VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer (NCT05374538), a non-randomized phase 1 study. The primary outcome is Incidence of Treatment Emergent Adverse Events (Safety and Tolerability).

2. Clinical Question

The study was intended to examine VIC-1911 as monotherapy and in combination with sotorasib in people with locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer. The registry describes dose-escalation and expansion cohorts, including different prior-treatment histories for the combination groups. However, the monotherapy dose-escalation cohort treated no subjects, and the expansion phase did not open. The only opened dose level was in the combination dose-escalation cohort.

This distinction is central to interpreting the clinical question. The registry’s broad study description encompasses more treatment settings than the posted participant data represent. The safety counts apply to the three people in the dose-escalation combination cohort, not to every planned cohort or to a comparison of monotherapy with combination treatment. The listed secondary outcomes include measures of tumor response, disease control, and survival, but the registry record does not provide analysis entries for those outcomes.

In general, a safety endpoint in an early-phase study is used to describe adverse events observed during treatment and to characterize tolerability in the participants who were treated. Such descriptive observations can help frame further questions, but they do not by themselves establish whether an event was caused by a particular drug or whether one treatment is safer than another. Those questions require a suitable analysis and, for comparative claims, an appropriate comparison.

3. Trial Design

The registry describes NCT05374538 as a phase 1a/1b study of VIC-1911, an Aurora kinase A inhibitor, given alone and with sotorasib. It lists non-randomized allocation, no masking, and a single-group model. The study began on 2022-11-09, had a primary completion date of 2023-08-26, and is recorded as terminated. Enrollment is listed as 3.

The planned design included dose-escalation and expansion phases. Dose-escalation Cohort 1a was intended to evaluate VIC-1911 monotherapy in people whose locally advanced or metastatic disease was refractory to or had relapsed on prior KRAS G12C inhibitor therapy. Cohort 1b was intended to evaluate VIC-1911 with sotorasib in people with that treatment history or in people naive to KRAS G12C inhibitor therapy. The registry states that only Dose Level 1 of Cohort 1b opened and all 3 subjects received sotorasib.

The expansion phase included planned monotherapy and combination cohorts. The registry says that no subjects were treated in the Cohort 1a dose-escalation group and that the expansion phase did not open. The safety record lists zero participants at risk in each expansion group, as well as in the monotherapy dose-escalation group. The reported safety experience is therefore limited to the combination dose-escalation cohort.

Because allocation was non-randomized and there was no masking, the design does not provide a randomized, blinded comparison. In general, randomization helps balance participant characteristics across treatment groups, while masking can reduce some forms of assessment or reporting bias. Neither feature is described for this study. These design details do not invalidate the descriptive safety counts, but they limit what can be inferred by comparing groups or attributing observed events to a treatment.

The record does not report a rationale for the enrollment target, a detailed statistical analysis plan, or an explanation for termination. Those matters are not reported in the registry record, so the reason the study stopped and the extent to which the planned design was completed cannot be determined from the registry information.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: No subjects were treated in the Dose Escalation Phase, Cohort 1a. The Expansion Phase did not open.

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 baseline analysis population is the same for each group enrolled in the study. Subjects were enrolled only in Cohort 1b.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Treatment Emergent Adverse Events (Safety and Tolerability), measured over 9 months.

The primary endpoint is the incidence of treatment-emergent adverse events, with safety and tolerability assessed through adverse events and serious adverse events. Its unit is participants, and its timeframe is 9 months. The posted results report counts of participants with serious adverse events, participants with other adverse events, and deaths for each listed group.

In general, a participant-count endpoint records how many people experienced an event, rather than the total number of event episodes. A participant may experience more than one event, so event terms and participant counts answer different questions. The registry also lists serious adverse event terms and percentages; those terms provide descriptive detail, but do not establish causality or comparative risk.

A safety endpoint is used in early-phase research to document adverse experiences among those treated and to support a description of tolerability. It is important to read the endpoint alongside the population actually treated. For this study, the monotherapy dose-escalation cohort and expansion cohorts have no treated participants in the posted record; the available participant-level safety counts are in the combination dose-escalation cohort.

The registry does not describe a formal method for adjudicating events, attributing them to treatment, or handling participants with incomplete follow-up. Those methods are not reported in the registry record. Therefore, the endpoint supports a description of the posted counts, not a causal conclusion about VIC-1911, sotorasib, or their combination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a clinical endpoint is the outcome selected to answer a study question. This study’s primary endpoint is a participant count for treatment-emergent adverse events, with safety and tolerability assessed through adverse events and serious adverse events during a 9 months timeframe. A count records whether participants experienced an event; it is not the same as a count of every event episode. If one person experiences more than one event, the participant count and event count can differ.

What do the participant counts represent?

The posted results identify participants at risk and participants affected for serious adverse events and other adverse events. In general, a count is most interpretable when its population, observation period, and event definition are clear. Here, the endpoint specifies a 9 months timeframe, and the record describes the safety assessment as covering adverse events and serious adverse events. Details of event coding, follow-up completeness, and event adjudication are not reported in the registry record.

The distinction between a participant and an event matters when reading the serious adverse event terms. A list of terms describes the types of events recorded; it should not be treated as a count of unique people or as an estimate of treatment-attributable risk. The record’s listed terms—constipation, pneumonia, and embolism—each have a reported percentage of 33.3%. The registry does not provide enough detail to infer the relationship between each term, the number of episodes, and the participants affected beyond what it explicitly reports.

What does the design permit statistically?

In general, random allocation creates treatment groups that can be compared using a design intended to reduce systematic differences at baseline. This study is recorded as non-randomized, with a single-group model and no masking. Its planned cohorts are not a randomized control comparison, and the registry explicitly notes that the arms are not a like-for-like control comparison. Thus, differences between any listed groups would not automatically represent differences caused by treatment.

For this record, the practical limitation is more direct: the posted safety experience comes from the combination dose-escalation cohort, while the monotherapy dose-escalation and expansion groups have no treated participants. The registry says only Dose Level 1 opened in the combination cohort and all 3 subjects received sotorasib. There is no populated, concurrent monotherapy group against which to estimate a comparative safety effect. The counts should therefore be read as descriptive observations in the treated cohort.

Why does a small cohort affect precision?

In general, estimates based on few participants have substantial sampling uncertainty. A single participant’s experience can make a noticeable difference to a count or proportion, and the observed frequency may not closely represent the frequency in a larger population. Confidence intervals are one way to express uncertainty around estimates, but the registry record does not report confidence intervals for these safety results.

The small amount of observed safety information also limits the ability to examine whether events differ by prior treatment history, dose, or other participant characteristics. Those subgroup analyses and their results are not reported in the registry record. It would be inappropriate to infer that a zero count in a group with no treated participants represents a low event rate; there is no treated population in that group from which to estimate one.

What can be said about statistical testing?

The record lists 11 outcome measures and 0 analyses. It identifies secondary outcomes including objective response rate, duration of response, time to response, disease control rate, progression-free survival, and overall survival. The outcome list alone does not provide estimates, confidence intervals, hypothesis tests, or evidence of an observed treatment effect. No statistical analysis plan or inferential methods for the reported safety counts are described in the registry record.

In general, a hypothesis test evaluates how compatible observed data are with a specified null hypothesis under stated assumptions. A p-value is not a measure of effect size, clinical importance, or the probability that a treatment works. Without a reported analysis and its assumptions, no inferential conclusion should be attached to the counts in this record.

Multiplicity refers to the risk of false-positive findings when many outcomes or comparisons are tested. In general, researchers may address this through a prespecified testing hierarchy or an adjustment method. The registry lists multiple outcomes, but does not report a testing hierarchy or multiplicity adjustment. Since no analyses are recorded, there are no posted test results to interpret for multiplicity.

What is not available about analysis procedures?

The registry record does not report the analysis populations, missing-data procedures, or a detailed statistical plan. It does not specify how incomplete safety follow-up was handled or whether participants were analyzed according to a prespecified population definition. These omissions matter because such choices can affect the interpretation of estimates, especially when follow-up is incomplete or the treated population is small. They cannot be filled in by assuming standard practice; the appropriate conclusion is that these procedures are not reported in the registry record.

The record includes planning assumptions for sample-size illustrations based on an observed effect, but no observed effect or calculated sample-size results are reported in the registry record for this study. In general, a planning illustration asks how many participants might be needed under stated assumptions. It is not observed power and does not change the uncertainty of the outcomes already observed. No new sample-size estimate can be inferred from the posted safety counts.

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("Dose Escalation Phase, Cohort 1b: VIC-1911 Plus So")
n      <- c(3)
events <- c(3)
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  Dose Escalation Phase, Cohort 1b: VIC-1911 Plus So  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes: objective response rate, duration of response, time to response, disease control rate, progression-free survival, and overall survival. It also records 11 outcome measures and 0 analyses. The registry record does not report a prespecified testing hierarchy, a multiplicity adjustment, or statistical results for these secondary outcomes. The list of endpoints therefore indicates outcome areas named in the record, not findings or evidence that formal tests were conducted.

In general, testing many outcomes can increase the chance that at least one result appears statistically notable by chance. A prespecified hierarchy or an adjustment method can help address that issue, but neither is reported in the registry record. With no analysis entries, there are no reported p-values or confidence intervals to assess for multiplicity.

The registry also does not report missing-data procedures or define analysis populations. It is not reported how incomplete follow-up, withdrawals, or unavailable measurements were handled for safety or secondary outcomes. Those omissions are especially relevant when a study has very few treated participants, because the inclusion or exclusion of a participant can affect descriptive findings appreciably.

For the posted safety counts, the record provides participants at risk and participants affected in the listed groups. It does not state whether any participant had incomplete safety follow-up within the 9 months timeframe. The record also does not report an analysis population beyond its description of the relevant cohort. No missingness mechanism or imputation method should be assumed. The interpretation is consequently limited to the counts and descriptions the registry records.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: constipation (33.3%), pneumonia (33.3%), embolism (33.3%).

The serious adverse event figures are participant counts for the dose-escalation combination cohort. The registry reports 3 participants at risk and 2 affected. It also lists constipation, pneumonia, and embolism as top serious adverse event terms, each with 33.3%. These are descriptive entries; the record does not explain whether the events were considered related to VIC-1911, sotorasib, or both.

The deaths entry records 2 in the same cohort. The registry does not state in the information available whether those deaths were attributed to study treatment, nor does it provide timing or cause details. A death count should not be read as a treatment-related death count unless an attribution is reported. The record does not report that attribution.

The other adverse event figures show 3 participants at risk and 3 affected. This is a count of participants affected, not a count of all event episodes. The remaining groups list zero participants at risk and zero affected, consistent with the registry’s statements that no subjects were treated in the monotherapy dose-escalation cohort and that the expansion phase did not open. Those zero entries are not evidence of safety in untreated groups.

In general, adverse event counts describe events observed during a study and do not by themselves establish causality. Interpretation depends on event definitions, follow-up, clinical context, and how relatedness was assessed; these details are not reported in the registry record.

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

The posted results establish that the registry records safety events among participants in the dose-escalation combination cohort. They report 2 participants with serious adverse events, 3 with other adverse events, and 2 deaths in that group. The listed serious adverse event terms and their percentages add descriptive context. These observations are limited to the treated cohort and the information recorded for it.

They do not establish a comparative safety effect. The study was non-randomized, single-group, and unmasked, and the monotherapy and expansion groups have no treated participants. There is no randomized control group and no like-for-like comparison. Accordingly, the observed counts cannot show whether the combination caused an event, whether it changed event risk relative to another regimen, or whether another treatment would have produced different outcomes.

The results also do not establish efficacy. Although the registry names objective response rate, duration of response, time to response, disease control rate, progression-free survival, and overall survival as secondary outcomes, it records 0 analyses. No efficacy estimates are reported in the registry information. Outcome names should not be mistaken for outcome findings.

In general, a study’s observed event counts can support a description of what happened among participants who were treated. They do not necessarily predict what would happen in a broader population, particularly when the treated cohort is small. No confidence intervals are reported, and the registry does not give enough information to quantify the precision of the event estimates beyond the counts themselves.

The record also does not explain why the study was terminated or report whether the deaths or serious adverse events contributed to that decision. Without those details, neither the termination nor the event counts should be assigned a cause. The sound statistical interpretation is narrow: the registry documents these safety observations in the combination cohort, while comparative safety, treatment causality, and efficacy remain unestablished by the posted analyses.

14. Why This Trial Matters Statistically

This record matters statistically because its broad planned study description and its actual posted safety population differ. The study was designed to include VIC-1911 monotherapy and combination cohorts across dose-escalation and expansion phases, but the registry says no subjects were treated in the monotherapy dose-escalation cohort and the expansion phase did not open. Only Dose Level 1 in the combination cohort opened, and all 3 subjects received sotorasib. Reading the results in light of that distinction prevents planned cohorts from being mistaken for observed evidence.

The record also illustrates why design labels matter. A non-randomized, single-group study can describe the experience of treated participants, but it does not supply a randomized control comparison. With no treated monotherapy group, there is no basis in these results for comparing monotherapy with combination therapy. With no reported analyses, the listed secondary outcomes do not add evidence of response or survival effects.

Small safety cohorts can still provide useful descriptive information, but counts should not be overinterpreted. The record identifies serious adverse events, other adverse events, and deaths in the treated cohort. Those observations can focus attention on what was recorded, while leaving causality and comparative risk unresolved. The registry does not report event attribution, detailed follow-up procedures, or an inferential analysis.

In general, transparent reporting of the treated population, endpoints, and analytic methods is necessary for readers to judge both the scope and precision of clinical evidence. This record makes important constraints visible: a terminated study, a limited treated cohort, no randomized comparison, and no analysis entries. Those features define what the posted safety data can and cannot answer.

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 key trial-specific limitation is that the posted participant data do not cover the full set of planned cohorts. No subjects were treated in the VIC-1911 monotherapy dose-escalation cohort, and the expansion phase did not open. Only Dose Level 1 of the combination dose-escalation cohort opened, with all 3 subjects receiving sotorasib. The registry’s broad title and planned treatment groups should not be interpreted as evidence that each regimen or cohort was evaluated.

The study is non-randomized, unmasked, and recorded as a single-group model. The record explicitly notes that the arms are not a like-for-like control comparison. These features prevent a reliable treatment contrast from being drawn from the listed groups. The small treated cohort also constrains precision and limits meaningful assessment of variation across participant characteristics.

The registry records 0 analyses and does not report efficacy results for the listed secondary outcomes. It does not report an analysis plan, analysis populations, missing-data procedures, event attribution methods, or confidence intervals for the safety counts. The reason for termination is not reported in the registry record. These gaps limit assessment of the completeness and inferential meaning of the posted outcomes.

The safety data should also be interpreted as counts, not as proof of causality. The record lists serious adverse event terms and deaths, but does not provide the attribution or timing details needed to connect those events to a particular treatment. Zero entries in groups with no participants at risk are not evidence that those treatments caused no adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer — NCT05374538.
• Registry record last updated 2025-05-01; status last verified 2025-03.
• Results first posted 2025-05-01.
• 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

NCT05374538 is recorded as a terminated phase 1a/1b, non-randomized, unmasked, single-group study of VIC-1911 alone and with sotorasib for locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer. Enrollment is listed as 3. The recorded study dates are 2022-11-09 for start and 2023-08-26 for primary completion.

Only Dose Level 1 in the combination dose-escalation cohort opened, and all 3 subjects received sotorasib. No subjects were treated in the monotherapy dose-escalation cohort, and the expansion phase did not open. In the combination cohort, the registry records 2 participants with serious adverse events, 3 with other adverse events, and 2 deaths.

The registry lists six secondary outcome types, records 11 outcome measures, and records 0 analyses. It does not report comparative efficacy findings, a reason for termination, or the statistical and missing-data procedures needed for broader inference. The posted findings are descriptive safety counts from the treated combination cohort, not a randomized treatment comparison.