Study Description
A multicenter, open-label, continuous Phase 1b study in patients with metastatic breast cancer or locally advanced/recurrent breast cancer (mBC) to assess the safety, tolerability, and clinical activity of the study drug in combination with another two drugs. The study has a dose-escalation and expansion part. Approximately 148 patients were enrolled in the study. This includes approximately 40 patients in the dose-escalation portion and 108 response evaluable patients in the expansion portion.
Study Objectives
The endpoints of the study are Progression Free Survival, Duration of Response and Objective Response Rate. Objective response status at each evaluation (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD] or not evaluable [NE]) will be defined according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) guidelines as assessed by investigators. Swimmer plot, Waterfall plot and Kaplan-Meier plots are generated to represent these objectives graphically.
Efficacy Endpoint Visualization
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Swimmer plot with horizontal bars where each bar represents each corresponding subject is produced to present time to first response, duration of treatment, and duration of response graphically by treatment arm.
Subjects are taken in the Y-axis and Time(months) since First Dose is taken in the X-axis. Each bar is presented for each patient starting from first dose date to last dose date, EOS date, death date, whichever occurs last. The time(months) in which PR started (Partial Response Start), SD started (Stable Disease Start), Progression started, Death occurred are represented as different shapes(inverted triangles, circles, squares).
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Interpretation
From the plot, it is visible that the longest duration for a single participant in the study is around 33 months. This subject has Stable disease starting around 2nd month and Partial response starting around 4th month. There are 4 subjects who have died during the study.
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Waterfall plot of maximum percent reduction in the sum of longest diameter for non-nodal lesions and short axis for nodal lesions from baseline is created by treatment arm. These plots display the best percentage change from baseline in the sum of the diameter of all target lesions for each patient in the Response Evaluable Analysis set.
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Best percentage improvement is taken in the Y-axis and each bar in the X-axis represents each subject. The legend represents the best overall response for the subject. Best overall response is derived based on the best response among individual time point responses given by Investigator.
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Interpretation
For the first subject, a long red bar represents that the best overall response is “Progressive Disease” and best percentage improvement is 40%. For this subject, best percentage is in upward direction which means that the sum of diameters of target lesion is increased. For rest of the subjects, the best overall responses are either SD, uPR or PR and the direction of bars indicates the tumor shrinkage. Best percentage change is -100% for 4 participants which means that the target tumor disappeared for those subjects.
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Kaplan Meier plot which summarizes the Progression Free Survival (PFS) data. PFS is the time from date of first dose to date of first documentation of progression or death due to any cause. CIs for median PFS will be estimated using the Brookmeyer-Crowley method. CIs for estimated probabilities of event by specific times will use log(-log) method.
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Progression Free Survival rate is taken in the Y-axis and month is taken in the X-axis. The “+” sign indicates that the subject is censored in the study at a given month. Each step observed in the graph indicates if an event (Here, the event of interest is “Progressive Disease/Death”) has occurred.
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Interpretation
Wild Type, Mutated are two categories of Baseline PIK3CAST mutation status. The “Median Time (in months)” represents the time beyond in which half of the population under consideration may not survive. The bottom part shows the number of subjects at risk, who has no event/censor and may experience PD in the successive months. Since there are not enough subjects in the mutated category, the median time is represented as NA.
Safety Data Point Visualization
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Bar plot of Serious AEs by treatment group
In the case of serious AEs, treatment group XX3 is dominating as compared to treatment groups XX1 and XX2. Among the serious AEs around 54% of them have happened in XX3 and 31% happened in group XX2 and 15% happened in treatment group XX1.
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Histogram- No. of subjects by sex and race.
Majority of the subjects belong to white. And the male to female ratio is 11:25.
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Heatmap of No. of AEs per system organ class (SOC) per treatment groups
The SOC, Gastrointestinal disorder have a notable No. of adverse events Terms in three treatment groups. For all other SOC, only a small no. of adverse events are observed.
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Heatmap of No. of serious AEs per system organ class (SOC) per treatment groups
Serious AEs are observed in three system organ class, Infections and infestations, Gastrointestinal disorder and Blood and lymphatic system disorders. Among these, Gastrointestinal disorder is frequent and is more observed in treatment group XX3.
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Box plot of age by sex and race
Minimum age of subject participated in study is 19 and max age of subject is 65.
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Scatter plot of Height and weight by sex
