Testing Crizotinib as a Potential Targeted Treatment in Cancers With ROS1 Genetic Changes (MATCH-Subprotocol G): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing Crizotinib as a Potential Targeted Treatment in Cancers With ROS1 Genetic Changes (MATCH-Subprotocol G) (NCT04439253), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

3. Trial Design

This is a phase II, single-group treatment study within the MATCH program. Its official title identifies the population as patients with ROS1 translocations other than those with non-small cell lung cancer. The registry lists a total enrollment of 4. Allocation is recorded as not applicable, and masking is recorded as none. With no separate comparator group, the design can describe outcomes among treated participants but cannot make a randomized, concurrent comparison between crizotinib and another treatment.

Participants received crizotinib by mouth twice daily on days 1–28. Cycles were scheduled to repeat every 28 days in the absence of disease progression or unacceptable toxicity. The primary response endpoint was assessed using tumor evaluations beginning at baseline, then at the specified cycle intervals, continuing until disease progression, up to 3 years after registration. The record also lists 6-month progression-free survival rate and progression-free survival as secondary outcomes.

The primary endpoint population is described as patients who were eligible and received protocol treatment. The registry does not report a numerical ORR estimate or its confidence interval, and it lists 0 analyses. Consequently, the design and outcome definitions can be discussed, but the posted record does not support a numerical account of response or progression outcomes. The registry status is active, not recruiting. The registry record does not report a detailed rationale for the enrollment target or additional information about how the study's size was selected.

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: To be assigned to a specific MATCH subprotocol, patients needed to submit a tumor biopsy for molecular characterization and those with molecular variants addressed by treatments included in the trial entered corresponding MATCH subprotocol. For the subprotocol G, patients had to have an ROS1 translocations (other than patients with non-small cell lung cancer).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients who were eligible and received protocol 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.

Population: Eligible and treated patients

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration.

The primary endpoint is objective response rate, expressed as the percentage of eligible participants who received protocol treatment and whose best overall response was complete response or partial response. It summarizes whether a participant had a qualifying tumor response at any assessment used to determine the best overall response. The registry record says response was evaluated with RECIST version 1.1, the Cheson (2014) criteria for lymphoma, and the Response Assessment in Neuro-Oncology criteria for glioblastoma. It refers readers to the protocol for detailed response definitions.

As a general statistical concept, an objective response rate is a binary-outcome summary: each participant is classified according to whether the defined response occurred, and the result is expressed as a proportion or percentage. It can communicate the frequency of tumor shrinkage meeting prespecified criteria, but it does not by itself describe how long a response lasts, whether disease later progresses, or how outcomes compare with a control group. The registry lists progression-free survival outcomes separately.

The endpoint description specifies a two-sided binomial exact confidence interval at the 90% level. A confidence interval conveys uncertainty around an estimated response proportion; it does not remove uncertainty or establish a treatment effect against a comparator. The numerical estimate and interval are not reported in the registry record, so the endpoint's observed value and precision cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary endpoint: objective response, defined as a best overall response of complete response or partial response. General statistical explanation: for a binary endpoint, each participant is classified into one of two outcome categories for the analysis, and the response proportion is the number meeting the response definition relative to the endpoint population. Here, that population is specified as eligible participants who received protocol treatment. The registry does not report the numerical response count or proportion.

Why use a confidence interval?

The endpoint description specifies a two-sided binomial exact confidence interval at the 90% level. In general, a confidence interval expresses the uncertainty associated with an estimate. It gives a range of values compatible with the observed data under the stated method and its assumptions. It is not a guarantee that the true value lies within that particular interval, and it does not answer a causal question by itself. The registry record does not report the interval's endpoints, so its width and the precision of the response estimate cannot be evaluated.

An exact binomial interval is designed for a proportion derived from binary outcomes. It is distinct from an interval based on a large-sample normal approximation. The method matters especially when the amount of information is limited, because approximate methods can behave poorly with sparse data. General explanation does not establish the interval's actual width in this trial: that requires the unreported response result.

How were responses assessed?

The registry describes assessments at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years after registration. The best overall response was evaluated using different criteria according to disease type: RECIST version 1.1, Cheson (2014) criteria for lymphoma, and Response Assessment in Neuro-Oncology criteria for glioblastoma. These criteria provide structured rules for classifying tumor response. The registry directs readers to the protocol for detailed definitions, which are not reproduced in the record.

Using a best overall response endpoint means the analysis is based on the participant's best qualifying response across assessments, rather than on a single measurement alone. That classification depends on the assessment schedule and the criteria applied. The registry description does not report how many assessments each participant completed, whether assessments were independently reviewed, or how missing or unevaluable assessments were handled.

What does the single-group design allow?

The study is recorded as single-group, with allocation not applicable and no masking. In general, a single-group study can estimate outcomes observed among people treated under the study conditions. It does not provide a concurrent comparison that separates treatment effects from other explanations for those outcomes. Random allocation to distinct groups is not part of the design described in this record. Therefore, even if numerical response results were available, the design would not support the same direct comparative interpretation as a randomized trial.

The registry lists enrollment of 4. That is an enrollment description, not a justification of statistical adequacy. A sample-size justification, including any target effect or precision goal, is not reported in the registry record. The record also does not describe interim analyses or a detailed statistical analysis plan.

How should planning calculations be read?

General explanation: sample-size planning calculations explore how many participants might be needed under specified assumptions about an effect, significance level, allocation, and statistical method. They are planning illustrations, not evidence about the trial's observed treatment effect and not observed power. The assumptions described for the planning illustration include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. Those are planning assumptions and do not describe the single-group study's actual allocation.

The posted planning description distinguishes between time-to-event calculations, which refer to total events, and other calculations, which refer to participants per arm. No numerical planning results are reported in the registry record. In addition, a randomized two-arm planning framework should not be mistaken for the design of this single-group trial. Such illustrations cannot supply a missing ORR estimate, confidence interval, or comparison.

What remains unavailable?

The registry record lists 0 analyses and does not provide numerical primary or secondary outcome results. It also does not report details of endpoint-level missing data, analysis populations beyond the primary endpoint population description, or the handling of incomplete follow-up. These omissions limit assessment of the analysis beyond what can be learned from the stated endpoint definition and assessment schedule. No estimate should be reconstructed from enrollment or safety entries, because those figures do not establish the missing efficacy outcomes.

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("Treatment (Crizotinib)")
n      <- c(4)
events <- c(1)
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  Treatment (Crizotinib)  4  1  25.0  0.6  80.6  4.6  69.9  5.3  71.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists objective response rate as the primary outcome and 6-month progression-free survival rate and progression-free survival as secondary outcomes. It does not report a multiplicity procedure, such as an adjustment to account for testing several outcomes. The analysis plan for controlling the chance of false-positive findings across outcomes is therefore not reported in the registry record. Because numerical outcome analyses are also absent, there are no reported results with which to assess how multiplicity may have affected interpretation.

Missing-data methods are not reported in the registry record. The endpoint population is described as participants who were eligible and received protocol treatment, but the record does not explain how participants without an evaluable tumor assessment, who discontinue treatment, or whose follow-up ends early were handled for the primary endpoint. Nor does it report how incomplete observations were handled for the progression-free survival outcomes. The assessment schedule alone does not establish that all scheduled measurements were obtained.

The registry does not provide a detailed account of analysis populations for the secondary outcomes or specify whether analyses included all enrolled participants, only treated participants, or another group. The primary endpoint description does identify eligible and treated patients, but that description does not resolve the handling of individual exclusions or unevaluable outcomes.

These are reporting limitations, not evidence that a particular procedure was or was not used in the conduct of the study. Without the analysis plan and numerical results, readers cannot assess the consequences of multiplicity, missing outcome data, or population choices. The record lists 0 analyses, so those details cannot be inferred from posted outcome analyses.

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 (25.0%), lymphocyte count decreased (25.0%), acute kidney injury (25.0%).

The registry safety entry lists 4 participants at risk for serious adverse events, with 2 affected. For other adverse events, it lists 4 at risk and 3 affected. It also lists 4 deaths. The record names abdominal pain, lymphocyte count decreased, and acute kidney injury among the top serious adverse event terms, each recorded at 25.0%.

These figures are descriptive registry entries. The record does not state that the listed serious events or deaths were caused by crizotinib, nor does it provide the event timing, duration, severity details beyond the serious-event classification, or individual circumstances needed to assess attribution. A listed death should not automatically be interpreted as a treatment-related death. Likewise, a term's percentage does not establish its cause or clinical course.

The safety figures should also be kept distinct from the efficacy endpoint. They do not establish how many participants had an objective response, and the record does not report numerical response results. The limited safety counts describe the entries in this registry record; they do not by themselves provide a comparative assessment of risks because the trial has no control group.

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

The record establishes that this was a phase II MATCH subprotocol studying crizotinib in patients with ROS1 translocations other than non-small cell lung cancer. It specifies a single-group design, the treatment schedule, the primary response definition, and the methods named for tumor assessment and confidence-interval calculation. It also records enrollment of 4 and includes descriptive safety entries.

What the record does not establish is the numerical objective response rate. The primary endpoint result and its confidence interval are not reported in the registry record. Numerical results for the secondary progression-free survival outcomes are also not reported. Without these results, the posted record cannot show the observed frequency of response, the precision of an estimate, or the progression outcomes. The study's stated purpose and endpoint are not themselves evidence of a particular result.

Even if outcome estimates were available, the single-group design would not provide a randomized comparison with another treatment or a control condition. A response observed in a treated group would be an outcome description; it would not, on its own, identify what would have happened to comparable participants under a different treatment. The registry record also does not provide participant-level clinical details or a full analysis plan that could address such questions.

The adverse event entries show that serious and other events were recorded, along with deaths, but the record does not establish that these were caused by treatment. Their interpretation is limited by the lack of a comparison group and by the absence of reported timing and attribution details. These limitations apply to the available record and should not be mistaken for evidence that an outcome was absent.

In short, the registry describes the question the study set out to examine and how response was to be assessed. It does not report the primary or secondary numerical outcome analyses needed to judge the observed efficacy results or their precision. No conclusion about treatment benefit or lack of benefit follows from these missing results.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks a focused response question in a defined molecular subgroup: patients with ROS1 translocations, excluding those with non-small cell lung cancer. The registry's disease-specific response criteria recognize that tumor assessment can require different classification frameworks for different cancer types. The primary endpoint brings those assessments together as a binary response outcome, defined by complete or partial response.

The design also illustrates the distinction between estimating an outcome and comparing treatments. A single-group phase II study can be structured to describe response among treated participants, but without a concurrent randomized comparator it cannot directly estimate a treatment contrast. This matters when interpreting any response proportion: the statistical summary and the causal question are not the same.

Precision is especially important in a study with enrollment of 4. The registry specifies an exact 90% confidence interval for the primary response proportion, which is a way to communicate uncertainty around a binary-outcome estimate. However, the estimate and interval are not reported in the registry record. The statistical method can be identified, but its practical implication for this study cannot be assessed without the result.

The record also separates the primary response endpoint from progression-free survival outcomes and reports safety entries separately. These outcomes answer different questions and should not be treated as substitutes for one another. Since the numerical efficacy analyses are not reported, the statistical importance of this trial in the available registry record lies chiefly in its defined population, design, endpoint, and the limits those features place on interpretation—not in an unreported efficacy conclusion.

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 consequential limitation of the registry record is that it does not report numerical results for the primary objective response rate or its specified confidence interval. It also does not report numerical results for the listed progression-free survival outcomes. As a result, the observed efficacy findings and their precision cannot be assessed from the record.

The single-group design has no concurrent comparator, and allocation is recorded as not applicable. This limits the ability to distinguish outcomes associated with treatment from outcomes that might occur for other reasons. The record also states that masking was none. It does not provide further information about response review procedures or whether assessments were independently reviewed.

Enrollment is recorded as 4, but a sample-size justification is not reported in the registry record. The record lists planning assumptions for illustrative calculations, but these do not provide evidence about observed power and do not replace the missing outcome analyses. A detailed statistical analysis plan and interim-analysis information are not reported in the registry record.

Other limitations include the absence of reported methods for missing data, endpoint-specific analysis populations beyond the primary population description, and details of follow-up completeness. The response assessments were scheduled through up to 3 years after registration, but the record does not establish how much follow-up was available for each participant. Safety figures are also limited by the lack of reported event attribution, timing, and a comparison group. These are limitations of the information available in the registry record; they do not establish that the underlying study lacked procedures or data that are not reported there.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing Crizotinib as a Potential Targeted Treatment in Cancers With ROS1 Genetic Changes (MATCH-Subprotocol G) — NCT04439253.
• Registry record last updated 2026-09-18; status last verified 2026-09.
• Results first posted 2022-09-28.
• 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

NCT04439253 is a phase II, single-group MATCH treatment subprotocol evaluating crizotinib in patients with ROS1 translocations other than non-small cell lung cancer. The registry lists enrollment of 4, no masking, and allocation as not applicable. Crizotinib was scheduled by mouth twice daily on days 1–28, with 28-day cycles continuing in the absence of progression or unacceptable toxicity.

The primary endpoint is objective response rate among eligible participants who received protocol treatment, using complete or partial response as the response definition. The registry describes disease-specific response criteria and a two-sided binomial exact 90% confidence interval. It lists progression-free survival outcomes as secondary endpoints.

Numerical primary and secondary outcome results are not reported in the registry record, which lists 0 analyses. Safety entries include serious and other adverse events and deaths, without reported attribution details. The registry status is active, not recruiting.