Trial Outcomes & Findings for Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations (NCT NCT03040986)

Last Updated: 2021-02-09

Results Overview

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm (\<1 cm). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Approximately 1-8.2 months

Results posted on

2021-02-09

Participant Flow

180 pts were not enrolled to the study. All pts who made contact to participate in the study all had KRAS G12R mutation testing thus pre-screening was not necessary. The 1st 8 pts who made contact with the study and were eligible were consented, enrolled and treated. No other pts were enrolled in the study per the statistical design in the protocol. As pre-specified, the study did not move into the second phase due to lack of efficacy.

Participant milestones

Participant milestones
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	6	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Hospice	1	0
Overall Study Adverse Event	2	1
Overall Study Disease progression on study	3	1

Baseline Characteristics

Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	62 years STANDARD_DEVIATION 8.99 • n=5 Participants	59 years STANDARD_DEVIATION 7.07 • n=7 Participants	60.5 years STANDARD_DEVIATION 8.03 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants
Location of Primary Tumor Head/Body	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Location of Primary Tumor Tail	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Previous Treatments Radiation	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Previous Treatments Surgery	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Previous Treatments Multiple agents systemic chemotherapy	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Number of Previous Lines of Systemic Chemotherapy 1	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Number of Previous Lines of Systemic Chemotherapy 2	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Number of Previous Lines of Systemic Chemotherapy ≥3	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Number of Metastatic Sites (involved organs) 1	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Number of Metastatic Sites (involved organs) 2	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Number of Metastatic Sites (involved organs) ≥3	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 1-8.2 months

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Proportion of Participants With an Objective Response (Partial Response + Complete Response) Partial Response	0 Proportion of participants	0 Proportion of participants
Proportion of Participants With an Objective Response (Partial Response + Complete Response) Complete Response	0 Proportion of participants	0 Proportion of participants

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first, assessed up to 52 weeks

Population: All participants are grouped together as pre-specified in the protocol for this outcome measure.

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first and was calculated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=8 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Median Progression-free Survival (PFS)	3.0 Months Interval 0.8 to 8.2	—

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 25 months and 6 days.

Here are the grade 3 or greater adverse events assessed by the CTCAEv5.0 probably or definitely attributable to the agent Selumetinib. Grade 3 is defined as severe or medically significant, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event. Probably is defined as likely related to the agent, and Definitely is defined as clearly related to the agent.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib Probably: Grade 3 Hypertension	2 Adverse events	0 Adverse events
Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib Probably: Grade 3 Pancreatitis	1 Adverse events	0 Adverse events
Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib Definitely: Grade 3 Alanine aminotransferase increased	0 Adverse events	2 Adverse events
Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib Definitely: Grade 3 Dyspnea	1 Adverse events	0 Adverse events
Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib Definitely: Grade 3 Heart failure	1 Adverse events	0 Adverse events
Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib Definitely: Grade 3 Hypertension	0 Adverse events	1 Adverse events

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 25 months and 6 days.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).	6 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: This outcome measure was not done because only 1 out of the 8 enrolled participants agreed to undergo biopsy while on treatment. Tumoral biopsies were not mandatory but optional for participants enrolled onto the study. Because only one biopsy specimen was obtained, on the discretion of the PI, no analysis and no comparisons were performed.

Comparisons will be done to estimate the differences of the expression level in pancreas cancer tissues and clinical outcome variables.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: Since no responses were observed in either Arm/Group, the planned correlation was not conducted for this outcome measure.

Presence of variants identified in the 50-cancer gene panel will be compared with response, presenting the results in a 2x2 table with findings reported descriptively. Pre-treatment ctDNA levels will be divided into groups to separate aberrant values from the rest. The cutoffs will be \> and \< 2 standard deviations of the mean, with the cutoffs applied to both ctDNA levels. Based on these groups, resulting in participants with cell free deoxyribonucleic acid (cfDNA) transcripts levels \> 2 standard deviation (SD) above the mean, participants with cfDNA transcripts levels \< 2 SD below the mean, and the rest in between, the categorical results will be evaluated and reported relative to response vs. non-response in a descriptive manner.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: start of treatment every (q)2 weeks, up to 52 weeks

Population: This outcome measure was not done because of the lack of ctDNA copy number determinations in participants on-treatment compared to pre-treatment levels in the participants whose ctDNA levels were longitudinally evaluable. No variant profiling of baseline tumoral tissues was performed.

Circulating free deoxyribonucleic acid (cfDNA) transcript levels will be followed from the start of treatment every (q)2 weeks and the change to pre-treatment will be plotted for each timepoint in a spider plot format. Variant profile derived from voluntary repeat biopsies will be compared to pre-treatment variant profile and gain of variants (adjusted for similar sequencing depth) will be recorded.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 52 weeks

Population: No other somatic variants in ctDNA other than the KRAS allele were analyzed because the only available droplet digital PCR (ddPCR) assay was the one for the KRAS allele. Thus, the planned analysis change in the somatic ctDNA mutation profile and its correlation with clinical outcome was not conducted.

The presence of mutant DNA copies and the fractional abundance of the mutant KRAS allele on circulating tumor DNA (ctDNA) in cell-free (cf) DNA isolated from plasma samples were to be determined.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and the last KRAS value before the participant came off treatment, approximately 1- 8.2 months.

ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined from baseline and the last KRAS value (as a single value) before the participant came off treatment.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Mean Copy Number KRAS Wild Type Allele in Circulating Tumor DNA (ctDNA) Baseline	2584 copies Standard Deviation 2242	1556 copies Standard Deviation 480
Mean Copy Number KRAS Wild Type Allele in Circulating Tumor DNA (ctDNA) Last recorded value	6607 copies Standard Deviation 6067	1542 copies Standard Deviation 586

SECONDARY outcome

Timeframe: Approximately 1- 8.2 months.

Overall ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Percentage Change (%) of Copies KRAS Wild Type Allele	156 Percentage change	-1 Percentage change

SECONDARY outcome

Timeframe: Baseline and last recorded value while on treatment, approximately 1- 8.2 months.

Mean ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined at baseline and the last recorded value while on treatment.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Mean Copy Number KRAS Mutant Type Allele in Circulating Tumor DNA (ctDNA) Baseline	3.33 copies Standard Deviation 3.79	0 copies Standard Deviation 0
Mean Copy Number KRAS Mutant Type Allele in Circulating Tumor DNA (ctDNA) On Treatment	10.33 copies Standard Deviation 15	1.6 copies Standard Deviation 0.8

SECONDARY outcome

Timeframe: Approximately 1- 8.2 months.

Overall ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Percentage Change of Copies KRAS Mutant Type Allele	210 Percentage change	NA Percentage change The percentage was not calculable because the denominator had a value of 0.

SECONDARY outcome

Timeframe: Between baseline and last recorded value while on-treatment, approximately 1- 8.2 months.

This outcome measure is reporting the overall percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples between baseline and on-treatment.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Percentage of KRAS Allele in Circulating Tumor DNA (ctDNA) That is Identified as Variant From Cell-free (cf) DNA Baseline	7.5 Percentage Standard Deviation 8.7891979156235	0 Percentage Standard Deviation 0
Percentage of KRAS Allele in Circulating Tumor DNA (ctDNA) That is Identified as Variant From Cell-free (cf) DNA Last recorded value	9.33 Percentage Standard Deviation 14.185281887302	8.5 Percentage Standard Deviation 8.5

SECONDARY outcome

Timeframe: Approximately 1- 8.2 months.

Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value while on-treatment

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Any Percent Change in (VAF, %), of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA)	19.6 Percentage change	8.5 Percentage change

SECONDARY outcome

Timeframe: Baseline and last recorded value while on-treatment, approximately 1- 8.2 months.

Population: Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.

Any change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=3 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Mean Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline Baseline	0 Variant Allele Fraction (VAF, %) of KRAS Standard Deviation 0	0 Variant Allele Fraction (VAF, %) of KRAS Standard Deviation 0
Mean Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline Last recorded value	0 Variant Allele Fraction (VAF, %) of KRAS Standard Deviation 0	8.5 Variant Allele Fraction (VAF, %) of KRAS Standard Deviation 8.5

SECONDARY outcome

Timeframe: Approximately 1- 8.2 months.

Population: Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=3 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline	0 Percentage change	8.5 Percentage change

SECONDARY outcome

Timeframe: Baseline and last recorded value after treatment, approximately 1- 8.2 months.

Population: Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline and after treatment

This outcome measure is reporting the percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value after treatment in patients with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) (Mutant Fractional KRAS Abundency at baseline and after treatment (VAF %), KRAS allele at baseline \> 0%).

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Percentage Change of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA) That is Identified as Variant From Cell-free (cf) DNA at Baseline and After Treatment Baseline	18 Percentage change Standard Deviation 6	—
Percentage Change of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA) That is Identified as Variant From Cell-free (cf) DNA at Baseline and After Treatment Last recorded value	28 Percentage change Standard Deviation 9	—

SECONDARY outcome

Timeframe: Approximately 1- 8.2 months.

Population: Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment

Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) between baseline and last recorded value after treatment.

Outcome measures

Outcome measures
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=2 Participants Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants With Detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment	60.9 Percentage change	—

Adverse Events

Dose Level 0: 75mg Selumetinib Sulfate Twice Daily

Serious events: 3 serious events

Other events: 6 other events

Deaths: 5 deaths

75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily

Serious events: 0 serious events

Other events: 2 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 participants at risk Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 participants at risk Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Colonic obstruction	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Psychiatric disorders Confusion	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Infections and infestations Gallbladder infection	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Hepatobiliary disorders Gallbladder obstruction	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Cardiac disorders Heart failure	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Lipase increased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Pancreatitis	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Serum amylase increased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.

Other adverse events

Additional Information

Dr. Udo Rudloff

National Cancer Institute

Phone: 240-760-6238

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Dose Level 0: 75mg Selumetinib Sulfate Twice Daily n=6 participants at risk Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.	75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily n=2 participants at risk Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Abdominal distension	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Abdominal pain	50.0% 3/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Alanine aminotransferase increased	50.0% 3/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	100.0% 2/2 • Number of events 10 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Alkaline phosphatase increased	50.0% 3/6 • Number of events 5 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Skin and subcutaneous tissue disorders Alopecia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Blood and lymphatic system disorders Anemia	50.0% 3/6 • Number of events 5 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Anorexia	50.0% 3/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Ascites	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Aspartate aminotransferase increased	100.0% 6/6 • Number of events 9 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	100.0% 2/2 • Number of events 5 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Respiratory, thoracic and mediastinal disorders Atelectasis	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Musculoskeletal and connective tissue disorders Back pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Infections and infestations Biliary tract infection	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Bloating	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Blood bilirubin increased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations CPK increased	33.3% 2/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Creatinine increased	33.3% 2/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Nervous system disorders Dizziness	33.3% 2/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Dry mouth	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Nervous system disorders Dysgeusia	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Dysphagia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	50.0% 3/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
General disorders Edema face	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
General disorders Edema limbs	83.3% 5/6 • Number of events 6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
General disorders Edema trunk	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
General disorders Fatigue	66.7% 4/6 • Number of events 5 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
General disorders Fever	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Flatulence	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	100.0% 2/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
General disorders Generalized muscle weakness	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Glucose intolerance	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Hyperglycemia	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Vascular disorders Hypertension	66.7% 4/6 • Number of events 10 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	100.0% 2/2 • Number of events 5 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Hypoalbuminemia	83.3% 5/6 • Number of events 7 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Hypocalcemia	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Hypokalemia	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Hypomagnesemia	16.7% 1/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Metabolism and nutrition disorders Hyponatremia	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Vascular disorders Hypotension	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Lipase increased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Lymphocyte count decreased	33.3% 2/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
General disorders Malaise	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Musculoskeletal and connective tissue disorders Muscle weakness trunk	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, muscle spasm	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Nausea	50.0% 3/6 • Number of events 4 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Musculoskeletal and connective tissue disorders Neck pain	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Neutrophil count decreased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Pancreatitis	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Nervous system disorders Paresthesia	16.7% 1/6 • Number of events 3 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Infections and infestations Peritoneal infection	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Platelet count decreased	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Respiratory, thoracic and mediastinal disorders Pleural effusion	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Respiratory, thoracic and mediastinal disorders Postnasal drip	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/6 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	100.0% 2/2 • Number of events 3 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Skin and subcutaneous tissue disorders Rash acneiform	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	100.0% 2/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Renal and urinary disorders Renal and urinary disorders - Other, Dysuria	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Serum amylase increased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Respiratory, thoracic and mediastinal disorders Sore throat	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	50.0% 1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Renal and urinary disorders Urinary tract obstruction	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Renal and urinary disorders Urine discoloration	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Gastrointestinal disorders Vomiting	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations Weight loss	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.
Investigations White blood cell decreased	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 25 months and 6 days.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 25 months and 6 days.