This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation. (NCT05445843), a non-randomized phase 2 study. The primary outcome is Overall Response Rate (ORR) as Determined by the Investigator in Cohort A.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05445843 |
| Phase | Phase 2 |
| Condition | Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 95 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with locally advanced or metastatic non-small cell lung cancer whose tumors have a KRAS G12C mutation. Cohort A includes tumors with PD-L1 expression < 1%, regardless of STK11 mutation status. Cohort B includes tumors with PD-L1 expression ≥ 1% and an STK11 co-mutation.
Intervention
JDQ443 given as a single-agent first-line treatment. The registry record identifies JDQ443 as the study drug and describes the study as evaluating its antitumor activity and safety in the two specified patient groups.
Comparator
There is no separate control treatment described. The study is non-randomized and open-label, with parallel cohorts defined by tumor characteristics. Those cohorts are not like-for-like control groups, so their results should not be treated as a randomized treatment comparison.
Primary question
In Cohort A, what percentage of participants has a confirmed complete or partial response as best overall response, according to the investigator and RECIST 1.1? Overall response rate in Cohort B is listed as a key secondary outcome, not the primary outcome.
The clinical question is about observed tumor response and safety in selected groups receiving JDQ443, rather than whether JDQ443 outperforms another treatment. The cohort definitions matter: Cohort A is based on PD-L1 expression < 1% and permits either STK11 status, while Cohort B requires both PD-L1 expression ≥ 1% and an STK11 co-mutation. The distinct eligibility criteria mean that differences between cohort outcomes could reflect differences in the populations as well as treatment response. The registry record does not report a numerical primary-outcome result, so the magnitude and precision of the response estimate cannot be assessed from the record.
3. Trial Design
KontRASt-06 is listed as an open-label Phase II trial of JDQ443 single-agent treatment. Its allocation is non-randomized, its masking is none, and its model is parallel. Participants are grouped into Cohort A or Cohort B by tumor biomarkers; the registry does not describe a separate control arm. Because allocation is not randomized and the cohorts have different defining characteristics, this design does not support treating the cohorts as comparable treatment arms.
The registry lists enrollment of 95. Cohort A is for participants with KRAS G12C-mutated tumors and PD-L1 expression < 1%, regardless of STK11 mutation status. Cohort B is for participants with KRAS G12C-mutated tumors, PD-L1 expression ≥ 1%, and an STK11 co-mutation. The primary outcome is investigator-assessed overall response rate in Cohort A; investigator-assessed overall response rate in Cohort B is a key secondary outcome. Other listed secondary outcomes concern adverse events and plasma JDQ443 concentrations.
The study start date is 2022-12-06, and the primary completion date is 2024-11-04. The registry status is active, not recruiting. These record details describe the study's administrative status and planned outcome timeframe; they do not establish that follow-up is complete or that results are available. The primary outcome timeframe is up to approximately 22 months.
The registry identifies Novartis Pharmaceuticals as sponsor. Details such as the intended allocation between cohorts, treatment administration schedule, follow-up procedures, and site-level conduct are not reported in the registry record. No randomized comparison or masking should be inferred from the parallel-cohort structure.
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
| Stage | Cohort A- PD-L1<1% | Cohort B- PD-L1≥ 1% and STK11 Mutation |
|---|---|---|
| STARTED | 72 | 23 |
| Pharmacokinetic Analysis Set (PAS) | 69 | 23 |
| Full Pharmacokinetic Analysis Set (FPAS) | 14 | 9 |
| Treatment ongoing | 25 | 5 |
| Discontinued from treatment and continued in the follow-up period | 32 | 10 |
| Discontinued from treatment and did not enter the follow-up period | 15 | 8 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 72 | 23 |
Reasons for not completing this period:
| Reason | Cohort A- PD-L1<1% | Cohort B- PD-L1≥ 1% and STK11 Mutation |
|---|---|---|
| Treatment ongoing at the time of the data cut-off date 04NOV2024 | 25 | 5 |
| Progressive disease | 17 | 9 |
| Physician Decision | 16 | 4 |
| Death | 6 | 3 |
| Subject decision | 6 | 2 |
| Adverse Event | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) comprised all participants to whom study treatment had been assigned and who received at least one dose of study treatment.
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.
| Characteristic | Unit | Cohort A- PD-L1<1% | Cohort B- PD-L1≥ 1% and STK11 Mutation | Total |
|---|---|---|---|---|
| Participants analysed | 72 | 23 | 95 | |
| Age, Continuous | Years | 67.7 (SD 7.68) | 63.7 (SD 10.29) | 66.7 (SD 8.50) |
| Sex: Female, Male: Female | Participants | 25 | 5 | 30 |
| Sex: Female, Male: Male | Participants | 47 | 18 | 65 |
| Race/Ethnicity, Customized: White | Participants | 57 | 13 | 70 |
| Race/Ethnicity, Customized: Asian | Participants | 11 | 7 | 18 |
| Race/Ethnicity, Customized: Unknown | Participants | 4 | 3 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate (ORR) as Determined by the Investigator in Cohort A, measured over Up to approximately 22 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage (%) of participants |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is overall response rate in Cohort A, expressed as the percentage of participants whose best overall response is a confirmed complete response or partial response. The response determination is made by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The outcome timeframe is up to approximately 22 months.
In general, overall response rate is a measure of the proportion of participants who meet specified criteria for tumor shrinkage. Requiring confirmation means that a response must be confirmed according to the endpoint definition, rather than counted solely on the basis of an initial assessment. The endpoint therefore represents a defined response category; it is not, by itself, a measure of how long a response lasts, time until disease progression, or overall survival.
The registry defines the Full Analysis Set as all participants to whom study treatment had been assigned and who received at least one dose of study treatment. This is the stated population for the primary outcome. The registry record does not report the number of participants in that analysis, the number with confirmed responses, the estimated response percentage, or its confidence interval. Without those results, the endpoint definition can be described, but the observed response rate and its precision cannot be interpreted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study designed to evaluate antitumor activity and safety of JDQ443 in two biomarker-defined groups. The primary efficacy outcome is overall response rate in Cohort A, and the record specifies how a response is defined. However, it does not report a numerical result for this outcome. There is therefore no registry-reported response percentage or confidence interval to interpret, and no basis in this record for describing the magnitude or precision of the primary outcome.
The distinction between the cohorts is central to interpretation. Cohort A includes KRAS G12C-mutated tumors with PD-L1 expression < 1%, regardless of STK11 mutation status. Cohort B requires PD-L1 expression ≥ 1% and an STK11 co-mutation. The registry lists overall response rate in Cohort B as a key secondary outcome. Since assignment is non-randomized and cohort membership depends on tumor characteristics, a difference between their response estimates would not be an unbiased estimate of a treatment effect between comparable groups. The cohorts are not a like-for-like control comparison.
In general, a confidence interval conveys uncertainty around an estimate: a narrower interval indicates greater precision, while a wider interval indicates less precision. The primary outcome is specified with a 95% confidence interval, but the numerical interval is not reported in the registry record. Consequently, the uncertainty around the primary response estimate is also not assessable from the record. No p-value or inferential comparison for the primary outcome is reported.
The registry lists safety outcomes, including serious adverse events, other adverse events, and deaths, with counts for each cohort. These counts describe events recorded among participants at risk, but do not establish that JDQ443 caused each event. The record also lists several serious adverse-event terms with percentages. Interpretation of those percentages depends on the denominator and event definitions; cohort-specific rates should not be inferred where the record does not identify them.
The posted results do not report efficacy estimates, analysis populations beyond the stated Full Analysis Set definition, or a comparison against another treatment. The study's single-arm treatment within biomarker-defined cohorts can provide descriptive evidence about outcomes in those participants, but the design alone cannot separate treatment-associated outcomes from other influences. The results should be read as study-specific observations, not as a controlled estimate of comparative benefit.
9. Statistical Methods Explained
The primary outcome is a proportion: the count of participants meeting the response definition considered in relation to the analysis population. The registry states that response means a confirmed complete response or partial response as best overall response, assessed by the investigator according to RECIST 1.1. The registry also specifies the Full Analysis Set as participants to whom study treatment had been assigned and who received at least one dose. It does not report the event count or the denominator used for the primary estimate, so neither can be reconstructed from the record.
What does the confidence interval describe?
In general, a confidence interval describes the uncertainty associated with an estimate under the statistical method used. It is not a guarantee that the true value lies within a particular interval, and it does not express the probability that the treatment is effective. For a response proportion, the interval helps readers judge how precisely the observed proportion estimates the underlying response rate in a relevant population. The registry specifies a 95% confidence interval for the primary outcome, but its numerical limits are not reported in the registry record. The interval's width and the estimate's precision therefore cannot be evaluated.
What does the non-randomized structure imply?
In general, random allocation helps balance measured and unmeasured participant characteristics across treatment groups. This study is non-randomized and has no separate comparator treatment in the registry description. Its parallel cohorts are defined by different biomarker criteria, not by random assignment to alternative treatments. A comparison of cohort response rates would therefore be descriptive; it would not isolate a treatment effect from differences in cohort composition. Open-label status also means treatment is not masked. The primary endpoint is investigator determined, and the registry does not report whether response was independently reviewed.
How should the sample-size illustrations be read?
In general, a sample-size calculation asks how many observations would be needed to detect a specified effect under stated statistical assumptions. The planning illustrations associated with this record are explicitly not the trial's own design. Their assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations refer to total events using the Schoenfeld method; for other outcomes, they refer to participants per arm. They are planning scenarios, not evidence about the study's achieved power or observed result. In particular, sample-size illustrations do not turn the non-randomized cohorts into a randomized comparison. The registry record does not report the trial's own sample-size justification.
What can be inferred from event counts?
In general, adverse-event summaries count events or participants meeting specified event criteria within a defined observation period. A count alone does not describe severity beyond the classification used, duration, recurrence, timing, or causal attribution. The registry lists CTCAE-assessed adverse-event outcomes, but the specific assessment details and additional analyses are not reported in the registry record. The serious-event counts and other event counts should not be conflated: they are separately listed outcomes, and the same participant might contribute to more than one type of event summary. The record does not provide enough detail to infer overlap or to calculate a participant-level risk from those summaries.
The registry record lists 0 analyses. This means no outcome analysis entries are reported in the record; it does not supply the missing primary estimate or statistical details. The record does not report the model or interval method used for the primary confidence interval, any covariate adjustment, handling of censoring, or sensitivity analyses. Such details should not be inferred from general conventions for Phase II trials.
10. Multiplicity, Missing Data and Analysis Populations
The study lists multiple outcomes: the primary response measure in Cohort A, a key secondary response measure in Cohort B, safety outcomes, and pharmacokinetic measures. When many outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. Statistical procedures for addressing that issue, such as a prespecified testing hierarchy or adjustment, are not reported in the registry record. The record also does not report interim analyses or stopping rules.
Missing-data handling is not reported in the registry record. The endpoint definition identifies the Full Analysis Set as participants assigned study treatment who received at least one dose, but it does not explain how participants without an evaluable response assessment are treated, how missing assessments affect best overall response, or whether any sensitivity analyses are planned. The number included in the primary analysis is not reported.
The registry does not report a statistical analysis plan, the method used to calculate the primary confidence interval, or any adjustment for baseline characteristics. It lists 0 analyses, so numerical outcome analyses and their methods are not available in the record. It is also not reported whether the primary analysis is intended to be descriptive or to test a formal hypothesis. These omissions limit assessment of multiplicity, missingness, and the prespecification of analysis choices.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Cohort A- PD-L1<1% | 29 | 72 | 40.3% |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 10 | 23 | 43.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort A- PD-L1<1% | 15 of 72 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 4 of 23 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort A- PD-L1<1% | 60 of 72 |
| Cohort B- PD-L1≥ 1% and STK11 Mutation | 21 of 23 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort A- PD-L1<1% | Cohort B- PD-L1≥ 1% and STK11 Mutation |
|---|---|---|---|
| Pneumonia | Infections and infestations | 5 of 72 | 2 of 23 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 5 of 72 | 2 of 23 |
| Anaemia | Blood and lymphatic system disorders | 3 of 72 | 0 of 23 |
| Pericardial effusion | Cardiac disorders | 2 of 72 | 1 of 23 |
| Sepsis | Infections and infestations | 1 of 72 | 2 of 23 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 3 of 72 | 0 of 23 |
| Embolism | Vascular disorders | 1 of 72 | 1 of 23 |
| Abdominal pain | Gastrointestinal disorders | 1 of 72 | 0 of 23 |
| Diarrhoea | Gastrointestinal disorders | 0 of 72 | 1 of 23 |
| Intestinal ischaemia | Gastrointestinal disorders | 1 of 72 | 0 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort A- PD-L1<1% | Cohort B- PD-L1≥ 1% and STK11 Mutation |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 21 of 72 | 4 of 23 |
| Nausea | Gastrointestinal disorders | 18 of 72 | 5 of 23 |
| Diarrhoea | Gastrointestinal disorders | 19 of 72 | 1 of 23 |
| Constipation | Gastrointestinal disorders | 12 of 72 | 6 of 23 |
| Oedema peripheral | General disorders and administration site conditions | 13 of 72 | 5 of 23 |
| Asthenia | General disorders and administration site conditions | 14 of 72 | 3 of 23 |
| Fatigue | General disorders and administration site conditions | 13 of 72 | 4 of 23 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 14 of 72 | 2 of 23 |
| Decreased appetite | Metabolism and nutrition disorders | 11 of 72 | 4 of 23 |
| Weight decreased | Investigations | 8 of 72 | 5 of 23 |
Serious events with the highest arm-level rate: pneumonia (8.7%), sepsis (8.7%), dyspnoea (8.7%), pericardial effusion (4.3%), diarrhoea (4.3%).
The registry lists serious adverse-event counts by cohort. In Cohort A, 72 participants were at risk for serious adverse events and 29 were affected; 72 were at risk for other adverse events and 60 were affected, with 15 deaths listed. In Cohort B, 23 participants were at risk for serious adverse events and 10 were affected; 23 were at risk for other adverse events and 21 were affected, with 4 deaths listed. These are separate summaries, not a comparison of randomized groups.
The record lists pneumonia, sepsis, and dyspnoea at 8.7% each among the top serious adverse-event terms. Pericardial effusion, diarrhoea, and pyrexia are each listed at 4.3%. The registry information does not establish from these percentages alone whether the terms are cohort-specific, nor does a listed event establish treatment causality. Serious adverse events, other adverse events, and deaths are different summaries and should not be treated as interchangeable. The registry does not report further context about timing, duration, recurrence, or attribution for these figures.
12. What the Result Does, and Does Not, Mean
The record defines a study of single-agent JDQ443 in first-line treatment for locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer. It identifies two biomarker-defined cohorts and specifies investigator-assessed overall response rate in Cohort A as the primary outcome. These details establish what the study set out to evaluate and how its primary response endpoint is defined.
The record does not report a numerical primary response result or confidence interval. It therefore does not show the observed response rate or how precisely that rate was estimated. Although safety counts are listed, those counts alone do not establish whether an event was caused by treatment, and they do not provide a comparison against another treatment.
The non-randomized design is important: Cohort A and Cohort B differ in their eligibility criteria, and neither is described as a control arm. Results from one cohort cannot be treated as a causal comparison with the other. More generally, an observed response proportion in a single treatment group does not by itself establish what would have happened to similar participants under an alternative treatment.
The findings represented in the registry should be understood as descriptions of a Phase II study and its listed outcomes, not as a comparative treatment estimate. The registry status is active, not recruiting, and the listed primary completion date is 2024-11-04; these administrative entries do not substitute for reported outcome data. The registry record does not report a numerical efficacy analysis, a comparison with standard care, or enough detail to determine how missing outcome assessments were handled.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way it separates participants by tumor biomarkers while assessing a single-agent treatment. The primary efficacy question concerns Cohort A, defined by PD-L1 expression < 1%, whereas Cohort B requires PD-L1 expression ≥ 1% and an STK11 co-mutation. Keeping those definitions explicit is essential when reading outcome estimates: the cohorts represent different clinical and biological groups, not interchangeable arms of a randomized experiment.
The design also illustrates the difference between measuring an outcome and estimating a comparative treatment effect. Investigator-assessed overall response rate is a clear, defined endpoint, but an estimate from a non-randomized cohort remains descriptive unless supported by a suitable comparison and appropriate assumptions. The registry record does not supply a numerical primary estimate, so its precision and observed magnitude cannot be judged.
Finally, the record lists both efficacy and safety outcomes, while the available registry information leaves important analysis details unreported. Distinguishing event counts from causal conclusions, and planning illustrations from observed trial results, is necessary for a calibrated statistical reading. The study's value as evidence depends not only on its endpoint definitions and enrollment but also on transparent reporting of estimates, uncertainty, analysis populations, and methods.
14. 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, a confidence interval, or a response count for Cohort A. It therefore does not permit assessment of the observed response magnitude or precision. A key secondary response outcome is listed for Cohort B, but its numerical result is also not reported in the registry record.
The study is open-label and non-randomized. There is no separate control treatment described, and the cohorts have different eligibility criteria. This limits direct interpretation of between-cohort differences and means the design does not provide a randomized estimate of comparative treatment effects. The primary endpoint is investigator determined; whether independent review was performed is not reported in the registry record.
Further limitations arise from missing analysis details. The record does not report the primary confidence-interval method, the handling of missing or unevaluable assessments, planned interim analyses, multiplicity procedures, or the trial's sample-size justification. It lists 0 analyses. The listed enrollment does not by itself establish the number included in the primary analysis or the number with evaluable follow-up. These gaps restrict evaluation of the analysis and its uncertainty.
The safety summaries report counts and selected event percentages, but additional context on causality, timing, duration, recurrence, and cohort-specific denominators for the listed serious-event terms is not reported in the registry record. As a result, the event summaries should be read descriptively and not as proof that the study drug caused each event.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation. — NCT05445843.
- Registry record last updated 2026-10-08; status last verified 2026-09.
- Results first posted 2025-10-09.
- 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.
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18. Record Summary
KontRASt-06 (NCT05445843) is an open-label, non-randomized Phase II trial of single-agent JDQ443 in locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer. Cohort A includes tumors with PD-L1 expression < 1%, regardless of STK11 mutation status; Cohort B requires PD-L1 expression ≥ 1% and an STK11 co-mutation. The registry lists enrollment of 95 and Novartis Pharmaceuticals as sponsor.
The primary outcome is investigator-assessed overall response rate in Cohort A, defined as confirmed complete or partial response by RECIST 1.1. Overall response rate in Cohort B is a key secondary outcome. The registry record does not report a numerical primary efficacy result or confidence interval. It lists safety counts by cohort and selected serious adverse-event terms, but these data do not establish causality or provide a randomized comparison. The record status is active, not recruiting.