in Adult Subjects With Advanced Solid Tumors (NCT04362748), a non-randomized phase 1 study. The primary outcome is Number of Participants Who Experienced Dose Limiting Toxicities (DLTs).

2. Clinical Question

The study asked whether AMG 256 could be administered to adults with advanced solid tumors while characterizing early toxicity and determining a maximum tolerated dose or recommended phase 2 dose. Its primary endpoint counted participants with dose-limiting toxicities during the defined early treatment period. The study also listed pharmacokinetic outcomes and measures of tumor response as secondary outcomes.

The question is characteristic of early dose evaluation: the focus is on defining and describing toxicity during treatment, rather than estimating a comparative treatment effect against a control group. The study also listed objective response rate under modified RECIST v1.1 and immune objective response rate under modified iRECIST, alongside pharmacokinetic measures. Those outcomes broaden the questions the study was set up to assess, but their results are not reported in the registry information available for this account.

3. Trial Design

The registry identifies NCT04362748 as a Phase 1 study of AMG 256 in adult subjects with advanced solid tumors. The study was non-randomized, unmasked and sequential. It lists enrollment of 34 and a completed status, with a start date of 2020-09-15 and a primary completion date of 2023-09-21.

The design had a dose escalation phase and dose expansion phases. In dose escalation, the stated purpose was to determine the maximum tolerated dose or recommended phase 2 dose of AMG 256. The two dose expansion groups were described as receiving the dose identified during dose escalation. The registry does not report the dose levels administered, the escalation rules, or how the decision to proceed to expansion was made.

Because allocation was non-randomized and no masking was used, the cohort descriptions do not constitute randomized treatment comparisons. The cohorts are part of a sequential dose evaluation, not parallel arms assigned by chance to intervention and control. Any differences between cohorts could reflect their place in the study’s dose evaluation or other cohort characteristics; the registry information does not support attributing such differences to a treatment comparison.

The primary outcome was the number of participants with dose-limiting toxicities from Day 1 to Day 28. The primary population was defined as the DLT Evaluable Set: enrolled participants who received at least one dose and had an evaluable endpoint. A count for that endpoint and the size of that evaluable population are not reported in the registry record. The registry also lists pharmacokinetic, objective response and immune response outcomes, but no outcome analyses are listed.

The registry does not report the detailed protocol for dose escalation, the planned statistical analysis, or sample-size justification. The study’s listed enrollment should not be treated as the number of participants evaluable for every outcome, since the endpoint populations may differ and the record does not give all such population counts.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: This trial was planned to be conducted in two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). Part 1 enrolled participants into 11 dose escalation cohorts. Participants in cohorts 1 to 9 received AMG 256 as intravenous (IV) infusion every week (QW) at dose ranging from 0.6 mg to 1400 mg. Subsequently, participants in cohorts 1a and 2a received AMG 256 every 2 weeks (Q2W) at doses 1000 mg and 2000 mg respectively. Part 2 was not conducted.

Only the first 6 of 11 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT Evaluable Set: all participants that were enrolled and received at least 1 dose of AMG 256 with an evaluable DLT endpoint.

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 Analysis Set consisted of all participants that were enrolled and received at least 1 dose of AMG 256.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced Dose Limiting Toxicities (DLTs), measured over Day 1 to Day 28.

The primary endpoint counts participants who experienced a dose-limiting toxicity, or DLT, from Day 1 to Day 28. The registry defines the DLT Evaluable Set as participants who enrolled, received at least one dose of AMG 256 and had an evaluable DLT endpoint. The registry record does not report the number of participants with a DLT or the number included in this endpoint population.

The endpoint applies specified Common Terminology Criteria for Adverse Events grades and clinical circumstances during the first 28 days after the first administration. Listed DLT categories include treatment-related grade 5 toxicity; grade 4 neutropenia or thrombocytopenia; febrile neutropenia; grade 4 anemia; and certain grade 3 or 4 non-hematologic toxicities. The definition also includes recurrent grade 2 pneumonitis, a specified delay in cycle 2 treatment due to trial-drug-related toxicity in dose escalation, and toxicity requiring permanent discontinuation of AMG 256. Exceptions to some toxicity categories are described in the registry definition.

General: In dose evaluation, a DLT endpoint is used to describe whether treatment-related toxicity reaches prespecified severity criteria during a defined observation window. Such an endpoint can inform dose selection. It does not by itself establish longer-term safety, comparative benefit, or whether a treatment improves tumor outcomes. Those conclusions require other evidence and, for this study, the relevant outcome results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation is constrained by the structure and level of detail in the registry record. The study is described as Phase 1, non-randomized, unmasked and sequential. Its stated primary outcome is a participant count, and the registry lists no analyses. The statistical plan, including any planned summaries or inferential procedures, is not reported in the registry record.

What a participant count conveys

The primary outcome is the number of participants with at least one qualifying DLT during the specified period. A count describes how many participants met the endpoint definition in the endpoint population. To interpret the frequency of DLTs, readers would also need the size of that population. The registry definition identifies the DLT Evaluable Set, but its size and the number with DLTs are not reported. A count alone would not describe the range of uncertainty around an event frequency; an interval estimate could help express that uncertainty, but none is reported for this endpoint in the registry information.

The outcome is based on toxicity criteria, not on an undifferentiated count of every adverse event. The definition specifies severity grades and clinical circumstances, along with exceptions. Consistent application of those criteria is important: events that do not meet the endpoint definition are not DLTs merely because they are adverse events. The registry describes the endpoint rules, but it does not report the individual adjudication process or the resulting participant-level classifications.

Why the sequential design matters

In a sequential dose-evaluation study, later groups are studied in the context of information gathered earlier. The registry says dose escalation was intended to determine the maximum tolerated dose or recommended phase 2 dose, and that expansion groups would receive the dose identified during escalation. It does not report the specific escalation algorithm, decision thresholds, dose levels, or rules for moving between phases. Those details should not be inferred from the broad design label.

Since participants were not randomly allocated and there was no masking, cohorts are not randomized control groups. Descriptive comparisons across cohorts can show how reported outcomes varied, but cannot isolate a treatment effect in the way a suitable randomized comparison is designed to do. Differences may arise from dose or cohort characteristics, and the registry information does not provide an analysis that adjusts for such factors.

What statistical precision would mean

General: A confidence interval is a range of values compatible with an estimate under a specified statistical model. It conveys uncertainty that a single count or proportion does not show. For a small group, the interval can be wide, reflecting limited information. The relevant denominator and an estimate are necessary to interpret such an interval. Neither the primary DLT count nor its evaluable population size is reported in the registry record, and no interval is listed for that endpoint.

General: A p-value addresses compatibility between observed data and a specified null model, given the assumptions of the test. It is not a measure of clinical importance, and it does not replace an effect estimate or its uncertainty. The registry lists no outcome analyses, and no p-value for the primary endpoint is reported. No hypothesis-testing procedure should be attributed to the study from the information.

Reading the planning illustrations

Planning sample sizes are different from observed study results. The described planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect to detect set as a stated fraction of an observed effect. The illustrations are not the trial’s own design justification, and their values should not be read as observed power. The registry record does not report the trial’s sample-size justification.

The study itself is non-randomized, and the record explicitly cautions that its arms are not a like-for-like control comparison. Therefore, a planning calculation framed around two equally allocated arms should not be mistaken for evidence that this study conducted such a comparison. A planning estimate is conditional on its assumptions and does not demonstrate that a study had a particular probability of detecting an effect after the results are observed.

Multiple outcomes and analysis choices

The registry lists 16 outcome measures, including the primary toxicity endpoint, pharmacokinetic measures, and response outcomes. Multiple outcomes can raise questions about how results should be interpreted across endpoints, particularly if formal hypothesis tests are conducted. The registry record does not report a multiplicity strategy or outcome analysis entries. It is therefore not possible to state whether adjustments were planned or performed.

The record also does not report methods for missing data, endpoint censoring, or sensitivity analyses. The primary population definition indicates that an evaluable endpoint is required, but does not explain how participants without an evaluable endpoint were handled. General statistical principles can clarify what such methods are intended to address, but they cannot fill in an unreported study procedure.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1", "Cohort 2", "Cohort 3", "Cohort 4", "Cohort 5", "Cohort 6")
n      <- c(1, 1, 1, 2, 3, 3)
events <- c(0, 0, 0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Cohort 2  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Cohort 3  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Cohort 4  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Cohort 5  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 6  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures, spanning the primary DLT count, pharmacokinetic measures, objective response rate under modified RECIST v1.1, and immune objective response rate under modified iRECIST. The record lists no analyses. It does not report which outcomes were formally tested, a testing hierarchy, or a method for addressing multiplicity. Without those details and without reported outcome results, no conclusion about multiplicity adjustment can be made.

General: When multiple outcomes are tested, the chance of at least one apparently unusual result can increase if each test is treated independently at its own threshold. A prespecified hierarchy or adjustment can help control that issue. Whether a correction is relevant depends on the analysis plan and the role of each outcome. The registry record does not report such a plan, so no particular method should be assumed.

The DLT Evaluable Set is defined as enrolled participants who received at least one dose and had an evaluable DLT endpoint. The record does not report its size or the number of participants excluded from it. It also does not explain how missing or unevaluable endpoint information was handled, whether participants were analyzed according to any other population definition, or whether sensitivity analyses were performed. These details are not reported in the registry record.

General: Missing outcome data can affect estimates if the participants without recorded outcomes differ systematically from those with observed outcomes. Transparent reporting of the analysis population and missing-data approach helps readers judge that risk. Here, the population definition is available, but the actual population count and missing-data procedures are not. The listed enrollment of 34 should not be assumed to be the denominator for every outcome.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (100.0%), eyelid ptosis (50.0%), multiple organ dysfunction syndrome (50.0%), abdominal sepsis (50.0%), escherichia sepsis (33.3%).

The registry reports serious adverse event and other adverse event counts separately by cohort, alongside participants at risk and deaths. For example, Cohort 1 lists 0 serious adverse events among 1 participant at risk and 1 participant with other adverse events among 1 at risk. Cohort 1a lists 4 participants affected by serious adverse events among 7 at risk, and 7 affected by other adverse events among 7 at risk. Cohort 8 lists 1 participant affected by serious adverse events among 4 at risk and 3 affected by other adverse events among 4 at risk. These are cohort-specific descriptive counts, not randomized comparisons.

The deaths column is also reported by cohort. For example, Cohort 4 lists 1 death, Cohort 6 lists 2 deaths, and Cohort 1 lists 0 deaths. The entries should not be combined across cohorts to create an overall figure unless a valid population and aggregation rule are specified; those are not reported in the registry information.

The listed serious adverse event terms include Pyrexia at 100.0%, Eyelid ptosis at 50.0%, Multiple organ dysfunction syndrome at 50.0%, and Abdominal sepsis at 50.0%. The record does not report the denominators for these term-specific percentages or how terms map to individual cohorts. Such entries describe reported events; they do not establish cause or comparative risk. The small cohort counts also mean that each participant can materially affect a cohort’s descriptive tally.

13. What the Result Does, and Does Not, Mean

The record establishes that this was a completed Phase 1, non-randomized, unmasked, sequential study of AMG 256 in adults with advanced solid tumors. Its primary purpose was to evaluate safety and tolerability and to determine a maximum tolerated dose or recommended phase 2 dose. The primary endpoint definition and its observation period are reported, but the endpoint result and the dose decision are not.

The listed enrollment of 34 is a study-level entry, not a reported DLT count or a denominator for every outcome. The primary population is defined by receipt of at least one dose and an evaluable DLT endpoint, but the number meeting that definition is not reported. The study’s secondary outcomes include pharmacokinetic measures and tumor-response measures, but their results are also not reported in the registry record.

The cohort-level adverse event entries provide descriptive safety information, including counts of participants at risk and affected and deaths. They should not be read as controlled contrasts: the study was not randomized, and no like-for-like control comparison is described. Event terms and percentages are not substitutes for endpoint estimates, a full safety analysis, or an analysis of comparative risk.

General: A dose-finding study can provide information about observed toxicity under its study conditions, while a randomized comparative trial is generally designed to estimate differences between assigned groups. Neither design label alone proves a clinical benefit or harm. In this case, the missing primary endpoint result prevents a numerical interpretation of DLT frequency from the registry record. The listed response outcomes likewise do not establish an observed tumor-response result.

Thus, the record supports understanding the study’s clinical question, design, endpoint definition and reported cohort safety entries. It does not support saying that AMG 256 did or did not work, stating which dose was selected, or estimating the precision of the primary outcome. No medical decision should be inferred from the registry entries alone.

14. Why This Trial Matters Statistically

This trial illustrates a statistical distinction between dose evaluation and randomized comparative research. The registry describes a sequential, non-randomized Phase 1 design intended to identify a maximum tolerated dose or recommended phase 2 dose. That design makes the definition and timing of a dose-limiting toxicity central to interpretation: the primary endpoint specifies both qualifying toxicities and a Day 1 to Day 28 observation window.

It also illustrates why an endpoint definition is not the same as an endpoint result. The registry provides a detailed description of which events qualify, but does not report the number of participants who experienced a DLT or the size of the evaluable population. Without those elements, a reader cannot estimate the observed frequency or its precision. The study-level enrollment cannot fill that gap because the primary analysis population is separately defined.

The non-randomized structure matters when reading cohort-level safety data. The cohorts describe participants within a sequential dose evaluation, not matched groups created by random assignment. Descriptive differences can be informative for understanding the record, but do not alone establish a dose-related causal effect or a comparative treatment effect.

The registry also lists multiple outcome measures, including drug exposure and response measures. This makes transparent analysis reporting important: readers need to know which outcomes were analyzed, how uncertainty was quantified, and whether multiplicity was addressed. Those analysis details are not reported in the registry record, which lists no analyses.

General: These features are common statistical challenges in early clinical development. Clear endpoint definitions, denominator reporting, and an explicit account of dose decisions allow readers to connect observations to the study question. Where those results and procedures are unavailable, the statistically sound interpretation is limited to what the record does report, rather than filling gaps by assumption.

15. 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 primary limitation for interpreting efficacy and safety is that the registry information does not report the primary DLT count, the size of the DLT Evaluable Set, or the dose-specific endpoint results. It also does not report which maximum tolerated dose or recommended phase 2 dose was selected. As a result, the main dose-selection outcome cannot be quantified from this record.

The design is non-randomized and unmasked. Cohort entries therefore do not provide a randomized control comparison, and differences between cohorts cannot be interpreted as causal treatment effects on the basis of the registry information alone. The registry does not report the dose levels, escalation algorithm, or decision rules, which further limits interpretation of how dose selection proceeded.

Although the registry lists 34 participants enrolled, it does not give the denominator for every endpoint or explain how many participants were evaluable for each analysis. Missing-data handling, analysis populations beyond the stated DLT Evaluable Set, and sensitivity analyses are not reported in the registry record. The record lists 16 outcome measures but no analyses, and does not report a multiplicity plan or statistical analysis plan.

Safety entries are presented by cohort with small reported at-risk counts. The term-specific serious adverse event percentages are listed without their denominators in the information. These details limit interpretation of precision and make it inappropriate to treat cohort differences or term percentages as stable comparative estimates. The listed information is useful for describing the registry record, but it is not a complete account of the trial’s statistical results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of AMG 256 in Adult Subjects With Advanced Solid Tumors — NCT04362748.
• Registry record last updated 2026-10-23; status last verified 2026-07.
• Results first posted 2026-10-23.
• 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.

19. Record Summary

NCT04362748 is a completed Phase 1 study of AMG 256 in adults with advanced solid tumors. The registry lists non-randomized allocation, no masking and a sequential design. Enrollment is listed as 34; the recorded start date is 2020-09-15 and the primary completion date is 2023-09-21.

The study’s primary endpoint was the number of participants with dose-limiting toxicities from Day 1 to Day 28, among participants who received at least one dose and had an evaluable endpoint. Dose escalation was intended to identify a maximum tolerated dose or recommended phase 2 dose, followed by dose expansion groups. The registry also lists pharmacokinetic and tumor-response outcomes.

The primary endpoint result, dose decision and listed secondary outcome results are not reported in the registry record. Cohort-level adverse event counts and terms are reported, but the study does not provide a randomized control comparison. The record lists no outcome analyses.