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 Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer (NCT04941287), a randomized phase 2 study. The primary outcome is Number of Participants Experiencing a Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04941287 |
| Phase | Phase 2 |
| Condition | Metastatic Distal Bile Duct Adenocarcinoma, Metastatic Gallbladder Carcinoma, Metastatic Intrahepatic Cholangiocarcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 57 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with previously treated, unresectable biliary tract cancers. The registry lists cancers of the distal bile duct, gallbladder, and intrahepatic bile ducts, including metastatic, recurrent, and stage IV conditions.
Intervention
Atezolizumab and varlilumab, with cobimetinib added to the combination in one study arm. These are the treatments being evaluated in the trial; the registry record does not establish what their effects are.
Comparator
Atezolizumab and varlilumab without cobimetinib. Comparing the two arms addresses the added-treatment question within this trial, rather than comparing either regimen with no treatment or another standard regimen.
Primary question
How many participants experience a complete or partial response after receiving at least one dose of their assigned regimen? The trial’s stated response definition uses RECIST v1.1. The registry record does not report the response counts for either arm or an arm-to-arm analysis.
The central comparison is whether the observed response experience differs between the combination that includes cobimetinib and the combination without it. Because assignment was randomized, the design is intended to compare groups formed through allocation rather than through participants’ treatment choices. Randomization alone, however, does not supply an estimate of the treatment contrast or its precision. Those require outcome results and an appropriate analysis, which are not reported in the registry record.
The question is specific to the enrolled population and the response outcome. It is not, by itself, a question about overall survival, quality of life, or whether either regimen is better than an alternative not studied in these arms. The registry lists overall survival and other outcomes among secondary outcomes, but it does not report their results in the record.
3. Trial Design
This is a randomized, parallel-group phase 2 study with an enrollment of 57 participants. The registry identifies the study as unmasked, meaning masking is not listed. Participants are assigned to one of two regimens: Arm A combines cobimetinib, atezolizumab, and varlilumab; Arm B combines atezolizumab and varlilumab without cobimetinib. The intended contrast is therefore the addition of cobimetinib to the two-drug combination.
The study concerns previously treated, unresectable biliary tract cancers. The listed conditions include metastatic, recurrent, and stage IV cancers of the distal bile duct, gallbladder, and intrahepatic bile ducts, as well as unresectable liver carcinoma. The registry’s brief summary describes the trial as evaluating these regimens in people whose biliary tract cancer cannot be removed by surgery.
The listed primary outcome is the number of participants experiencing a response, with response defined using RECIST v1.1. Its timeframe is up to 2 years. Secondary outcomes listed include grade 3, 4 and 5 adverse events, overall survival, changes in T-cell populations and clearance rates, and anti-drug antibodies.
The registry lists the National Cancer Institute as sponsor, a start date of 2021-12-15, and a primary completion date of 2024-01-02. Its current status is active, not recruiting. That status does not establish that all follow-up is complete or that all results have been reported. The registry record does not report the protocol’s sample-size justification, detailed statistical analysis plan, or planned interim analyses. The arm descriptions are incomplete in the record, so further treatment or assessment details cannot be established from them.
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 | Arm A (Cobimetinib, Atezolizumab, Varlilumab) | Arm B (Atezolizumab, Varlilumab) |
|---|---|---|
| STARTED | 29 | 28 |
| COMPLETED | 26 | 27 |
| NOT COMPLETED | 3 | 1 |
Reasons for not completing this period:
| Reason | Arm A (Cobimetinib, Atezolizumab, Varlilumab) | Arm B (Atezolizumab, Varlilumab) |
|---|---|---|
| Rapid decline before starting treatment | 3 | 1 |
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 | Arm A (Cobimetinib, Atezolizumab, Varlilumab) | Arm B (Atezolizumab, Varlilumab) | Total |
|---|---|---|---|---|
| Participants analysed | 29 | 28 | 57 | |
| Age, Continuous | Years | 63 (32 to 77) | 67 (33 to 85) | 64 (32 to 85) |
| Sex: Female, Male: Female | Participants | 17 | 19 | 36 |
| Sex: Female, Male: Male | Participants | 12 | 9 | 21 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 5 | 8 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 24 | 22 | 46 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 3 | 2 | 5 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): White | Participants | 18 | 23 | 41 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 6 | 2 | 8 |
| Region of Enrollment: United States | participants | 29 | 28 | 57 |
| Subgroup: Gallbladder cancer | Participants | 6 | 5 | 11 |
| Subgroup: Intrahepatic cholangiocarcinoma | Participants | 21 | 17 | 38 |
| Subgroup: Extrahepatic cholangiocarcinoma | Participants | 2 | 6 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Experiencing a Response, measured over Up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who experience a complete response or a partial response after receiving at least one dose of the assigned study regimen. The registry defines complete response as disappearance of all lesions and partial response as at least 30% decrease in the sum of target lesions, assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The stated assessment timeframe is up to 2 years.
This is a binary participant-level outcome for the purpose of the count: a participant either meets the response definition or does not. In general, tumor-response endpoints are used to describe whether measurable tumors meet prespecified criteria for shrinkage or disappearance. Applying standard criteria can make the definition more consistent than an informal judgment of improvement. The count can then be compared between randomized groups if arm-level results and an analysis are available.
A response count does not, on its own, describe how long a response lasts, whether symptoms change, or how long participants live. Those questions require other outcomes and their corresponding results. Although overall survival is listed as a secondary outcome, its results are not reported in the registry record. The primary response counts, group denominators for that outcome, and an inferential comparison are also not reported in the registry record, so the endpoint’s observed magnitude and precision cannot be assessed from the listed information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the trial design and endpoint but does not report the arm-level results for the primary response outcome. It also lists no analysis records. As a result, the response experience in Arm A cannot be compared with that in Arm B from the record, and no estimate of the size or precision of a response difference can be stated. The missing result is not evidence that the regimens had the same response experience; it means that the relevant comparison is not reported in the registry record.
The record does report safety counts. For serious adverse events, it lists 24 affected participants among 29 at risk in Arm A and 25 among 28 at risk in Arm B. For other adverse events, it lists 25 among 29 in Arm A and 27 among 28 in Arm B. These are descriptive counts, not an adjusted comparison. The record also lists deaths for the groups: 21 in Arm A and 23 in Arm B. Those figures should not be interpreted as evidence that a treatment caused or prevented a death; the registry entry does not provide a causal analysis or the context needed to interpret the death counts as a treatment effect.
The listed serious-event terms include disease progression at 57.1%, Death NOS at 21.4%, sepsis at 14.3%, fever at 13.8%, blood bilirubin increased at 10.3%, and anemia at 7.1%. These entries describe terms recorded in the safety results; they do not establish that a study drug caused an event. A participant can experience more than one event, so event terms should not be treated as mutually exclusive categories unless the record explicitly says so. That detail is not reported in the registry record.
Interpretation is also limited by the absence of response denominators and outcome analyses. Without an estimate and its uncertainty, the posted information cannot show how precisely the arms differ on the primary endpoint. The design makes the comparison scientifically relevant, but design features do not substitute for the outcome results needed to answer the clinical question.
9. Statistical Methods Explained
What does randomization contribute?
Randomization assigns participants to study groups by a chance-based process. In general, this helps reduce systematic differences between groups at the point of assignment, including differences that investigators may not have measured. It supports a fair comparison of outcomes under the assigned regimens, provided the allocation and follow-up are handled appropriately. Randomization does not guarantee that every characteristic will be balanced in a particular trial, and it does not remove uncertainty from a study with a limited number of participants.
This study is listed as randomized and parallel. In a parallel design, participants are assigned to one regimen and outcomes are assessed in that group rather than having each participant receive both regimens in sequence. The two arms differ by the presence or absence of cobimetinib alongside atezolizumab and varlilumab. The registry identifies the study as unmasked, so masking is not part of the listed design. The record does not give further details about allocation procedures.
How should a response count be understood?
The primary endpoint is a count of participants meeting a response definition. Although the reported measure is a count, the underlying outcome is binary at the participant level: each participant is classified according to whether the criteria for complete or partial response are met. In general, a comparison of binary outcomes may describe the proportion meeting the definition in each group and the difference between groups. Those quantities require the outcome counts and the relevant group denominators. Neither arm’s primary response results nor its denominators are reported in the registry record.
RECIST v1.1 supplies the stated criteria for classifying response. The registry defines complete response as disappearance of all lesions and partial response as at least 30% decrease in the sum of target lesions. A prespecified, standardized rule helps clarify what qualifies as a response, but classification still depends on the assessments available and their timing. The record gives the primary outcome timeframe as up to 2 years; further details about the assessment schedule for this endpoint are not reported in the registry record.
What would uncertainty measures add?
In general, a confidence interval describes the range of effect estimates compatible with the data under the method used. It conveys precision as well as direction and magnitude: a wider interval indicates less precision, while a narrower interval indicates more precision. A p-value, when reported, addresses how compatible the observed data are with a specified null hypothesis under the analysis assumptions. Neither measure establishes clinical importance by itself. The registry record does not report a confidence interval, p-value, or other inferential result for the primary response comparison.
The absence of these estimates matters because counts alone, even when available, do not fully describe uncertainty. A difference between groups can be difficult to interpret without knowing the denominators, analysis method, and precision. In general, an analysis plan also clarifies whether the comparison is unadjusted or adjusted and how outcomes are handled when participants have missing assessments. Those details are not reported in the registry record.
Why distinguish observed results from planning calculations?
In general, a sample-size calculation is a design aid: it relates a planned number of participants to assumptions about an effect, variability, and a statistical decision rule. It is not a result observed from participants. A planning illustration based on an observed effect is retrospective and should not be confused with the trial’s original design justification. Any sample-size illustrations associated with this study are planning illustrations, not observed power. The registry record does not report the trial’s own sample-size justification, so the assumptions used to select its enrollment cannot be established from the record.
Power is a design concept describing the chance of detecting a specified effect under stated assumptions. It is not a measure of whether the observed result is reliable, and calculating “observed power” from an outcome estimate does not replace a confidence interval or a direct account of uncertainty. For this trial, the primary response result needed to describe an observed effect is not reported in the registry record.
What does the registry list about analyses?
The registry lists no analysis records. This means that an analysis method or inferential comparison is not presented in the registry record; it does not establish that investigators conducted no analyses outside the record. In particular, the record does not describe a statistical model for the primary endpoint, any adjustment for participant characteristics, or a strategy for multiple outcome testing. Those choices can affect how estimates are formed and interpreted, so their absence limits what can be concluded about the statistical analysis.
The study also lists several secondary outcomes, including adverse events and overall survival. Each outcome has its own measurement and interpretation. In general, safety counts summarize reported events or participants with events, whereas a time-to-event outcome such as overall survival requires information about follow-up and event timing. The registry record does not report analysis details or results for these secondary endpoints in the information. The design and definitions identify the questions the trial set out to examine; they do not supply the evidence needed to estimate those outcomes.
10. Multiplicity, Missing Data and Analysis Populations
The trial lists a primary response outcome and several secondary outcomes, including serious adverse events, overall survival, changes in T-cell populations and clearance rates, and anti-drug antibodies. When several outcomes are tested, the chance of at least one apparently notable result can increase. In general, a prespecified multiplicity strategy explains how investigators interpret results across several tests. No such strategy is reported in the registry record, and no analysis records are listed.
The primary response endpoint is defined, but the registry record does not report its arm-level results, denominators, or analysis population. It does not state whether the primary analysis includes all randomized participants, only participants who received treatment, or another group. It also does not report how participants with missing response assessments, incomplete follow-up, or other missing data were handled. These omissions make it impossible to determine from the record whether the reported analysis, if any, followed an intention-to-treat principle or another approach.
In general, missing outcomes can affect interpretation when the likelihood of missingness is related to a participant’s health or outcome. Statistical methods may use assumptions or sensitivity analyses to examine that uncertainty, but the registry record does not describe such methods for this endpoint. The record also does not report interim analyses or stopping rules. These absences should be read as unreported information, not as evidence that a particular method was or was not used outside the registry record.
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 |
|---|---|---|---|
| Arm A (Cobimetinib, Atezolizumab, Varlilumab) | 24 | 29 | 82.8% |
| Arm B (Atezolizumab, Varlilumab) | 25 | 28 | 89.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A (Cobimetinib, Atezolizumab, Varlilumab) | 21 of 29 |
| Arm B (Atezolizumab, Varlilumab) | 23 of 28 |
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 |
|---|---|
| Arm A (Cobimetinib, Atezolizumab, Varlilumab) | 25 of 29 |
| Arm B (Atezolizumab, Varlilumab) | 27 of 28 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A (Cobimetinib, Atezolizumab, Varlilumab) | Arm B (Atezolizumab, Varlilumab) |
|---|---|---|---|
| Disease progression | General disorders | 15 of 29 | 16 of 28 |
| Death NOS | General disorders | 4 of 29 | 6 of 28 |
| Sepsis | Infections and infestations | 2 of 29 | 4 of 28 |
| Blood bilirubin increased | Investigations | 3 of 29 | 2 of 28 |
| Fever | General disorders | 4 of 29 | 0 of 28 |
| Acute kidney injury | Renal and urinary disorders | 1 of 29 | 2 of 28 |
| Anemia | Blood and lymphatic system disorders | 0 of 29 | 2 of 28 |
| Abdominal pain | Gastrointestinal disorders | 2 of 29 | 0 of 28 |
| Nausea | Gastrointestinal disorders | 2 of 29 | 0 of 28 |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | 1 of 29 | 1 of 28 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A (Cobimetinib, Atezolizumab, Varlilumab) | Arm B (Atezolizumab, Varlilumab) |
|---|---|---|---|
| Lymphocyte count decreased | Investigations | 15 of 29 | 14 of 28 |
| Fatigue | General disorders | 12 of 29 | 10 of 28 |
| Vomiting | Gastrointestinal disorders | 13 of 29 | 8 of 28 |
| Anorexia | Metabolism and nutrition disorders | 8 of 29 | 13 of 28 |
| Diarrhea | Gastrointestinal disorders | 17 of 29 | 3 of 28 |
| Anemia | Blood and lymphatic system disorders | 11 of 29 | 8 of 28 |
| Platelet count decreased | Investigations | 10 of 29 | 9 of 28 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 11 of 29 | 6 of 28 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 11 of 29 | 6 of 28 |
| Nausea | Gastrointestinal disorders | 10 of 29 | 6 of 28 |
Serious events with the highest arm-level rate: disease progression (57.1%), death nos (21.4%), sepsis (14.3%), fever (13.8%), blood bilirubin increased (10.3%).
The registry lists serious adverse event counts as 24 of 29 participants at risk in Arm A and 25 of 28 in Arm B. For other adverse events, it lists 25 of 29 in Arm A and 27 of 28 in Arm B. It separately lists deaths as 21 in Arm A and 23 in Arm B. These are descriptive registry figures; they are not an adjusted comparison of treatment effects.
The record lists serious-event terms and percentages: disease progression, 57.1%; Death NOS, 21.4%; sepsis, 14.3%; fever, 13.8%; blood bilirubin increased, 10.3%; and anemia, 7.1%. The listed terms should not be assumed to represent mutually exclusive groups of participants. A participant may have multiple events, and the registry record does not explain the denominator or counting rules for each term in the information.
Adverse event reporting does not by itself establish that a study drug caused an event. The figures also do not show whether the groups differed in ways relevant to safety or whether the difference, if any, is precise. Interpretation would require the event definitions, follow-up context, and an appropriate comparison. Those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The trial’s design addresses a focused question: whether the response experience differs between atezolizumab plus varlilumab with cobimetinib and the same two-drug combination without cobimetinib in previously treated, unresectable biliary tract cancers. The primary endpoint and response criteria are stated, and the registry reports some safety counts. These details describe the planned comparison and part of the recorded safety information.
The registry record does not report the primary response counts by arm, an effect estimate, or an inferential analysis. Therefore, the posted information does not establish the direction or size of a response difference, nor how precisely such a difference could be estimated. The absence of reported results is not evidence of no difference, and it cannot support a conclusion that either regimen is superior or equivalent.
Response is also a distinct outcome from survival, duration of response, symptoms, or quality of life. The registry lists overall survival as a secondary outcome, but its results are not reported in the information. A response count alone would not answer those other questions. Likewise, the listed safety counts and terms describe events in the trial record but do not demonstrate that a treatment caused them or establish a comparative safety effect.
In general, a randomized design strengthens the basis for comparing groups, but interpretation still depends on complete outcome reporting, defined analysis populations, appropriate methods, and transparent uncertainty estimates. Those elements are not reported for the primary endpoint in the registry record. The scientifically relevant question is clear; the posted results are insufficient to answer it statistically.
13. Why This Trial Matters Statistically
This trial is statistically notable for a direct randomized comparison of two related regimens. Because atezolizumab and varlilumab appear in both arms, the intended contrast focuses on adding cobimetinib to that combination. The parallel-group randomized design provides a framework for estimating that contrast, rather than relying on comparisons across unrelated groups or studies.
The primary endpoint also has a defined clinical measurement rule: complete or partial response under RECIST v1.1 after at least one dose. A clear endpoint definition is important because statistical comparisons depend on how outcomes are classified. The study’s listed secondary outcomes broaden the questions to safety, overall survival, immune-cell populations, clearance rates, and anti-drug antibodies, but each requires its own results and analysis.
At the same time, the registry record illustrates why design information and outcome evidence must be distinguished. An enrollment of 57 and a randomized design do not reveal the treatment contrast, its precision, or whether the primary question is answered. The record lists no analysis records and does not report arm-level response results. The safety counts are descriptive and cannot substitute for the missing primary comparison.
In general, transparent reporting of denominators, effect estimates, uncertainty, analysis populations, and missing-data methods allows readers to judge both the magnitude and reliability of findings. Those details are not reported for the primary endpoint in the registry record. The trial’s design identifies an informative statistical question, while the posted information leaves that question unresolved.
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 principal limitation for interpretation is that the registry record does not report the primary response results by arm, the denominators for that outcome, or a statistical comparison. Although the outcome definition and timeframe are listed, they are not enough to estimate an effect or its precision. No analyses are listed in the registry record.
The record does not report the trial’s sample-size justification, detailed statistical analysis plan, analysis populations, or methods for handling missing response data. It also does not report whether interim analyses or a multiplicity strategy were planned. These details are relevant to understanding how the study was designed and how results should be interpreted, but their absence from the record does not establish what may have been done outside it.
The study is unmasked, as listed in the design. In general, lack of masking can matter for outcomes influenced by assessment or reporting, although the registry record does not provide information that would quantify any such influence in this trial. The arm descriptions are incomplete, so full regimen and assessment details cannot be reconstructed from the registry entry.
The safety information is limited to the listed counts and serious-event terms. The record does not provide enough context to establish causation, compare risk with precision, or determine whether event categories overlap. The death counts likewise should not be interpreted as a treatment effect. Finally, the listed enrollment and registry status do not by themselves establish completeness of follow-up or finality of all outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer — NCT04941287.
- Registry record last updated 2025-05-23; status last verified 2025-05.
- Results first posted 2025-05-23.
- 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
NCT04941287 is a randomized, unmasked, parallel-group phase 2 study sponsored by the National Cancer Institute. It enrolled 57 participants with previously treated, unresectable biliary tract cancers. Arm A received cobimetinib with atezolizumab and varlilumab; Arm B received atezolizumab and varlilumab without cobimetinib. The registry lists a start date of 2021-12-15, a primary completion date of 2024-01-02, and a status of active, not recruiting.
The primary outcome is the number of participants with a complete or partial response under RECIST v1.1, assessed up to 2 years. The registry record does not report arm-level response results or an analysis comparing the arms. It lists serious and other adverse event counts, deaths, and several serious-event terms, but these descriptive figures do not establish treatment causation or a comparative effect. The protocol’s sample-size justification and detailed statistical analysis plan are not reported in the registry record.