Trial Outcomes & Findings for A Study of MLN0264 in Patients With Pancreatic Cancer (NCT NCT02202785)
NCT ID: NCT02202785
Last Updated: 2017-05-15
Results Overview
ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
Day 21, every other cycle, starting with Cycle 2 until disease progression, death or study closure (Up to 16 months)
Results posted on
2017-05-15
Participant Flow
Participants took part in the study at 26 investigative sites in Belgium, Spain, United Kingdom and the United States from 24 September 2014 to 15 January 2016.
Participants with a diagnosis of Pancreatic adenocarcinoma were enrolled in 1 treatment group, MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle.
Participant milestones
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Overall Study
STARTED
|
11
|
15
|
17
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
11
|
15
|
17
|
Reasons for withdrawal
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Overall Study
Study Terminated by Sponsor
|
1
|
6
|
4
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Reason not Specified
|
10
|
7
|
13
|
Baseline Characteristics
A Study of MLN0264 in Patients With Pancreatic Cancer
Baseline characteristics by cohort
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=17 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
63.1 years
STANDARD_DEVIATION 11.20 • n=5 Participants
|
65.5 years
STANDARD_DEVIATION 7.41 • n=7 Participants
|
62.9 years
STANDARD_DEVIATION 10.88 • n=5 Participants
|
63.9 years
STANDARD_DEVIATION 9.74 • n=4 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
9 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
|
Region of Enrollment
Belgium
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
0 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
7 participants
n=5 Participants
|
20 participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
15 participants
n=4 Participants
|
|
Height
|
163.0 cm
STANDARD_DEVIATION 13.20 • n=5 Participants
|
162.1 cm
STANDARD_DEVIATION 9.54 • n=7 Participants
|
170.6 cm
STANDARD_DEVIATION 8.51 • n=5 Participants
|
165.7 cm
STANDARD_DEVIATION 10.76 • n=4 Participants
|
|
Weight
|
60.98 kg
STANDARD_DEVIATION 18.769 • n=5 Participants
|
63.45 kg
STANDARD_DEVIATION 18.465 • n=7 Participants
|
71.20 kg
STANDARD_DEVIATION 17.456 • n=5 Participants
|
65.88 kg
STANDARD_DEVIATION 18.261 • n=4 Participants
|
|
Body Surface Area
|
1.650 m^2
STANDARD_DEVIATION 0.3045 • n=5 Participants
|
1.679 m^2
STANDARD_DEVIATION 0.2761 • n=7 Participants
|
1.827 m^2
STANDARD_DEVIATION 0.2575 • n=5 Participants
|
1.730 m^2
STANDARD_DEVIATION 0.2814 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 21, every other cycle, starting with Cycle 2 until disease progression, death or study closure (Up to 16 months)Population: Response-Evaluable population included all participants with measurable disease who received at least 1 dose of MLN0264 and had at least 1 post-baseline response assessment.
ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=13 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST)
|
0 percentage of participants
|
8 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months)Population: Safety population included all participants who received any amount of MLN0264.
Participants with at least one post-baseline potentially clinically significant serum chemistry, hematology, coagulation or urinalysis result. Clinically significant results are those that were assessed by the investigator to be Grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=43 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Chemistry
|
20 Participants
|
—
|
—
|
|
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Hematology
|
16 Participants
|
—
|
—
|
|
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Coagulation
|
23 Participants
|
—
|
—
|
|
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Urinalysis
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months)Population: Safety population included all participants who received any amount of MLN0264.
Participants with at least one potentially clinically significant post-baseline vital sign finding including measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=43 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Number of Participants With Potentially Clinically Significant Vital Signs Findings
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 13.9 months)Population: Response-Evaluable population included all participants with measurable disease who received at least 1 dose of MLN0264 and had at least 1 post-baseline response assessment.
PFS is defined as the time in days from the date of first study drug administration to the date of first documentation of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=13 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Progression Free Survival (PFS)
|
39 days
Interval 9.0 to 82.0
|
42 days
Interval 21.0 to 218.0
|
41 days
Interval 16.0 to 137.0
|
SECONDARY outcome
Timeframe: From first documented response until disease progression (Up to 16 months)Population: Participants from the Response-Evaluable population, all participants with measurable disease who received at least 1 dose of MLN0264 and had at least 1 post-baseline response assessment, who had a response.
Duration of response is defined as the time from the date of first documentation of a Partial Response or better to the date of first documentation of disease progression or relapse based on investigator assessment using RECIST version 1.1 guidelines. Per RECIST version 1.1 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=1 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Duration of Response
|
103 days
Interval 103.0 to 103.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 13.9 months)Population: Response-Evaluable population included all participants with measurable disease who received at least 1 dose of MLN0264 and had at least 1 post-baseline response assessment.
Disease control rate is defined as the percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) with a minimum of 12 weeks' duration. Investigator response is based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=13 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Disease Control Rate
|
0 percentage of participants
|
23 percentage of participants
|
20 percentage of participants
|
SECONDARY outcome
Timeframe: Until death or 6 months after the last patient completes treatment-whichever occurs first (Up to 16 months)Population: Safety population included all participants who received any amount of MLN0264.
Overall survival is defined as the time in days from the date of first study drug administration to the date of death.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=17 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Overall Survival (OS)
|
162 days
Interval 36.0 to 282.0
|
140 days
Interval 43.0 to 443.0
|
162 days
Interval 49.0 to 435.0
|
SECONDARY outcome
Timeframe: Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.Population: Cmax was not a pre-specified secondary outcome measure. No data was collected.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.Population: PK-Evaluable population included all participants who received at least 1 dose of MLN0264 and who have sufficient MLN0264 concentration-time data to permit reliable estimation of MLN0264 exposure. "n" in the categories is the number of participants with data available at the given time-point.
Blood samples were collected and sent to a laboratory to be tested for MMAE.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=43 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 1 Day 1, Pre-Dose
|
0.000 ng/mL
Standard Deviation 0.0000
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 1 Day 1, 10 Minutes Post-Dose
|
0.296 ng/mL
Standard Deviation 0.1624
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 1 Day 1, 4 Hours Post-Dose
|
2.438 ng/mL
Standard Deviation 1.3015
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 1 Day 3, 48 Hours Post-Dose (n=41)
|
5.205 ng/mL
Standard Deviation 2.8110
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 1 Day 4, 72 Hours Post-Dose (n=39)
|
4.918 ng/mL
Standard Deviation 2.3653
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 1 Day 8, 168 Hours Post-Dose (n=43)
|
2.994 ng/mL
Standard Deviation 2.1173
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 1 Day 15, 336 Hours Post-Dose (n=37)
|
0.580 ng/mL
Standard Deviation 0.5073
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 2 Day 1, Pre-Dose (n=37)
|
0.128 ng/mL
Standard Deviation 0.1304
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=37)
|
0.405 ng/mL
Standard Deviation 0.3351
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 2 Day 1, 4 Hours Post-Dose (n=37)
|
2.665 ng/mL
Standard Deviation 1.6053
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 2 Day 3, 48 Hours Post-Dose (n=34)
|
6.223 ng/mL
Standard Deviation 3.5926
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 2 Day 4, 72 Hours Post-Dose (n=32)
|
5.808 ng/mL
Standard Deviation 3.6296
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 2 Day 8, 168 Hours Post-Dose (n=34)
|
2.789 ng/mL
Standard Deviation 2.0437
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 2 Day 15, 336 Hours Post-Dose (n=28)
|
0.560 ng/mL
Standard Deviation 0.5332
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 3 Day 1, Pre-Dose (n=9)
|
0.145 ng/mL
Standard Deviation 0.1318
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=9)
|
0.395 ng/mL
Standard Deviation 0.3514
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 3 Day 1, 4 Hours Post-Dose (n=9)
|
2.237 ng/mL
Standard Deviation 1.6402
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 3 Day 3, 48 Hours Post-Dose (n=8)
|
6.563 ng/mL
Standard Deviation 5.2034
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 3 Day 4, 72 Hours Post-Dose (n=8)
|
6.563 ng/mL
Standard Deviation 6.2902
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 3 Day 8, 168 Hours Post-Dose (n=7)
|
2.826 ng/mL
Standard Deviation 2.0234
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 3 Day 15, 336 Hours Post-Dose (n=7)
|
1.155 ng/mL
Standard Deviation 1.2808
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 4 Day 1, Pre-Dose (n=7)
|
0.232 ng/mL
Standard Deviation 0.2877
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=7)
|
0.446 ng/mL
Standard Deviation 0.4029
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 5 Day 1, Pre-Dose (n=5)
|
0.090 ng/mL
Standard Deviation 0.0594
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=5)
|
0.249 ng/mL
Standard Deviation 0.1004
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 6 Day 1, Pre-Dose (n=5)
|
0.105 ng/mL
Standard Deviation 0.0469
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=5)
|
0.269 ng/mL
Standard Deviation 0.1037
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 6 Day 4, 72 Hours Post-Dose (n=5)
|
4.234 ng/mL
Standard Deviation 1.3134
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 6 Day 8, 168 Hours Post-Dose (n=5)
|
2.002 ng/mL
Standard Deviation 0.9691
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 7 Day 1, Pre-Dose (n=2)
|
0.125 ng/mL
Standard Deviation 0.0365
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=2)
|
0.277 ng/mL
Standard Deviation 0.0806
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 8 Day 1, Pre-Dose (n=2)
|
0.108 ng/mL
Standard Deviation 0.0288
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 8 Day 1, 10 Minute Post-Dose (n=2)
|
0.257 ng/mL
Standard Deviation 0.0481
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 9 Day 1, Pre-Dose (n=2)
|
0.050 ng/mL
Standard Deviation 0.0179
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=2)
|
0.190 ng/mL
Standard Deviation 0.0361
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 10 Day 1, Pre-Dose (n=1)
|
0.132 ng/mL
Standard Deviation 0.0000
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
Cycle 10 Day 1, 10 Minutes Post-Dose (n=1)
|
0.385 ng/mL
Standard Deviation 0.0000
|
—
|
—
|
|
Serum Concentration of Monomethyl Auristatin E (MMAE)
End of Treatment (n=27)
|
0.137 ng/mL
Standard Deviation 0.1695
|
—
|
—
|
SECONDARY outcome
Timeframe: From pre-screening through end of study (approximately 18 months)Population: Safety population included all participants who received any amount of MLN0264.
GCC H-score is based on the sum of the 0 to 300 H-score for cytoplasmic staining and the 0 to 300 H-score for apical staining for a total possible H-score 0 to 600. Separate consent is required to obtain archival tumor specimens for GCC expression assessment prior to screening.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=17 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC)
|
29.6 scores on a scale
Interval 10.0 to 55.0
|
84.0 scores on a scale
Interval 60.0 to 110.0
|
204.2 scores on a scale
Interval 120.0 to 355.0
|
SECONDARY outcome
Timeframe: From the first dose through 30 days after the last dose of study medication (Up to 7.9 months)Population: Safety population included all participants who received any amount of MLN0264.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=17 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
11 Participants
|
15 Participants
|
17 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
3 Participants
|
7 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.Population: Pharmacokinetic (PK)-Evaluable population included all participants who received at least 1 dose of MLN0264 and who have sufficient MLN0264 concentration-time data to permit reliable estimation of MLN0264 exposure. "n" in the categories is the number of participants with data available at the given time-point.
Blood samples were collected and sent to a laboratory to be tested for serum concentrations of MLN0264.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=43 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
MLN0264 Serum Concentrations
Cycle 1 Day 1, Pre-Dose
|
0.000 μg/mL
Standard Deviation 0.0000
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 1 Day 1, 10 Minutes Post-Dose
|
36.647 μg/mL
Standard Deviation 10.0936
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 1 Day 1, 4 Hours Post-Dose
|
27.898 μg/mL
Standard Deviation 8.4886
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 1 Day 3, 48 Hours Post-Dose (n=41)
|
6.950 μg/mL
Standard Deviation 1.9173
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 1 Day 4, 72 Hours Post-Dose (n=39)
|
4.758 μg/mL
Standard Deviation 1.5349
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 1 Day 8, 168 Hours Post-Dose (n=43)
|
1.563 μg/mL
Standard Deviation 0.5818
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 1 Day 15, 336 Hours Post-Dose (n=37)
|
0.582 μg/mL
Standard Deviation 0.2331
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 2 Day 1, Pre-Dose (n=37)
|
0.261 μg/mL
Standard Deviation 0.1643
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 2 Day 1, 10 Minutes Post-Dose (n=37)
|
30.856 μg/mL
Standard Deviation 9.9483
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 2 Day 1, 4 Hours Post-Dose (n=37)
|
26.691 μg/mL
Standard Deviation 7.9664
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 2 Day 3, 48 Hours Post-Dose (n=35)
|
7.021 μg/mL
Standard Deviation 2.4977
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 2 Day 4, 72 Hours Post-Dose (n=32)
|
4.432 μg/mL
Standard Deviation 1.6115
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 2 Day 8, 168 Hours Post-Dose (n=34)
|
1.681 μg/mL
Standard Deviation 0.7800
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 2 Day 15, 336 Hours Post-Dose (n=27)
|
0.692 μg/mL
Standard Deviation 0.3038
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 3 Day 1, Pre-Dose (n=9)
|
0.431 μg/mL
Standard Deviation 0.1481
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 3 Day 1, 10 Minutes Post-Dose (n=9)
|
34.978 μg/mL
Standard Deviation 5.3350
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 3 Day 1, 4 Hours Post-Dose (n=9)
|
26.393 μg/mL
Standard Deviation 3.3557
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 3 Day 3, 48 Hours Post-Dose (n=8)
|
9.486 μg/mL
Standard Deviation 2.9593
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 3 Day 4, 72 Hours Post-Dose (n=8)
|
6.579 μg/mL
Standard Deviation 1.8102
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 3 Day 8, 168 Hours Post-Dose (n=7)
|
1.701 μg/mL
Standard Deviation 0.4201
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 3 Day 15, 336 Hours Post-Dose (n=7)
|
0.890 μg/mL
Standard Deviation 0.2276
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 4 Day 1, Pre-Dose (n=7)
|
0.490 μg/mL
Standard Deviation 0.1881
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 4 Day 1, 10 Minutes Post-Dose (n=7)
|
37.166 μg/mL
Standard Deviation 9.3823
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 5 Day 1, Pre-Dose (n=5)
|
0.446 μg/mL
Standard Deviation 0.2197
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 5 Day 1, 10 Minutes Post-Dose (n=5)
|
31.060 μg/mL
Standard Deviation 8.3802
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 6 Day 1, Pre-Dose (n=5)
|
0.412 μg/mL
Standard Deviation 0.2183
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 6 Day 1, 10 Minutes Post-Dose (n=5)
|
23.204 μg/mL
Standard Deviation 12.9564
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 6 Day 4, 72 Hours Post-Dose (n=5)
|
4.689 μg/mL
Standard Deviation 0.9286
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 6 Day 8, 168 Hours Post-Dose (n=5)
|
1.410 μg/mL
Standard Deviation 0.2504
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 7 Day 1, Pre-Dose (n=2)
|
0.277 μg/mL
Standard Deviation 0.0863
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 7 Day 1, 10 Minutes Post-Dose (n=2)
|
34.560 μg/mL
Standard Deviation 6.5337
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 8 Day 1, Pre-Dose (n=2)
|
2.047 μg/mL
Standard Deviation 2.6517
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 8 Day 1, 10 Minute Post-Dose (n=2)
|
27.120 μg/mL
Standard Deviation 4.8649
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 9 Day 1, Pre-Dose (n=2)
|
0.178 μg/mL
Standard Deviation 0.0467
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 9 Day 1, 10 Minutes Post-Dose (n=2)
|
31.880 μg/mL
Standard Deviation 0.4808
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 10 Day 1, Pre-Dose (n=1)
|
0.207 μg/mL
Standard Deviation 0.0000
|
—
|
—
|
|
MLN0264 Serum Concentrations
Cycle 10 Day 1, 10 Minutes Post-Dose (n=1)
|
20.860 μg/mL
Standard Deviation 0.0000
|
—
|
—
|
|
MLN0264 Serum Concentrations
End of Treatment (n=27)
|
0.324 μg/mL
Standard Deviation 0.2618
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.Population: PK-Evaluable population included all participants who received at least 1 dose of MLN0264 and who have sufficient MLN0264 concentration-time data to permit reliable estimation of MLN0264 exposure."n" in the categories is the number of participants with data available at the given time-point.
Blood samples were collected and sent to a laboratory to be tested for conjugated and unconjugated antibodies.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=43 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 1 Day 1, Pre-Dose
|
0.000 μg/mL
Standard Deviation 0.0000
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 1 Day 1, 10 Minutes Post-Dose
|
37.599 μg/mL
Standard Deviation 9.4299
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 1 Day 1, 4 Hours Post-Dose
|
32.974 μg/mL
Standard Deviation 8.1824
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 1 Day 3, 48 Hours Post-Dose (n=41)
|
14.051 μg/mL
Standard Deviation 4.0368
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 1 Day 4, 72 Hours Post-Dose (n=39)
|
10.546 μg/mL
Standard Deviation 3.6488
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 1 Day 8, 168 Hours Post-Dose (n=43)
|
5.252 μg/mL
Standard Deviation 1.7703
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 1 Day 15, 336 Hours Post-Dose (n=37)
|
2.958 μg/mL
Standard Deviation 1.1577
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 2 Day 1, Pre-Dose (n=37)
|
1.668 μg/mL
Standard Deviation 0.7608
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=37)
|
35.963 μg/mL
Standard Deviation 10.9226
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 2 Day 1, 4 Hours Post-Dose (n=37)
|
32.134 μg/mL
Standard Deviation 9.7822
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 2 Day 3, 48 Hours Post-Dose (n=35)
|
14.194 μg/mL
Standard Deviation 4.8398
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 2 Day 4, 72 Hours Post-Dose (n=32)
|
10.948 μg/mL
Standard Deviation 4.2741
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 2 Day 8, 168 Hours Post-Dose (n=34)
|
6.312 μg/mL
Standard Deviation 2.7008
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 2 Day 15, 336 Hours Post-Dose (n=27)
|
3.923 μg/mL
Standard Deviation 1.7465
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 3 Day 1, Pre-Dose (n=9)
|
2.654 μg/mL
Standard Deviation 1.0757
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=9)
|
39.500 μg/mL
Standard Deviation 6.0580
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 3 Day 1, 4 Hours Post-Dose (n=9)
|
37.549 μg/mL
Standard Deviation 8.2628
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 3 Day 3, 48 Hours Post-Dose (n=8)
|
19.181 μg/mL
Standard Deviation 3.7260
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 3 Day 4, 72 Hours Post-Dose (n=8)
|
15.808 μg/mL
Standard Deviation 2.0102
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 3 Day 8, 168 Hours Post-Dose (n=7)
|
6.631 μg/mL
Standard Deviation 3.8091
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 3 Day 15, 336 Hours Post-Dose (n=7)
|
5.279 μg/mL
Standard Deviation 1.9171
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 4 Day 1, Pre-Dose (n=7)
|
3.252 μg/mL
Standard Deviation 1.3859
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=7)
|
42.194 μg/mL
Standard Deviation 8.8085
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 5 Day 1, Pre-Dose (n=5)
|
2.734 μg/mL
Standard Deviation 1.2045
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=5)
|
44.244 μg/mL
Standard Deviation 27.1286
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 6 Day 1, Pre-Dose (n=5)
|
2.854 μg/mL
Standard Deviation 1.7255
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=5)
|
36.304 μg/mL
Standard Deviation 12.1646
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 6 Day 4, 72 Hours Post-Dose (n=5)
|
12.667 μg/mL
Standard Deviation 3.4384
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 6 Day 8, 168 Hours Post-Dose (n=5)
|
8.040 μg/mL
Standard Deviation 3.1264
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 7 Day 1, Pre-Dose (n=2)
|
1.997 μg/mL
Standard Deviation 0.7877
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=2)
|
37.130 μg/mL
Standard Deviation 4.9922
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 8 Day 1, Pre-Dose (n=2)
|
1.901 μg/mL
Standard Deviation 0.5834
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 8 Day 1, 10 Minute Post-Dose (n=2)
|
66.240 μg/mL
Standard Deviation 43.7558
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 9 Day 1, Pre-Dose (n=2)
|
1.462 μg/mL
Standard Deviation 0.4547
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=2)
|
34.790 μg/mL
Standard Deviation 2.0789
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 10 Day 1, Pre-Dose (n=1)
|
1.282 μg/mL
Standard Deviation 0.0000
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Cycle 10 Day 1, 10 Minutes Post-Dose (n=1)
|
26.320 μg/mL
Standard Deviation 0.0000
|
—
|
—
|
|
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
End of Treatment (n=27)
|
2.000 μg/mL
Standard Deviation 1.2480
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 21 of each 21-day cycle, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Approximately 13.9 months)Population: Response-Evaluable Population was defined as all participants with measurable disease who receive at least 1 dose of MLN0264 and have at least 1 post-baseline response assessment.
The percentage of participants with the best percentage of tumor reduction from baseline in the sum of the diameter was calculated
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=10 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Percentage of Participants With Reduction From Baseline in Tumor Size
|
50 percentage of participants
|
64 percentage of participants
|
73 percentage of participants
|
SECONDARY outcome
Timeframe: Pre-dose of each 21 day cycle and 30 days after last dose of study medication (Up to 7.9 months)Population: Safety Population included all participant who received any amount of MLN0264.
Blood samples were collected to assess the immunogenicity of MLN0264 (ATA development) using a laboratory test. Neutralizing ATA assessment was performed for ATA-positive samples only.
Outcome measures
| Measure |
MLN0264 1.8 mg/kg (GCC Low)
n=11 Participants
MLN0264 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 4 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Low (combined H-score 10-59). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC Intermediate)
n=15 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score 60-119). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
MLN0264 1.8 mg/kg (GCC High)
n=17 Participants
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 6 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264. Participants with guanylyl cyclase C (GCC) protein expression=Intermediate (combined H-score \>120). Total H-score 0-600 is the combined score of cytoplasmic staining 0-300 and apical staining 0-300 and is based on the percentage of tumor cells with staining intensity 1+, 2+ and 3+.
|
|---|---|---|---|
|
Number of Participants With Antitherapeutic Antibodies (ATA)
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
MLN0264 1.8 mg/kg
Serious events: 19 serious events
Other events: 42 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MLN0264 1.8 mg/kg
n=43 participants at risk
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
|
|---|---|
|
Gastrointestinal disorders
Intestinal obstruction
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
4.7%
2/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Ascites
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Hepatobiliary disorders
Cholangitis
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Hepatobiliary disorders
Hepatic failure
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Hepatobiliary disorders
Bile duct obstruction
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.7%
2/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Device failure
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
General physical health deterioration
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Infections and infestations
Candida sepsis
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Infections and infestations
Escherichia infection
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Infections and infestations
Biliary tract infection
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Cerebral ischaemia
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Presyncope
|
2.3%
1/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Other adverse events
| Measure |
MLN0264 1.8 mg/kg
n=43 participants at risk
MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle, for up to 1 year or until disease progression or unacceptable toxicity occurs (Up to 10 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
14.0%
6/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
23.3%
10/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Abdominal distension
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
44.2%
19/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Constipation
|
32.6%
14/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
11.6%
5/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Dry mouth
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.6%
5/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Nausea
|
39.5%
17/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
25.6%
11/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Asthenia
|
20.9%
9/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Fatigue
|
37.2%
16/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Oedema peripheral
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Pain
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Pyrexia
|
14.0%
6/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Infections and infestations
Urinary tract infection
|
11.6%
5/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Blood alkaline phosphatase increased
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Weight decreased
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
30.2%
13/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Dehydration
|
16.3%
7/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
11.6%
5/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.3%
7/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Headache
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Neuropathy peripheral
|
11.6%
5/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Psychiatric disorders
Anxiety
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Psychiatric disorders
Insomnia
|
9.3%
4/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Renal and urinary disorders
Dysuria
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.6%
5/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
14.0%
6/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Vascular disorders
Hypertension
|
7.0%
3/43 • From the first dose through 30 days after the last dose of study drug (Up to 7.9 Months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
- Publication restrictions are in place
Restriction type: OTHER