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 A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Participants With Advanced Solid Tumors (NCT03666143), a na phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03666143 |
| Phase | Phase 1 |
| Condition | Advanced Solid Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 216 |
| Arms in the primary outcome | n/a |
| Lead sponsor | BeiGene |
| Results posted | Yes |
2. Clinical Question
Population
Participants with histologically or cytologically confirmed locally advanced or metastatic tumors. The registry description includes non-squamous or squamous non-small cell lung cancer, renal cell carcinoma, ovarian cancer, or melanoma. The broader condition is advanced solid tumors.
Intervention
Sitravatinib 120 mg orally once daily in combination with tislelizumab 200 mg intravenously once every 3 weeks. The registry describes an open-label study of the combination.
Comparator
There was no separate comparator group. The study is listed as non-randomized and single-group, so its results do not provide a like-for-like comparison with another treatment or with no treatment.
Primary question
How many participants in the Safety Analysis Set experienced treatment-emergent adverse events or serious adverse events during the defined safety observation period? The endpoint is a participant count, not a comparison of treatment effects.
The registry frames the study as an assessment of safety, tolerability, pharmacokinetics, and preliminary antitumor activity. Its primary outcome is the number of participants with adverse events. Listed secondary outcomes include objective response rate, duration of response, disease control rate, progression-free survival, and pharmacokinetic measures for sitravatinib. The record does not report analyses for those secondary outcomes. Thus, the posted results address a limited part of the broader set of questions: they give adverse-event counts and selected serious-event terms, but do not establish how the combination compares with another approach or provide reported estimates of antitumor activity.
3. Trial Design
NCT03666143 is a completed Phase 1b, open-label, multicenter, non-randomized, single-group study sponsored by BeiGene. The registry lists enrollment of 216 participants. The study began on 2018-11-01, and primary completion is recorded as 2023-01-05. Participants received the combination of sitravatinib and tislelizumab; the recorded schedule was sitravatinib 120 mg orally once daily and tislelizumab 200 mg intravenously once every 3 weeks.
The registry describes participants as having histologically or cytologically confirmed locally advanced or metastatic tumors, including non-squamous or squamous non-small cell lung cancer, renal cell carcinoma, ovarian cancer, or melanoma. Although the condition is listed broadly as advanced solid tumors, these specified tumor types indicate the settings represented in the study description. The record does not give a breakdown of enrollment or results by tumor type.
Open-label means that treatment masking was not used, and single-group means the registry lists one treatment group rather than randomized study arms. These features matter when interpreting the posted counts: there is no concurrent control group for separating treatment-associated events from events that might occur in a comparable group for other reasons. The design can describe observed safety experience among participants who received study drug, but it cannot, by itself, estimate a comparative effect against an alternative.
The Safety Analysis Set is defined as all participants who received at least one dose of any study drug. The registry reports 216 participants at risk for both serious and other adverse-event counts in the combination group. The record does not report a protocol-level sample-size justification, randomization procedure, allocation plan, or detailed statistical analysis plan. It lists several secondary outcomes, but no analyses for those outcomes are reported in the registry record.
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 | Sitravatinib + Tislelizumab |
|---|---|
| STARTED | 216 |
| COMPLETED | 0 |
| NOT COMPLETED | 216 |
Reasons for not completing this period:
| Reason | Sitravatinib + Tislelizumab |
|---|---|
| Death | 158 |
| Sponsor Decision | 31 |
| Withdrawal by Subject | 11 |
| Lost to Follow-up | 5 |
| Physician Decision | 1 |
| Rolled into extension study | 9 |
| Progressive Disease | 1 |
Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set is defined as all participants who received at least 1 dose of any study drug (any component of the combination therapy)
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 | Sitravatinib + Tislelizumab |
|---|---|---|
| Participants analysed | 216 | |
| Age, Continuous | Years | 60.2 (SD 11.03) |
| Sex: Female, Male: Female | Participants | 103 |
| Sex: Female, Male: Male | Participants | 113 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 213 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 143 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 2 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 70 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), measured over Up to approximately 4 years and 2 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants with adverse events. It includes treatment-emergent adverse events and serious adverse events, with assessment described as encompassing laboratory tests, physical examinations, electrocardiogram results, and vital signs. A treatment-emergent adverse event is defined in the registry as an event that began, or worsened in severity from baseline, on or after the first dose of study drug and up to 30 days following the last dose or the start of a new anticancer therapy, whichever occurred first.
The endpoint is a count of participants, rather than a measure of how often events occurred per unit of time or how severe each participant’s overall experience was. A participant-level count indicates whether participants experienced events under the endpoint definition; it does not, on its own, describe the number of events each participant experienced. Serious and other adverse events are reported separately in the posted safety results.
In general, safety endpoints are used to characterize the types and extent of adverse events observed during treatment and follow-up. The registry’s stated population is the Safety Analysis Set: participants who received at least one dose of any component of the combination. The posted count therefore pertains to treated participants as defined by that set, not necessarily every person enrolled. The record does not report additional endpoint details such as adjudication procedures or a separate severity grading summary.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures describe participants in the single combination group. The registry lists 216 participants at risk for serious adverse events and 120 participants with serious adverse events. It also lists 216 at risk for other adverse events and 213 participants with other adverse events. These are counts, not comparative estimates. Because the study has no control group, the counts cannot show how the experience differs from that of participants receiving another treatment or no study treatment.
Among the serious adverse-event terms listed, the registry reports Diarrhoea at 5.1%, Pneumonia at 4.6%, Death at 4.2%, Abdominal pain at 3.7%, Pyrexia at 3.7%, and Vomiting at 3.2%. These are selected terms, not a complete list of every serious event. The posted figures also list 158 deaths. The registry information does not establish the cause of each death or whether a death was attributed to study treatment. A listed event, including Death as a serious-event term, should not be interpreted as proof of causation.
The primary endpoint is framed as a number of participants with adverse events, with treatment-emergent events defined by timing relative to dosing and a post-treatment window. That definition is important: it specifies which events enter the count, but it does not establish that treatment caused them. The count also does not distinguish the number of events experienced by each participant or convey event duration. Those questions require additional information not reported in the registry record.
No uncertainty intervals, hypothesis tests, or adjusted estimates for the primary outcome are reported in the registry record. Without such estimates, the precision of the observed counts cannot be summarized by a reported confidence interval. General statistical interpretation would account for uncertainty around counts, particularly when considering specific event terms, but no such interval should be inferred from the posted counts alone.
The record lists objective response rate, duration of response, disease control rate, progression-free survival, and pharmacokinetic outcomes as secondary outcomes. It reports no analyses for these outcomes. Consequently, the posted results do not give an estimate of antitumor activity or a comparative efficacy result. The appropriate interpretation is limited to the reported safety counts and event terms within the enrolled, treated group, with the design and reporting gaps kept in view.
9. Statistical Methods Explained
What does a participant count represent?
The primary outcome is a count of participants who experienced adverse events, rather than a count of all event episodes. In general, a participant-level binary outcome classifies each person according to whether the specified event criterion was met. This can be useful for describing how many treated participants experienced at least one event in a category. It does not show how many events each participant had, how long an event lasted, or whether several events occurred in the same person.
The registry describes both treatment-emergent and serious adverse events. Treatment-emergent status is based on event onset or worsening relative to baseline and a defined period around study-drug exposure. Seriousness is a separate classification. An event can be assessed for seriousness and for its timing, and those labels answer different questions. The posted results distinguish serious-event counts from other-event counts, but the registry record does not report enough detail to reconstruct every classification rule or the participant-level overlap between categories.
Why does the denominator matter?
A count is interpreted in relation to the population at risk. For the primary safety analysis, the registry defines the Safety Analysis Set as participants who received at least one dose of any study drug. It lists 216 participants at risk in the combination group for serious events and 216 for other events. Counts without their population context would be difficult to interpret; the stated at-risk population anchors the reported safety experience to treated participants.
In general, a count and denominator together can describe the observed frequency in a study group, but no additional rate or percentage should be inferred unless it is reported or explicitly calculated in the posted results. The safety information gives selected serious-event percentages directly. It does not report uncertainty intervals for those figures. For event terms that occur infrequently, estimates can be imprecise; a confidence interval, when reported, would express a range of values compatible with the data under the specified method. No interval is reported for these event terms.
What can a single-group design estimate?
This trial is listed as single-group, non-randomized, and open-label. In general, a single-group study can describe outcomes observed among participants receiving the intervention. It does not offer a concurrent control group that would help distinguish outcomes associated with treatment from outcomes related to the disease, background risks, other care, or chance. A descriptive count is therefore not the same as an estimate of a treatment effect.
Random allocation, when used, can help make groups comparable on average, while masking can reduce some influences on assessment and reporting. Neither feature supplies a guarantee of unbiased results, and this registry record lists neither randomization nor masking. The lack of a comparator is especially relevant for adverse events, since the observed events cannot be contrasted with a control-group experience within this study. The registry does not report an external comparison or an adjusted analysis.
How should the event percentages be read?
The listed percentages accompany selected serious adverse-event terms. They should be read as the registry’s reported values, not as estimates of causal risk attributable to the combination. The record does not provide confidence intervals or a detailed account of how the selected terms were chosen. A selected list can highlight common or notable terms but does not represent the full safety profile, and absence from this list does not establish that an event did not occur.
Likewise, the recorded count of deaths should be distinguished from a treatment-related death count. The record reports the number of deaths but does not state that every death was caused by treatment. Determining attribution generally requires clinical review and specified criteria; those details are not reported in the registry record. Counts should be described as observed safety data, not as causal conclusions.
What does the registry report about inference?
The registry record reports no analyses for the listed outcomes. It does not report a statistical analysis plan, hypothesis tests, adjusted estimates, confidence intervals, or missing-data procedures. Without these details, there is no basis for describing a formal inferential test or a prespecified model for the primary safety endpoint. This is not evidence that a particular analysis was or was not conducted outside the registry; it means that the analysis is not reported in the registry record.
In general, confidence intervals communicate uncertainty around an estimate, while hypothesis tests assess data relative to a specified null hypothesis under stated assumptions. Neither can be reconstructed responsibly from a count alone without choosing assumptions and methods. Any such calculation would be a new analysis, not a registry-reported result. The posted information should therefore be read descriptively.
Why is over-dispersion relevant in general?
For count data that record repeated event episodes, a simple model may assume that variability follows a particular relationship to the mean. Over-dispersion means the observed variation is greater than that assumption allows; failing to account for it can make uncertainty appear too small. This is a general consideration for event counts, not a reported finding in this trial. The primary endpoint is described as the number of participants with events, and the registry does not report a model for repeated event counts or an over-dispersion assessment.
The participant-level count also differs from time-to-event analysis. A time-to-event approach uses information about when an outcome occurs and can account for differing follow-up under specified assumptions. Although progression-free survival and duration of response are listed among secondary outcomes, no analyses are reported for them. The registry’s adverse-event counts do not provide the timing detail needed to interpret them as time-to-event estimates.
How should planning illustrations be separated from results?
Sample-size planning illustrations based on an observed effect are hypothetical calculations under stated assumptions. They are not the trial’s actual design justification, do not describe what was observed, and are not observed power. In general, a planning calculation asks how many participants might be needed to detect a specified effect under an assumed statistical model and design. It does not change the meaning of the results from the participants enrolled in this single-group study.
The registry record does not report the trial’s sample-size justification or a comparative effect estimate for the safety endpoint. Accordingly, any planning illustration should be treated only as a separate hypothetical exercise, not evidence that the study had a particular probability of detecting an effect or that a treatment effect was established.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, including objective response rate, duration of response, disease control rate, progression-free survival, and several pharmacokinetic measures for sitravatinib. It reports no analyses for these outcomes. The registry record does not report a multiplicity adjustment, a hierarchy of tests, or a prespecified strategy for controlling false-positive findings across multiple outcomes. Without reported analyses and a stated testing plan, no inference about multiplicity control can be made.
Missing-data methods are not reported in the registry record. The safety population is defined as participants who received at least one dose of any study drug, but the record does not describe how incomplete safety assessments, withdrawals, or missing outcome values were handled. The length of each participant’s observation may also differ; the registry’s event definition specifies a treatment-related observation window, but does not provide participant-level follow-up or completeness information in the posted results.
The record does not report whether analyses were adjusted for baseline characteristics, tumor type, or other factors. No subgroup analysis results are listed. Therefore, the reported counts should not be understood as adjusted estimates or as results for each tumor type separately. The registry information also does not report a detailed analysis population for the listed secondary outcomes.
These omissions constrain statistical interpretation. They do not establish that a particular method was used or that data were missing; they indicate that these procedures and details are not reported in the registry record. The adverse-event counts can be described as posted, but broader claims about model-based estimates, multiplicity-adjusted findings, or missing-data robustness would require information not present in the 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 |
|---|---|---|---|
| Sitravatinib + Tislelizumab | 120 | 216 | 55.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sitravatinib + Tislelizumab | 158 of 216 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sitravatinib + Tislelizumab | 213 of 216 |
Most frequent serious adverse event terms
| Event term | Organ system | Sitravatinib + Tislelizumab |
|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 11 of 216 |
| Pneumonia | Infections and infestations | 10 of 216 |
| Death | General disorders | 9 of 216 |
| Abdominal pain | Gastrointestinal disorders | 8 of 216 |
| Pyrexia | General disorders | 8 of 216 |
| Vomiting | Gastrointestinal disorders | 7 of 216 |
| Small intestinal obstruction | Gastrointestinal disorders | 6 of 216 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 5 of 216 |
| Ascites | Gastrointestinal disorders | 4 of 216 |
| Intestinal obstruction | Gastrointestinal disorders | 4 of 216 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sitravatinib + Tislelizumab |
|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 114 of 216 |
| Alanine aminotransferase increased | Investigations | 101 of 216 |
| Aspartate aminotransferase increased | Investigations | 97 of 216 |
| Weight decreased | Investigations | 82 of 216 |
| Hypertension | Vascular disorders | 81 of 216 |
| Hypothyroidism | Endocrine disorders | 71 of 216 |
| Decreased appetite | Metabolism and nutrition disorders | 71 of 216 |
| Nausea | Gastrointestinal disorders | 67 of 216 |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 63 of 216 |
| Vomiting | Gastrointestinal disorders | 57 of 216 |
Serious events with the highest arm-level rate: diarrhoea (5.1%), pneumonia (4.6%), death (4.2%), abdominal pain (3.7%), pyrexia (3.7%).
The combination group has 216 participants listed at risk for serious adverse events, with 120 participants reported as having serious adverse events. For other adverse events, 216 are listed at risk and 213 participants are reported as affected. These are participant counts in the registry’s safety reporting, not counts of all event episodes. The record does not explain the overlap between the serious and other categories, so the two counts should not be added or treated as mutually exclusive.
The selected serious-event terms are Diarrhoea, 5.1%; Pneumonia, 4.6%; Death, 4.2%; Abdominal pain, 3.7%; Pyrexia, 3.7%; and Vomiting, 3.2%. These terms and percentages are the registry’s selected entries, not a complete listing of all serious events. The registry also reports 158 deaths. It does not report the cause of each death or attribute all deaths to the study drugs. The term Death within the serious-event list and the overall death count should not be treated as proof that treatment caused those outcomes.
In general, safety counts describe what was observed in the defined population and observation period. They do not, without a comparator and further analysis, estimate excess risk due to treatment. The event definition extends to 30 days following the last dose or initiation of a new anticancer therapy, whichever occurs first; interpretation should retain that stated boundary.
12. What the Result Does, and Does Not, Mean
The posted data show that adverse events were recorded among participants in the sitravatinib-plus-tislelizumab group. The registry reports 120 participants with serious adverse events and 213 with other adverse events, each among 216 participants listed at risk. It also lists selected serious-event terms and reports 158 deaths. These figures describe observed events in the defined safety population; they do not establish that the study drugs caused a particular event or death.
The study’s single-group, non-randomized design means there is no concurrent comparison group. The counts therefore cannot show whether the frequency of an event was higher or lower than it would have been under another treatment, nor can they isolate the contribution of either drug. The open-label design and absence of a control group are important when interpreting event reporting and assessment.
The registry’s stated scientific scope includes safety, tolerability, pharmacokinetics, and preliminary antitumor activity. Although response, disease-control, duration, progression-free survival, and pharmacokinetic outcomes are listed, the registry record does not report analyses for them. The posted safety results should not be used to claim benefit or lack of benefit on those outcomes. Nor do the results establish comparative effectiveness.
In general, an observed count is a description of study participants, while a causal treatment effect requires a design and analysis that support a comparison. Precision also matters: confidence intervals and other uncertainty estimates are not reported for the primary outcome in the registry record. Thus, the posted data permit a descriptive account of safety counts but do not provide a complete estimate of uncertainty, a causal conclusion, or an efficacy conclusion.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between safety description and comparative treatment evaluation. Its primary outcome is a participant count, and the record supplies counts for serious and other adverse events in the treated group. Such data can characterize the types of events recorded during a study and help readers understand the observed safety experience in the defined population.
The design also sets clear limits on the conclusions. A single-group study does not estimate a contrast against a concurrent control group, so observed event counts cannot be interpreted as the difference attributable to treatment. This is not a technicality: a count describes the study group, while a treatment effect describes how outcomes compare under different treatment conditions. The registry record provides the former, not the latter.
The study’s broad stated aims include pharmacokinetics and preliminary antitumor activity, and the registry lists several outcomes related to those aims. Yet no outcome analyses are reported in the registry record. This illustrates why outcome listings and outcome results must be distinguished. A listed measure identifies an intended area of assessment but does not itself supply an estimate, uncertainty interval, or evidence of an effect.
Finally, safety reporting benefits from careful attention to definitions and population. The treatment-emergent window, the treated Safety Analysis Set, and the distinction between serious and other adverse events shape what the counts mean. The reported information is useful for descriptive interpretation, while missing comparative, inferential, and attribution details limit stronger conclusions. Keeping those statistical boundaries explicit is central to a balanced reading of early-phase clinical evidence.
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 comparator group, randomization, or masking. As a result, the posted safety counts cannot support a direct treatment comparison. The open-label, single-group design also leaves no concurrent basis for separating events associated with treatment from events arising from the underlying conditions, other care, or background risk.
The record reports no analyses for the listed secondary outcomes, including response, duration of response, disease control, progression-free survival, and pharmacokinetic measures. It also does not report confidence intervals, hypothesis tests, adjusted estimates, or subgroup analyses. Efficacy and pharmacokinetic conclusions therefore cannot be drawn from the posted results.
Safety information is limited to participant counts and selected serious-event terms. The record does not report participant-level event histories, overlap between serious and other-event categories, event duration, or cause and treatment attribution for deaths. It does not provide detailed missing-data procedures or a full account of safety follow-up completeness. Although the primary outcome defines a treatment-emergent period, the posted counts do not offer individual timing information.
The study description includes several tumor types, but the registry does not report safety results broken down by tumor type. The stated enrollment is 216, and the posted safety results list 216 at risk in the combination group; the record does not provide further detail about enrollment flow or exclusions from the Safety Analysis Set. These reporting limitations do not invalidate the counts, but they constrain their scope. They should be read as descriptive results for the reported treated group, not as a complete safety characterization or a causal estimate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase 1b Study to Assess Sitravatinib in Combination With Tislelizumab in Participants With Advanced Solid Tumors — NCT03666143.
- Registry record last updated 2024-11-04; status last verified 2024-10.
- Results first posted 2024-06-17.
- 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
NCT03666143 is a completed, open-label, multicenter, non-randomized Phase 1b study of sitravatinib plus tislelizumab in advanced solid tumors. The registry lists enrollment of 216 and a single treatment group receiving sitravatinib 120 mg orally once daily with tislelizumab 200 mg intravenously once every 3 weeks.
The primary outcome is the number of participants with treatment-emergent adverse events and serious adverse events. The registry reports 120 participants with serious adverse events and 213 with other adverse events, among 216 at risk for each category. It lists selected serious-event terms and reports 158 deaths. These findings are descriptive; the single-group design provides no concurrent treatment comparison, and the record does not report causal attribution for deaths.
Several secondary outcomes are listed, but their analyses are not reported in the registry record. Confidence intervals, hypothesis tests, multiplicity procedures, and missing-data methods are also not reported. The results therefore support a limited description of posted safety counts, not comparative or efficacy conclusions.