A Study of Nanrilkefusp Alfa (SOT101) in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Nanrilkefusp Alfa (SOT101) in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer (NCT05619172), a non-randomized phase 2 study. The primary outcome is Objective Response Rate According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1).

2. Clinical Question

The study asked whether nanrilkefusp alfa, given with cetuximab, showed antitumor activity in patients with RAS wild-type colorectal cancer. Its primary objective was to estimate efficacy for the combination. The primary endpoint was objective response rate under RECIST 1.1: the proportion of participants assessed as having a complete or partial response in target lesions by CT or MRI.

The question was studied in a Phase 2, open-label, non-randomized, single-arm trial. The registry describes sequential treatment cohorts at nanrilkefusp alfa doses of 9 µg/kg and 12 µg/kg, each in combination with cetuximab. It does not describe a concurrent control group. Consequently, the central efficacy question is descriptive: what response proportion was observed among participants receiving the combination, rather than whether the combination outperformed another treatment in a randomized comparison.

The primary endpoint timeframe was Day 1 up to approximately 1 year 2 months. Participants with missing response data were counted as non-responders under the stated endpoint definition. Numerical response results and the endpoint’s confidence interval are not reported in the registry record, so the magnitude and precision of the observed response proportion cannot be assessed from this record.

3. Trial Design

This was a Phase 2, open-label, multicenter study of nanrilkefusp alfa with cetuximab in patients with RAS wild-type colorectal cancer. Its allocation is listed as non-randomized, its masking as none, and its model as sequential. The registry identifies two dose cohorts: nanrilkefusp alfa 9 µg/kg with cetuximab and nanrilkefusp alfa 12 µg/kg with cetuximab. The stated total enrollment was 16.

Sequential cohorts and the absence of randomization matter when interpreting comparisons. Participants were not assigned by random allocation to a treatment or control group, and no concurrent control arm is described. Differences between cohort outcomes, if reported, could reflect differences in participants, timing, or other factors as well as dose. The registry explicitly says results are presented in aggregate and that there was no plan to analyze cohorts separately. The cohort labels should therefore not be treated as evidence from a controlled dose comparison.

The study began on 2022-12-22, had a primary completion date of 2024-03-06, and is listed as terminated. The reason for termination is not reported in the registry record. The record does not describe a protocol-based reason for the sequential dose structure, any enrollment targets by cohort, or whether enrollment ended as planned.

The primary endpoint was objective response rate according to RECIST 1.1. The listed timeframe ran from Day 1 up to approximately 1 year 2 months. Secondary outcomes include response assessment by iRECIST and best overall response categories under RECIST 1.1 and iRECIST. The registry lists 31 outcome measures, but numerical primary and secondary outcome findings are not reported in the registry record. It lists zero analyses.

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.

Safety Cohort 1

Reasons for not completing this period:

Safety Cohort 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per statistical considerations outlined in the trial Protocol and Statistical Analysis Plan, all patients were analyzed within pre-specified populations across the entire trial. There was no plan to analyze cohorts separately; therefore, results are presented in aggregate. The trial was a single-arm design, not a classic dose-escalation study, as the RP2D (12 µg/kg) had been established in a prior trial (NCT04234113). The 9 µg/kg dose was a safety cohort allowing one-way crossover to 12 µg/kg.

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 Objective Response Rate According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1), measured over Day 1 up to approximately 1 year 2 months.

Objective response rate is the proportion of participants whose tumors meet the defined criteria for complete or partial response. In this trial, the definition refers to target lesions assessed by CT or MRI and classified according to RECIST 1.1. Complete response and partial response are distinct categories, but both count toward the stated endpoint. Participants with missing data were classified as non-responders.

Response rate is used to describe the frequency of tumor shrinkage that meets prespecified criteria. It is a proportion, not a time-to-event measure: it does not by itself describe how long a response lasts, how long participants live, or how symptoms change. Its interpretation depends on the assessment criteria, evaluation schedule, analysis population, and handling of missing assessments. The registry gives the endpoint timeframe as Day 1 up to approximately 1 year 2 months.

In a single-arm study, a response proportion describes outcomes among participants who received the study combination. Without a randomized comparator, it cannot establish how that proportion differs from outcomes under another treatment or from what would have occurred without the combination. The registry record does not report the observed response proportion or its 95% confidence interval, so it is not possible to evaluate the estimated response rate or its statistical precision from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a Phase 2, open-label, non-randomized, sequential, single-arm study. These design terms shape the statistical interpretation. Phase 2 describes the study’s phase; it does not itself establish efficacy. Open-label means masking is listed as none, so the record does not describe blinded treatment assignment or assessment. Non-randomized means treatment allocation was not randomized. Single-arm means the record does not describe a concurrent control group. Sequential refers to the listed cohort model, but further details of the sequencing process are not reported in the registry record.

What does a response proportion estimate?

Objective response rate is a binary outcome at the participant level: a participant either meets the endpoint definition for complete or partial response, or does not. The endpoint is defined as the proportion of participants meeting either response category under RECIST 1.1, with target lesions assessed by CT or MRI. The registry says missing data were treated as non-response. This rule makes the handling of missing assessments explicit for the primary endpoint, although the amount and pattern of missing response data are not reported in the registry record.

A proportion is an estimate of the response frequency in the analyzed participants. A confidence interval expresses statistical uncertainty around an estimate; it is not a guarantee that the true value lies within a particular observed range. Its width depends on the information in the data and the method used. The registry specifies a 95% confidence interval for the primary endpoint, but does not report its numerical bounds. Therefore, the estimate and its precision cannot be evaluated from the registry record.

Why does the lack of randomization matter?

Random allocation helps make comparison groups similar, on average, in both measured and unmeasured characteristics. Without random allocation and a control arm, the response rate describes outcomes observed after the combination but does not estimate a randomized between-group contrast. In general, observed outcomes in a single-arm study can reflect participant characteristics, other care, assessment practices, and the natural course of disease as well as the treatment under study. Those are general limitations of the design, not findings about this particular trial.

The registry identifies sequential dose cohorts of 9 µg/kg and 12 µg/kg, each with cetuximab. Sequential enrollment is not equivalent to random assignment between dose groups. Participants in cohorts enrolled at different points can differ for reasons other than dose, and the record does not report a cohort-specific randomized analysis. It states that analysis was planned in prespecified populations across the entire trial, with results presented in aggregate rather than separately by cohort.

What can the stated analysis population tell us?

The primary endpoint description says the analysis followed prespecified populations across the entire trial, but the available wording does not name or define each population. The statistical plan and protocol details are not reported in the registry record. It is therefore not possible to determine from this entry exactly who was included in each analysis population, how eligibility for those populations was decided, or whether any participants were excluded from a particular analysis.

Counting participants with missing data as non-responders is a conservative classification in the limited sense that missing outcomes do not count as responses. It is not a complete solution to missing-data uncertainty. If missing assessments are related to prognosis, treatment discontinuation, or disease status, the resulting proportion may differ from what would have been observed with complete follow-up. The registry does not report the number of participants with missing primary endpoint data or reasons for missingness.

How should dose cohorts be read?

Both cohorts received cetuximab alongside nanrilkefusp alfa, and the registry says outcomes are presented in aggregate. Aggregate reporting addresses the trial’s overall enrolled population as described in the statistical considerations, but it does not show whether outcomes differed by cohort. Even if cohort-specific values were available, non-randomized sequential cohorts would not automatically support a causal dose comparison. The record does not report a separate cohort analysis.

The term “confidence interval” in the endpoint definition identifies the uncertainty measure intended for the response estimate. It should be distinguished from a hypothesis test or a comparison with a benchmark. The record does not report a numerical estimate, interval, comparison test, or benchmark for the primary endpoint. It also lists zero analyses, so no primary endpoint inferential result is available to interpret.

What can planning calculations say?

Sample-size illustrations based on an observed effect are planning scenarios, not evidence that a trial had a particular probability of success. General planning calculations describe the enrollment that might be needed under stated assumptions to detect a chosen effect with a chosen power. The registry record does not report a trial-specific sample-size justification, and any illustrative planning values do not represent observed power or additional participants actually enrolled. The assumptions described for such illustrations include a two-sided significance level of 0.05, equal allocation, and a normal approximation. These are features of the stated planning illustration, not a reported analysis plan for this study.

Over-dispersion is a general concern when observed variability is greater than a model assumes; it can make standard errors and confidence intervals too small if not accounted for. It is not a reported issue or analysis feature in this registry record. More broadly, details of the statistical methods beyond the endpoint definition, the confidence-interval label, the analysis-population statement, and the listing of zero analyses are not reported in the registry record. No additional model, adjustment, interim analysis, or multiplicity procedure should be inferred.

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("Nanrilkefusp Alfa and Cetuximab")
n      <- c(16)
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  Nanrilkefusp Alfa and Cetuximab  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 31 outcome measures, including the primary objective response rate under RECIST 1.1 and secondary outcomes involving iRECIST and best overall response categories under RECIST 1.1 and iRECIST. When a study evaluates multiple outcomes, there can be more opportunities for an apparently notable result to arise by chance. Statistical approaches can control or describe this multiplicity, but the approach planned for this trial is not reported in the registry record. No adjustment should be assumed.

The primary endpoint definition explicitly states that participants with missing data were considered non-responders. This rule clarifies how missing primary response assessments were classified. The number of participants with missing endpoint data, the reasons for missingness, and the amount of follow-up available are not reported in the registry record. The treatment of missing data for each secondary outcome is also not reported.

The primary outcome description refers to prespecified populations across the entire trial and says the results are presented in aggregate, with no plan to analyze cohorts separately. The names and detailed definitions of those populations are not reported in the registry record. It is therefore not possible to assess exactly which participants were included in the primary analysis or how protocol deviations and discontinuations were handled.

The record lists zero analyses, and numerical primary and secondary outcome findings are not reported. It does not report a statistical analysis plan, interim analyses, a sample-size justification, or a multiplicity procedure. These omissions limit assessment of how the planned analyses were executed and how much inferential weight any outcome was intended to carry.

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: malignant neoplasm progression (50.0%), disease progression (14.3%), alanine aminotransferase increased (7.1%), aspartate aminotransferase increased (7.1%), blood bilirubin increased (7.1%).

The safety record separates serious adverse events from other adverse events by the listed treatment cohort. For the 9 µg/kg nanrilkefusp alfa and cetuximab safety cohort, the serious-event risk denominator is 14 and 7 participants were affected; the other-event denominator is 14 and 14 participants were affected. The record lists 7 deaths for that cohort. For the 12 µg/kg cohort, the serious-event denominator is 2 and 1 participant was affected; the other-event denominator is 2 and 2 participants were affected. The record lists 1 death for that cohort.

These are counts within the registry’s safety reporting, not a randomized comparison of treatments. The cohorts differ in size and were not assigned through randomization, so their event counts should not be compared as if they came from equivalent control groups. A participant count does not communicate event severity, duration, timing, or whether a participant experienced multiple events. The registry record does not report enough detail to determine the causal relationship of the listed deaths or events to study treatment.

The most frequent listed serious-event terms include malignant neoplasm progression at 50.0%, disease progression at 14.3%, and alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, and general physical health deterioration, each at 7.1%. These percentages are registry-listed serious-event terms; the record does not provide the term-specific participant counts in this summary. Safety figures describe reported events and should not be interpreted as proof that treatment caused an event or as a comparison of risk against another treatment.

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

The registry record identifies a study intended to estimate antitumor efficacy for nanrilkefusp alfa combined with cetuximab in RAS wild-type colorectal cancer. It specifies objective response rate according to RECIST 1.1 as the primary endpoint and explains that missing data were counted as non-response. It also describes the trial as Phase 2, open-label, non-randomized, sequential, and single-arm.

Those details establish what the study set out to measure and the context for interpreting a response estimate. They do not supply the numerical estimate. The observed response proportion and its 95% confidence interval are not reported in the registry record. As a result, the posted results do not establish how many participants responded, how large the estimated response frequency was, or how precisely it was measured.

Even if a response estimate were available, a single-arm study would not by itself show how the combination compares with a control treatment. The study does not describe random assignment or a concurrent control group. Outcomes therefore could not be interpreted as a randomized treatment contrast. The registry’s aggregate-analysis statement also means the record does not provide a planned separate efficacy analysis for the 9 µg/kg and 12 µg/kg cohorts.

The safety counts provide descriptive information for the listed cohorts, including participants affected by serious and other adverse events and deaths. They do not establish treatment causation, and the unequal cohort sizes and non-randomized design prevent a like-for-like comparative safety conclusion. The reason the study was terminated is not reported in the registry record; termination status alone does not establish why the study ended or what its efficacy findings were.

In short, the record supports a description of the study design, endpoint definition, and selected safety counts. It does not support a numerical assessment of primary efficacy or a controlled comparison of benefit and risk. Missing numerical outcome results and limited analysis details are central to the interpretation, rather than evidence in favor of either a positive or negative efficacy conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable because it illustrates the difference between defining an efficacy question and reporting evidence that answers it. The registry specifies a clinically interpretable endpoint: the proportion of participants with complete or partial response by RECIST 1.1. It also names the imaging assessment approach, the assessment timeframe, the treatment of missing data, and the use of a 95% confidence interval. Those details make the intended outcome understandable.

However, an endpoint definition is not an endpoint result. Without the observed response proportion and confidence interval, readers cannot assess the response frequency or its precision. This distinction is especially important when an entry contains substantial design and endpoint information but no numerical primary outcome finding.

The design also illustrates why a response rate from a single-arm study answers a narrower question than a randomized comparison. The response rate would describe participants treated with the combination; it would not establish the treatment’s effect relative to a concurrent control. The sequential cohorts do not remove that limitation, because randomization between dose groups is not described and the registry says results are presented in aggregate.

Finally, the trial’s listed status and safety summaries should not be treated as substitutes for efficacy results. Termination does not explain the reason for stopping, and adverse-event counts do not establish causality. Together, these features highlight the importance of distinguishing descriptive findings, comparative evidence, and missing outcome information when reading clinical trial records.

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 for interpreting efficacy is that the numerical primary endpoint result is not reported in the registry record. The record specifies the endpoint and its confidence interval format but does not give the response count, response proportion, or interval bounds. Numerical secondary outcome results are also not reported. The record lists zero analyses.

The study was non-randomized, open-label, and single-arm, with no concurrent control group described. Any observed response proportion would therefore be descriptive and could not provide a randomized estimate of comparative treatment effect. The sequential dose cohorts are not a like-for-like control comparison, and the registry says results are presented in aggregate rather than separately by cohort.

The enrollment was 16. The registry does not report a trial-specific sample-size justification, nor does it give enough numerical efficacy information to assess the precision of an observed response estimate. The stated confidence interval is not itself a numerical result. Details of interim analyses, further statistical methods, and the analysis populations are not reported in the registry record.

Although missing primary endpoint data were classified as non-response, the number of missing assessments and reasons for missingness are not reported. The specific handling of missing data for secondary outcomes is also not reported. The record lists 31 outcome measures but does not report a multiplicity procedure, limiting assessment of how multiple outcomes were addressed.

The trial is listed as terminated, but the reason for termination is not reported in the registry record. The safety summary provides event denominators and affected-participant counts, but does not establish treatment causality. These limitations mean the entry supports a description of trial structure and selected safety reporting, not a complete appraisal of efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Nanrilkefusp Alfa (SOT101) in Combination With Cetuximab to Evaluate the Efficacy and Safety in Patients With Colorectal Cancer — NCT05619172.
• Registry record last updated 2025-07-24; status last verified 2025-07.
• Results first posted 2025-07-24.
• 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

NCT05619172 is a Phase 2, open-label, non-randomized, sequential, single-arm study of nanrilkefusp alfa with cetuximab in patients with RAS wild-type colorectal cancer. It lists 16 participants enrolled and two dose cohorts: 9 µg/kg and 12 µg/kg of nanrilkefusp alfa, each with cetuximab. The study began on 2022-12-22, had a primary completion date of 2024-03-06, and is listed as terminated.

The primary endpoint is objective response rate by RECIST 1.1, defined using complete or partial response in target lesions assessed by CT or MRI. Missing endpoint data were counted as non-response. The registry says results were analyzed in aggregate rather than separately by cohort.

Numerical primary and secondary efficacy findings are not reported in the registry record. The record lists safety counts by cohort and zero analyses, but does not report the reason for termination or a randomized comparison.