Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers (NCT03515551), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1: Number of Participants With Dose-limiting Toxicities.

2. Clinical Question

3. Trial Design

This was a first-in-human Phase I/II study of IMCnyeso, sponsored by Immunocore Ltd. The registry lists a non-randomized, unmasked, sequential design and enrollment of 29 participants. The listed study start was 2018-06-15, the primary completion date was 2021-05-10, and the status is terminated.

Phase I was a dose-escalation study intended to establish the maximum tolerated dose or recommended Phase 2 dose. Its seven cohorts included four fixed-dose escalation cohorts and three intrapatient dose-escalation cohorts. The cohort labels were 3 mcg, 10 mcg, 30 mcg, 100 mcg, 30-100 mcg, 30-100-180 mcg, and 30-100-300 mcg. The registry record does not state whether a maximum tolerated dose or recommended Phase 2 dose was established.

Phase II was planned as a dose-expansion stage with three cohorts treated at the recommended Phase 2 dose for a preliminary assessment of anti-tumor activity. Phase II was not initiated, and data were not collected. Consequently, the planned expansion cannot be interpreted as an observed phase of the trial or as a source of clinical activity results.

Because there was no randomized control group, differences between the dose cohorts would not provide a controlled treatment comparison. Participants were assigned within a sequential dose-escalation framework, and the registry record does not describe a concurrent comparator arm. It also does not report details of the sequence rules, escalation decisions, or stopping criteria.

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: There were a total of 28 unique participants; one participant from the 10 mcg cohort was sequentially enrolled in the 30-100 mcg cohort.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set includes all participants who received at least 1 full or partial 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.

Population: The Full Analysis Set includes all participants assigned to treatment who receive at least 1 full or partial dose of study drug; one participant that sequentially enrolled in two cohorts (10 mcg and 30-100 mcg) is represented in the 30-100 mcg cohort.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1: Number of Participants With Dose-limiting Toxicities, measured over Up to 35 months.

The primary endpoint was the number of Phase I participants with dose-limiting toxicities. It is a participant count: each participant is classified according to whether at least one qualifying event occurred during the specified evaluation period. The registry defines a qualifying event as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug. The event had to occur from the first dose through Day 28 after the first dose.

A dose-limiting-toxicity endpoint is used in dose escalation to describe clinically important toxicity within an early, prespecified assessment window. Such information can inform dose-selection decisions in an early-phase study. The registry describes the Phase I goal as establishing the maximum tolerated dose or recommended Phase 2 dose, but it does not report an endpoint count or a dose-selection conclusion.

The registry lists the endpoint timeframe as up to 35 months, while its event definition specifies the window for classifying a dose-limiting toxicity. These statements describe different aspects of the endpoint record; the detailed operational definition is the first-dose-to-Day-28 evaluation period. No primary endpoint result, estimate of uncertainty, or analysis method is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants with at least one qualifying dose-limiting toxicity. It is not a count of every separate event. For this type of binary outcome, each participant contributes an outcome classification: a qualifying event occurred or it did not. The registry defines the safety analysis set as participants who received at least 1 full or partial dose. The primary endpoint result itself is not reported in the registry record, so no event count or participant proportion can be interpreted from it.

Why does the endpoint have a defined time window?

The dose-limiting-toxicity definition restricts qualifying events to those occurring from the first dose up until Day 28 after the first dose. A fixed assessment window makes the endpoint definition more specific: events outside that window do not meet the stated timing criterion for this endpoint, even though they may be recorded as other safety outcomes. The registry lists the endpoint timeframe as up to 35 months, but does not explain how that broader timeframe relates operationally to the Day 28 classification window.

What can dose cohorts establish?

General statistical explanation: early dose-escalation studies describe safety as doses are increased or adjusted, with the intention of informing later dose selection. This design is not equivalent to a randomized comparison. In this study, the record identifies four fixed-dose cohorts and three intrapatient dose-escalation cohorts. Participants in different cohorts may have received different regimens, and the record does not provide randomization or a control group. Consequently, cohort-to-cohort count differences are descriptive rather than controlled estimates of dose effects. The rules used to escalate, hold, or stop doses are not reported in the registry record.

How should uncertainty be assessed?

General statistical explanation: a confidence interval describes a range of values compatible with an estimate under a specified statistical method; wider intervals indicate less precision. A p-value, when reported, measures compatibility of data with a defined null model and is not itself a measure of clinical importance. The registry record reports no confidence intervals, p-values, or model-based estimates for the primary endpoint. Since the primary count is also absent, its precision cannot be evaluated from this record. No inferential method for the primary endpoint is reported.

What do the planning assumptions mean?

The recorded sample-size planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a specified fraction of the observed effect. For time-to-event planning, the stated quantity is the total number of events using the Schoenfeld approach; for other outcomes, the stated quantity is participants per arm. These are planning assumptions, not a description of the trial's actual design: the trial was non-randomized, and the registry record does not report a sample-size justification for the trial. Any sample-size illustration based on an observed effect is a planning calculation, not observed power. General statistical explanation: power describes the chance of detecting a specified effect under stated assumptions; it cannot be inferred from enrollment alone.

Why does outcome type matter?

General statistical explanation: participant counts for binary outcomes are often expressed as event counts and denominators, while time-to-event outcomes incorporate event timing and censoring. A count does not convey when an event occurred, and it cannot substitute for a survival analysis. The registry lists progression-free survival, duration of response, and overall survival among secondary outcomes, but does not report analyses for them. No assumptions about censoring, follow-up completeness, or analysis models are reported in the registry record.

What is not documented?

The record lists 14 outcome measures and zero analyses. It does not report the statistical analysis plan, any interim analysis, the missing-data approach, or a multiplicity procedure. The absence of these details means that the intended tests, model choices, and handling of multiple outcomes cannot be reconstructed from the record. General statistical explanation: those decisions matter because analysis choices can affect estimates and uncertainty, while testing many outcomes can increase the chance of at least one apparently notable result. No such result should be inferred when analyses are not reported.

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("Phase 1: IMCnyeso 3 mcg", "Phase 1: IMCnyeso 10 mcg", "Phase 1: IMCnyeso 30 mcg", "Phase 1: IMCnyeso 100 mcg", "Phase 1: IMCnyeso 30-100 mcg", "Phase 1: IMCnyeso 30-100-180 mcg")
n      <- c(4, 3, 5, 3, 5, 4)
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  Phase 1: IMCnyeso 3 mcg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Phase 1: IMCnyeso 10 mcg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Phase 1: IMCnyeso 30 mcg  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Phase 1: IMCnyeso 100 mcg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Phase 1: IMCnyeso 30-100 mcg  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Phase 1: IMCnyeso 30-100-180 mcg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and zero analyses. The primary endpoint is the Phase I count of participants with dose-limiting toxicities. Listed secondary outcomes include Phase I best overall response, Phase I and Phase II progression-free survival, duration of response and overall survival, as well as pharmacokinetic measures. Phase II also had planned safety outcomes, but Phase II was not initiated and data were not collected.

The registry record does not report a multiplicity strategy, such as a hierarchy of endpoints or adjustment for testing multiple outcomes. General statistical explanation: when several outcomes or comparisons are tested, the chance of a false-positive finding can increase unless the analysis plan accounts for multiplicity. Because no outcome analyses are reported, there are no registry results for which an adjustment can be evaluated.

The safety analysis set is defined as participants who received at least 1 full or partial dose. The record does not report how missing endpoint assessments, incomplete follow-up, or participants without evaluable data were handled. It also does not describe an intention-to-treat population or another analysis population for efficacy outcomes. The enrollment count should not automatically be treated as the denominator for each outcome; outcome-specific denominators are not reported for the primary endpoint.

The record does not report the statistical analysis plan, interim-analysis methods, or the rationale for the planned sample size. These omissions limit assessment of prespecification and analysis choices. Their absence does not establish that no such plans existed; it means they are not reported in the registry record.

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: abdominal pain (33.3%), cytokine release syndrome (33.3%), epistaxis (33.3%), intra-abdominal haemorrhage (25.0%), lung infection (25.0%).

The registry lists serious adverse-event counts by Phase I dose cohort. The affected/at-risk counts are 3 among 4 at 3 mcg, 1 among 3 at 10 mcg, 1 among 5 at 30 mcg, 1 among 3 at 100 mcg, 2 among 5 at 30-100 mcg, 3 among 4 at 30-100-180 mcg, and 3 among 5 at 30-100-300 mcg. These are descriptive cohort counts, not randomized comparisons.

The registry also lists deaths by cohort: 4, 1, 2, 2, 2, 4, and 1, respectively, in the same cohort order. It does not report their causes, timing, or relationship to study drug. These counts should not be interpreted as treatment-attributed deaths.

Listed serious adverse-event terms include abdominal pain, cytokine release syndrome, and epistaxis, each at 33.3%; intra-abdominal haemorrhage, lung infection, and overdose, each at 25.0%. The denominator behind these percentages and event-level attribution are not reported in the registry record. General statistical explanation: serious-event percentages are most interpretable alongside their denominators and definitions; percentages alone do not show the precision of an estimate.

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

The record documents a first-in-human, non-randomized Phase I dose-escalation study of IMCnyeso in a selected population with advanced cancers positive for NY-ESO-1 and/or LAGE-1A and HLA-A*02:01-positive status. It describes planned dose cohorts and a primary safety endpoint based on dose-limiting toxicities occurring within the specified early evaluation period. It also records serious adverse events and deaths by cohort.

However, the primary endpoint count is not reported, and the registry lists zero analyses. The adverse-event summaries are descriptive entries rather than estimates from a randomized comparison. The record does not report the event timing, causes of death, or attribution details needed to interpret those entries as evidence of a specific treatment effect. No confidence intervals or other uncertainty measures are reported.

The planned Phase II expansion was not initiated and data were not collected. Therefore, the planned preliminary assessment of anti-tumor activity is unavailable in this record. Although response and survival outcomes appear among the listed outcomes, the record does not provide analyzed results for them. The study description alone cannot answer whether those outcomes changed during treatment.

These limitations do not establish that an outcome did or did not occur. They define what can be concluded from the registry record: study structure, planned endpoints, selected cohort-level safety counts, and the fact that the planned Phase II expansion did not proceed. General statistical explanation: estimates require both observed data and a defined analysis; uncertainty measures help show how precise those estimates are. Without reported primary endpoint results or analyses, neither the size nor precision of a treatment-related effect can be assessed.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between an early dose-escalation objective and a later expansion objective. Phase I was intended to characterize dose-limiting toxicities and establish a maximum tolerated dose or recommended Phase 2 dose. Phase II was planned to assess anti-tumor activity at the recommended Phase 2 dose, but it was not initiated. The two stages therefore represent different questions, and the planned Phase II objective should not be mistaken for a completed efficacy assessment.

It also illustrates why the design matters when reading cohort data. The study was non-randomized, unmasked, and sequential, with multiple dose schedules rather than a control arm. Counts across those cohorts can describe recorded events, but do not provide a like-for-like causal comparison. Variation in cohort counts alone cannot identify the effect of dose.

Finally, the registry record distinguishes study registration details from a complete statistical report. It describes outcomes and analysis populations, but lists zero analyses and does not report the primary endpoint result, a sample-size justification, multiplicity methods, or missing-data handling. General statistical explanation: estimates and their uncertainty are needed to assess how much the observed data support a conclusion and how precise that conclusion is. Their absence makes disciplined interpretation important, especially when the record includes several planned outcomes but no reported inferential results.

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 most direct limitation of the registry record is that it does not report the primary endpoint count or any analyses. Enrollment is listed as 29, but the number included in the safety analysis set and the endpoint-specific denominator are not reported. The registry defines the safety analysis set but does not give the number of participants meeting that definition.

The study had no randomized comparator and was unmasked. Its cohorts followed different dose schedules, so their descriptive counts cannot be treated as controlled estimates of comparative safety or efficacy. The registry does not report dose-escalation rules, decisions about progression between cohorts, or the rationale for sample size.

Phase II was not initiated, and its planned data were not collected. The record therefore contains no Phase II expansion results. For the listed serious adverse events and deaths, timing, causes, relationship to study drug, and relevant event-specific denominators are not reported. The registry also does not provide confidence intervals, p-values, statistical models, a multiplicity procedure, missing-data methods, or interim-analysis information.

These are limitations of what is reported in the registry record; they do not establish that the details or analyses were absent from other study materials. General statistical explanation: without denominators, analysis methods, and uncertainty measures, it is difficult to assess how stable a descriptive count is or how broadly it may apply. The record supports description of the registered design and posted counts, but not a complete quantitative assessment of treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of IMCnyeso in Advanced NY-ESO-1 and/or LAGE-1A Positive Cancers — NCT03515551.
• Registry record last updated 2022-03-11; status last verified 2022-03.
• Results first posted 2022-03-11.
• 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

NCT03515551 is a terminated Phase I/II study sponsored by Immunocore Ltd, with enrollment of 29. It evaluated IMCnyeso in HLA-A*02:01-positive adults with advanced NY-ESO-1 and/or LAGE-1A positive cancer. The study was non-randomized, unmasked, and sequential.

Phase I used seven dose-escalation cohorts and had a primary endpoint of participants with dose-limiting toxicities. The registry record does not report the primary endpoint result and lists zero analyses. Phase II was planned as a dose expansion but was not initiated, and data were not collected. Serious adverse-event counts and deaths are listed by Phase I cohort, but their attribution and several details needed for interpretation are not reported.