AMG 102 and Erlotinib for Advanced Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AMG 102 and Erlotinib for Advanced Non-Small Cell Lung Cancer (NCT01233687), a na phase 1, phase 2 study. The primary outcome is Percentage of Participants That Experienced a Dose Limiting Toxicity.

2. Clinical Question

The clinical question is primarily about safety and dose selection, rather than a comparison of the combination against another treatment. The study also planned to examine whether the combination warranted further interest in this patient population. Objective response rate, progression-free survival and overall survival are listed as secondary outcomes, but their numerical results are not reported in the registry record.

3. Trial Design

This was a phase I/II study of AMG 102 and erlotinib in previously treated patients with advanced non-small-cell lung cancer. The registry classifies the study as single group, with allocation not applicable and no masking. These design features mean that the record does not describe a randomized comparison or a blinded control group. The posted treatment arm is the combination of AMG 102 and erlotinib.

The study description divides the work into a phase I part and a phase II part. The phase I part was intended to assess safety and identify a recommended dose for the phase II part. The phase II part was intended to assess whether the combination merited further interest. The planned enrollment ranges in the description are 8-16 participants for phase I and 21-45 for phase II. The registry lists enrollment of 49, but does not report how enrollment was distributed between the two parts.

Participants were described as having recurrent or progressive advanced disease after at least one and no more than two prior chemotherapy regimens. The primary outcome concerns dose-limiting toxicity during the first cycle of treatment, defined as 3 weeks in the record. The registry's primary-outcome text states that, in the absence of dose-limiting toxicities among the first 7 participants treated, AMG 102 with erlotinib (150 mg) daily for 3 weeks was declared the recommended phase II dose.

There is no like-for-like control group in this design. Any interpretation should therefore focus on the reported experience in the treated group, rather than on a causal difference between treatments. Details of the protocol, including the full dose-escalation procedures and the statistical plan, are not reported in the registry record.

4. Participant Flow and Accounting

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

Phase I RP2D AMG 102 + Erlotinib

Phase II AMG 102 + Erlotinib

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: In the absence of DLTs among the first 7 pts treated, AMG 102 + Erlotinib (150 mg) daily (3 weeks) was declared the RP2D.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants That Experienced a Dose Limiting Toxicity, measured over During first cycle of treatment (3 weeks).

The primary endpoint is the percentage of participants who experienced a dose-limiting toxicity. The registry specifies the assessment timeframe as the first treatment cycle, which is 3 weeks. It also identifies a 90% confidence interval as the measure of dispersion for the outcome. A numerical percentage, event count and confidence interval are not reported in the registry record.

This endpoint is used to characterize tolerability during early treatment and to support dose selection in the phase I part of the study. A dose-limiting toxicity is an event considered significant for decisions about whether a dose is suitable for further study; the registry's detailed criteria for classifying such events are not reported. The primary-outcome description links the safety assessment to determining the recommended phase II dose.

In general, a percentage expresses the share of an assessed group with the event, while a confidence interval describes uncertainty around an estimated percentage. The interval does not remove uncertainty or establish that the estimate applies to other populations. Here, the record names a 90% confidence interval but does not provide its bounds, so the precision of the primary endpoint cannot be assessed from the registry record.

The endpoint is distinct from the secondary outcomes of objective response rate, progression-free survival and overall survival. Those outcomes address clinical response and time-to-event experience, whereas the primary endpoint is focused on toxicity during the first cycle. Numerical results for the secondary outcomes are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as a percentage of participants with an event and specifies a 90% confidence interval. It does not provide the primary outcome's numerical estimate or interval bounds. The registry also lists no analysis records, so the analytical procedures used for the primary and secondary outcomes are not reported in the registry record.

What does a percentage estimate?

In general, an event percentage describes the proportion of an assessed group that experienced a defined event. Its interpretation depends on how the event is defined, which participants are included, and what period of follow-up is used. For this primary outcome, the event is a dose-limiting toxicity and the stated period is the first treatment cycle of 3 weeks. The registry does not report the event count, the number included in the primary analysis, or the operational criteria used to classify a toxicity as dose-limiting. Without those details and the numerical estimate, the reported endpoint cannot be independently checked from the registry record.

What does a confidence interval contribute?

In general, a confidence interval conveys statistical uncertainty around an estimate. A narrower interval indicates greater precision under the assumptions of the method used; a wider interval indicates less precision. The registry specifies a 90% confidence interval for the primary endpoint, but does not give its lower or upper bound. Naming an interval level without reporting the interval itself does not show how precise the outcome estimate is. The method used to calculate the interval is also not reported in the registry record.

Why does the single-group design matter?

In general, a single-group study describes outcomes among participants receiving the study treatment, rather than directly estimating a difference against a concurrent control group. The record classifies this trial as single group, with allocation not applicable and masking none. Thus, a numerical outcome in this design would characterize the treated group, but it would not by itself establish what would have happened to the same participants under a different treatment. Differences in patient characteristics, disease course, other care or assessment can matter when interpreting uncontrolled outcomes. These are general considerations, not additional reported findings from this trial.

The phase I and phase II aims also differ. The study description says the phase I part was designed to assess safety and determine a recommended dose for phase II, while phase II was intended to assess whether the combination warranted further interest. The primary outcome is aligned with the safety and dose-selection aim. The registry's statement about declaring the recommended phase II dose refers to the absence of dose-limiting toxicities among the first 7 participants treated and the specified combination dose. Details of the dose escalation method, decision rules, and any subsequent dose cohorts are not reported in the registry record.

How should event counts and rates be read?

In general, a count reports how many participants had an event, while a percentage expresses an event frequency relative to a stated denominator. The registry lists 18 participants affected among 45 at risk for serious adverse events. For other adverse events, it lists 45 affected among 45 at risk. It also gives percentages for selected serious adverse event terms. The registry does not explain whether terms could overlap within a participant or provide further detail about the methods used to collect and classify events. These safety summaries do not establish a comparative risk because no control group is listed.

Over-dispersion is a general statistical concern when observed variation exceeds what a simple probability model assumes. It can make standard errors and confidence intervals too small if the analysis assumes less variability than the data contain. Whether over-dispersion was relevant to any trial outcome, and whether an adjustment was made, are not reported in the registry record. It should not be assumed that such an issue occurred or that a particular method was used.

The record lists objective response rate, progression-free survival and overall survival as secondary outcomes. In general, time-to-event analyses account for the fact that participants may have different lengths of observation and may not experience the event during follow-up. The registry does not provide numerical results, censoring details, analysis populations or methods for these secondary endpoints. Therefore, no specific time-to-event procedure can be attributed to this study from the registry record.

Planning calculations described for the accompanying statistical material use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the target effect is defined as a fraction of the observed effect. In general, such calculations illustrate hypothetical sample-size requirements under chosen assumptions. They are not observed power and do not describe the original trial's design. In particular, the trial itself is recorded as single group, and its protocol-based sample-size justification is not reported in the registry record.

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("AMG 102 + Erlotinib")
n      <- c(7)
events <- c(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  AMG 102 + Erlotinib  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome as the percentage of participants experiencing a dose-limiting toxicity. It also lists objective response rate, progression-free survival and overall survival as secondary outcomes, and records five outcome measures overall. The statistical analysis records are listed as zero. A prespecified strategy for controlling multiplicity across outcomes or analyses is not reported in the registry record.

In general, testing multiple outcomes or conducting multiple analyses can increase the chance of obtaining an apparently notable result by chance. Multiplicity procedures can define how evidence is evaluated across such tests. Without a reported analysis plan, it is not possible to determine whether a correction was planned, whether outcomes were ordered hierarchically, or whether the secondary outcomes were intended to support confirmatory conclusions. No particular strategy should be inferred.

Missing-data handling is also not reported in the registry record. The record does not describe how participants with incomplete outcome assessments were handled, whether all enrolled participants were included in each analysis, or how missing values were treated. For the primary endpoint, it does not report the analysis denominator or a numerical event estimate. The safety figures do include denominators of 45 at risk for serious adverse events and 45 at risk for other adverse events, but the registry does not explain how those safety populations relate to the enrollment of 49.

Analysis populations are not described in detail. The record does not state whether the outcomes were analyzed according to an intention-to-treat principle, a treated population, or another defined group. It also does not provide a participant flow account linking enrollment to the populations assessed for each endpoint. These omissions limit assessment of how complete and comparable the outcome data were across the study.

12. Safety Results

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

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: dyspnea (11.1%), thromboembolic event (8.9%), anemia (2.2%), diarrhea (2.2%), mucositis oral (2.2%).

The registry reports 45 participants at risk for serious adverse events and 18 affected in the AMG 102 plus erlotinib group. For other adverse events, it reports 45 at risk and 45 affected. These are safety summaries for the single treatment group; the registry does not list a separate control group for comparison. The reason the safety denominator is 45 while overall enrollment is listed as 49 is not reported in the registry record.

The most frequently listed serious adverse event terms are dyspnea at 11.1% and thromboembolic event at 8.9%. Anemia, diarrhea, oral mucositis and nausea are each listed at 2.2%. The registry does not provide further detail about event severity grading, duration, overlap between event terms, or the method used to determine the percentages. The death count is not reported in the registry record.

In general, serious adverse event summaries describe events meeting the applicable reporting definition; they are not interchangeable with all adverse events or with dose-limiting toxicities. The registry does not establish that the serious adverse events listed were dose-limiting. Because the study has no control group, these figures describe reported events in the treated group and do not estimate how event rates compare with another treatment.

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

The record describes a phase I/II investigation of AMG 102 with erlotinib in previously treated patients with advanced non-small-cell lung cancer. Its primary outcome focuses on dose-limiting toxicity during the first 3-week treatment cycle, reflecting the safety and dose-selection purpose of the phase I part. The registry's primary-outcome text states that, in the absence of dose-limiting toxicities among the first 7 participants treated, the combination with erlotinib at 150 mg daily for 3 weeks was declared the recommended phase II dose.

That statement does not provide a complete numerical primary-outcome result. The registry does not report the primary endpoint percentage, event count, confidence interval bounds, or details of the population used for its calculation. It therefore does not allow readers to assess the estimate's precision or reconstruct the outcome from the registry record.

The record also lists serious adverse event counts and percentages for selected terms. Those figures describe the safety reporting for the single treatment group. They do not show how the combination compares with another treatment, and the registry does not report the death count. The relationship between the safety denominator and total enrollment is also not explained.

Objective response rate, progression-free survival and overall survival are named as secondary outcomes. Their numerical results are not reported in the registry record, so the magnitude and precision of those outcomes cannot be assessed from this information. More broadly, the study design lacks a concurrent randomized comparator, and the registry provides no detailed analysis plan or account of missing data and analysis populations.

Accordingly, the record documents the study's aims, design, dose-selection statement and selected safety summaries, but it does not provide enough numerical outcome information to quantify the primary endpoint or evaluate the listed secondary outcomes. These limitations are about what the registry record reports; they should not be interpreted as evidence that unreported assessments were not conducted.

14. Why This Trial Matters Statistically

This trial is statistically notable for linking an early-phase safety endpoint with dose selection. The primary measure is the percentage experiencing dose-limiting toxicity during the first treatment cycle, and the study description identifies the phase I aim as determining safety and a recommended dose for phase II. That differs from a design whose primary purpose is to estimate a comparative treatment effect.

The registry records a single-group study with no masking and allocation marked not applicable. That design is consistent with describing outcomes among participants receiving the combination, but it does not supply a randomized control estimate. This distinction matters when readers interpret observed safety events or any other outcomes: a result in one group is not itself a comparison against what would have occurred under another treatment.

The record's dose-selection statement is a useful example of a decision rule being discussed alongside an endpoint, but important statistical details remain unreported. The primary outcome's numerical estimate and stated confidence interval are absent, and the registry lists no analysis records. The complete dose escalation procedures and analysis populations are also not reported. Those gaps make it difficult to judge the uncertainty around the endpoint or trace how the dose decision followed from the collected data.

There is also a distinction between the trial's actual design and generic planning illustrations. The record identifies the trial as single group, while the stated planning assumptions describe equal allocation between two arms. Such calculations can be useful as hypothetical illustrations under their assumptions, but they are not the trial's design, an observed power estimate, or evidence that the study was planned using those assumptions. The trial's own sample-size justification is not reported in the registry record.

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 registry record does not report a numerical primary-outcome estimate, event count or bounds for the specified 90% confidence interval. Although the primary-outcome text includes a dose-selection statement referring to the absence of dose-limiting toxicities among the first 7 participants treated, it does not provide the full numerical result or explain the decision procedure in detail. The criteria used to define a dose-limiting toxicity are not reported.

The single-group design has no concurrent comparator, and the record lists no masking. Consequently, outcomes describe the treatment group and cannot establish a comparative difference against another treatment. The registry does not provide a detailed account of how participants were allocated across the phase I and phase II parts, or how the reported enrollment of 49 was distributed between them.

For safety, the record reports 45 participants at risk for serious adverse events and 18 affected, as well as 45 at risk and 45 affected for other adverse events. It does not explain how those denominators relate to enrollment, whether event terms could overlap, or how events were assessed. A death count is not reported. Numerical results for objective response rate, progression-free survival and overall survival are also not reported in the registry record.

Further limitations include the absence of a reported statistical analysis plan, analysis populations, missing-data procedures and multiplicity strategy. The registry lists no analysis records. Protocol details and a trial-specific sample-size justification are not reported, so neither the precision of the primary estimate nor the basis for the planned enrollment can be evaluated from this record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: AMG 102 and Erlotinib for Advanced Non-Small Cell Lung Cancer — NCT01233687.
• Registry record last updated 2017-06-22; status last verified 2017-05.
• Results first posted 2016-09-01.
• 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.

19. Record Summary

The registry describes a completed phase I/II, single-group study of AMG 102 and erlotinib in previously treated patients with advanced non-small-cell lung cancer. It lists enrollment of 49 and no masking. The primary outcome is the percentage of participants with a dose-limiting toxicity during the first treatment cycle of 3 weeks, with a 90% confidence interval specified.

The primary-outcome text states that, in the absence of dose-limiting toxicities among the first 7 participants treated, AMG 102 with erlotinib (150 mg) daily for 3 weeks was declared the recommended phase II dose. A numerical primary-outcome estimate and interval are not reported in the registry record. Serious adverse event information includes 18 affected among 45 at risk; numerical results for the listed secondary outcomes are not reported. The registry lists no analysis records, and detailed statistical methods, missing-data procedures and analysis populations are not reported.