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A Study of MLN0264 in Participants With Cancer of the Stomach or Gastroesophageal Junction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02202759
Recruitment Status : Terminated (Business Decision, No Safety or Efficacy Concerns)
First Posted : July 29, 2014
Results First Posted : May 15, 2017
Last Update Posted : May 15, 2017
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adenocarcinoma of the Stomach
Gastroesophageal Junction Expressing Guanylyl Cyclase C
Intervention Drug: MLN0264
Enrollment 38
Recruitment Details Participants took part in the study at 24 investigative sites in Belgium, Spain, United Kingdom and the United States from 04 August 2014 to 15 January 2016.
Pre-assignment Details Participants with a diagnosis of metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing Guanylyl Cyclase C (GCC) were enrolled in 1 treatment group, MLN0264 1.8 mg/kg, 30-minute IV infusion, Day 1 of each 21-day cycle.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description 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 14 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, 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 9 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, 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 8 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+.
Period Title: Overall Study
Started 9 15 14
Completed 0 0 0
Not Completed 9 15 14
Reason Not Completed
Study Terminated by Sponsor             3             3             3
Withdrawal by Subject             2             1             1
Reason not Specified             4             11             10
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High) Total
Hide Arm/Group Description 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 14 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, 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 9 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, 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 8 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 of all reporting groups
Overall Number of Baseline Participants 9 15 14 38
Hide Baseline Analysis Population Description
Safety population included all participants who received any amount of MLN0264.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 15 participants 14 participants 38 participants
60.1  (7.70) 62.9  (12.78) 62.9  (7.86) 62.2  (9.89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 15 participants 14 participants 38 participants
Female
1
  11.1%
5
  33.3%
1
   7.1%
7
  18.4%
Male
8
  88.9%
10
  66.7%
13
  92.9%
31
  81.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 15 participants 14 participants 38 participants
Hispanic or Latino 0 0 1 1
Not Hispanic or Latino 9 14 12 35
Not Reported 0 1 1 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 15 participants 14 participants 38 participants
White 9 15 12 36
Black or African American 0 0 1 1
Asian 0 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 15 participants 14 participants 38 participants
Belgium 1 0 1 2
United States 6 8 8 22
United Kingdom 0 2 2 4
Spain 2 5 3 10
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 9 participants 15 participants 14 participants 38 participants
169.7  (7.49) 167.8  (9.85) 171.1  (9.38) 169.4  (9.05)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 9 participants 15 participants 14 participants 38 participants
71.51  (11.253) 71.67  (17.060) 72.75  (12.597) 72.03  (13.913)
Body Surface Area  
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 9 participants 15 participants 14 participants 38 participants
1.832  (0.1683) 1.818  (0.2520) 1.854  (0.2014) 1.835  (0.2113)
1.Primary Outcome
Title Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description 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.
Time Frame Day 21, every other cycle, starting with Cycle 2 until disease progression, death or study closure (up to 17 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 14 13
Measure Type: Number
Unit of Measure: percentage of participants
0 14 0
2.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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. A serious adverse event (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. Relationship of each AE to study drug will be determined by the Investigator.
Time Frame From the first dose through 30 days after the last dose of study medication (Up to 10.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received any amount of MLN0264.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 15 14
Measure Type: Number
Unit of Measure: participants
AEs 8 15 14
SAEs 2 5 0
3.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
Hide Description 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.
Time Frame From the first dose through 30 days after the last dose of study medication (Up to 10.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received any amount of MLN0264.
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description:
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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
Overall Number of Participants Analyzed 38
Measure Type: Number
Unit of Measure: participants
Chemistry 8
Hematology 13
Coagulation 24
Urinalysis 0
4.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Vital Signs Findings
Hide Description 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.
Time Frame Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 10.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received any amount of MLN0264.
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description:
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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
Overall Number of Participants Analyzed 38
Measure Type: Number
Unit of Measure: participants
0
5.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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.
Time Frame Time Frame: 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 16.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 14 13
Median (Full Range)
Unit of Measure: days
40
(38 to 311)
49
(38 to 316)
87
(39 to 427)
6.Secondary Outcome
Title Duration of Response
Hide Description Duration of response is defined as the time in days from the date of first documentation of a confirmed response to the date of first documentation of disease progression. Per RECIST v1.1 for target lesions and assessed by magnetic resonance imaging (MRI) - 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.
Time Frame From first documented response until disease progression (Up to 16.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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 response.
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description:
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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
Overall Number of Participants Analyzed 2
Median (Full Range)
Unit of Measure: days
45.5
(1 to 90)
7.Secondary Outcome
Title Disease Control Rate
Hide Description 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. 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 the Longest Diameter (LD) of target lesions, taking as reference the baseline sum LD and no new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) of target lesions, taking as reference the smallest sum LD since the treatment started and no new lesions. Investigator response is based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Time Frame 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 16.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 14 13
Measure Type: Number
Unit of Measure: percentage of participants
11 36 54
8.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time in days from the date of first study drug administration to the date of death.
Time Frame Until death or 6 months after the last patient completes treatment-whichever occurs first (Up to 17 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Response-evaluable population, all participants with measurable disease who received at least 1 dose of MLN0264 and had at least 1 postbaseline response assessment.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 14 13
Median (Full Range)
Unit of Measure: days
230
(79 to 394)
156
(49 to 505)
206
(24 to 427)
9.Secondary Outcome
Title Cmax: Maximum Observed Serum Concentration for MLN0264
Hide Description Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.
Time Frame 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Cmax was not a pre-specified secondary outcome measure. No data was collected.
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description:
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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title MLN0264 Serum Concentrations
Hide Description Blood samples were collected and sent to a laboratory to be tested for serum concentrations of MLN0264.
Time Frame Cycles 1-3 pre-dose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days post-dose; Cycles 4-9 and 11-14 pre-dose and 10 minutes post-dose; End of Treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable population included all participants who received at least 1 dose of MLN0264 and who had 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.
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description:
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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: μg/mL
Cycle 1 Day 1, Pre-Dose (n=37) 0.0000  (0.00000)
Cycle 1 Day 1, 10 Minutes Post-Dose (n=37) 37.0434  (9.93577)
Cycle 1 Day 1, 4 Hours Post-Dose (n=38) 26.0047  (6.27538)
Cycle 1 Day 3, 48 Hours Post-Dose (n=35) 7.0839  (1.64899)
Cycle 1 Day 4, 72 Hours Post-Dose (n=35) 4.4939  (1.25657)
Cycle 1 Day 8, 168 Hours Post-Dose (n=38) 1.6795  (0.71586)
Cycle 1 Day 15, 336 Hours Post-Dose (n=36) 0.5778  (0.22063)
Cycle 2 Day 1, Pre-Dose (n=36) 0.7466  (2.68737)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=36) 32.1622  (9.61463)
Cycle 2 Day 1, 4 Hours Post-Dose (n=36) 26.0278  (9.43156)
Cycle 2 Day 3, 48 Hours Post-Dose (n=36) 7.7186  (2.04169)
Cycle 2 Day 4, 72 Hours Post-Dose (n=33) 4.9140  (1.05592)
Cycle 2 Day 8, 168 Hours Post-Dose (n=35) 1.7813  (0.49456)
Cycle 2 Day 15, 336 Hours Post-Dose (n=36) 0.6959  (0.27579)
Cycle 3 Day 1, Pre-Dose (n=19) 0.4905  (0.77805)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=19) 31.1505  (8.74114)
Cycle 3 Day 1, 4 Hours Post-Dose (n=19) 25.1787  (5.49543)
Cycle 3 Day 3, 48 Hours Post-Dose (n=14) 6.7360  (1.56940)
Cycle 3 Day 4, 72 Hours Post-Dose (n=15) 5.8887  (3.05461)
Cycle 3 Day 8, 168 Hours Post-Dose (n=18) 1.5078  (0.48401)
Cycle 3 Day 15, 336 Hours Post-Dose (n=18) 0.6807  (0.25869)
Cycle 4 Day 1, Pre-Dose (n=16) 0.3916  (0.16462)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=15) 32.3427  (8.33045)
Cycle 5 Day 1, Pre-Dose (n=7) 0.4757  (0.18995)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=7) 33.9286  (7.14793)
Cycle 6 Day 1, Pre-Dose (n=8) 0.4915  (0.34173)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=8) 30.3850  (7.79913)
Cycle 6 Day 4, 72 Hours Post-Dose (n=7) 5.0676  (1.54862)
Cycle 6 Day 8, 168 Hours Post-Dose (n=6) 1.6910  (0.40781)
Cycle 7 Day 1, Pre-Dose (n=3) 0.5097  (0.20409)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=3) 31.0133  (8.23430)
Cycle 8 Day 1, Pre-Dose (n=3) 0.5677  (0.24180)
Cycle 8 Day 1, 10 Minute Post-Dose (n=3) 31.6467  (8.93229)
Cycle 9 Day 1, Pre-Dose (n=2) 0.9290  (0.49639)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=2) 32.3500  (6.77408)
Cycle 11 Day 1, Pre-Dose (n=1) 0.7760  (0.00000)
Cycle 11 Day 1, 10 Minutes Post-Dose (n=1) 56.8400  (0.00000)
Cycle 12 Day 1, Pre-Dose (n=1) 0.7350  (0.00000)
Cycle 12 Day 1, 10 Minutes Post-Dose (n=1) 49.8800  (0.00000)
Cycle 13 Day 1, Pre-Dose (n=1) 0.8870  (0.00000)
Cycle 13 Day 1, 10 Minutes Post-Dose (n=1) 41.6400  (0.00000)
Cycle 14 Day 1, Pre-Dose (n=1) 1.0260  (0.00000)
Cycle 14 Day 1, 10 Minutes Post-Dose (n=1) 41.9200  (0.00000)
End of Treatment (n=26) 0.3323  (0.21216)
11.Secondary Outcome
Title Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Hide Description Blood samples were collected and sent to a laboratory to be tested for conjugated and unconjugated antibodies.
Time Frame Cycles 1-3 pre-dose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days post-dose; Cycles 4-9 and 11-14 pre-dose and 10 minutes post-dose; End of Treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable population included all participants who received at least 1 dose of MLN0264 and who had 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.
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description:
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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: μg/mL
Cycle 1 Day 1, Pre-Dose (n=37) 0.0000  (0.00000)
Cycle 1 Day 1, 10 Minutes Post-Dose (n=37) 41.8154  (10.05341)
Cycle 1 Day 1, 4 Hours Post-Dose (n=38) 35.7626  (8.46954)
Cycle 1 Day 3, 48 Hours Post-Dose (n=35) 16.0664  (3.26969)
Cycle 1 Day 4, 72 Hours Post-Dose (n=35) 11.7461  (2.60098)
Cycle 1 Day 8, 168 Hours Post-Dose (n=38) 6.1851  (1.73972)
Cycle 1 Day 15, 336 Hours Post-Dose (n=36) 3.3926  (1.00149)
Cycle 2 Day 1, Pre-Dose (n=36) 2.5995  (3.79916)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=35) 43.4749  (9.71796)
Cycle 2 Day 1, 4 Hours Post-Dose (n=36) 35.6691  (10.26134)
Cycle 2 Day 3, 48 Hours Post-Dose (n=36) 18.4167  (4.07769)
Cycle 2 Day 4, 72 Hours Post-Dose (n=33) 13.3398  (3.23987)
Cycle 2 Day 8, 168 Hours Post-Dose (n=35) 7.3613  (1.87974)
Cycle 2 Day 15, 336 Hours Post-Dose (n=36) 4.3511  (1.47322)
Cycle 3 Day 1, Pre-Dose (n=19) 2.5274  (1.54088)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=19) 41.3674  (11.88629)
Cycle 3 Day 1, 4 Hours Post-Dose (n=19) 33.2692  (9.42530)
Cycle 3 Day 3, 48 Hours Post-Dose (n=14) 15.9500  (5.08026)
Cycle 3 Day 4, 72 Hours Post-Dose (n=15) 12.8393  (4.56059)
Cycle 3 Day 8, 168 Hours Post-Dose (n=18) 7.5035  (2.01984)
Cycle 3 Day 15, 336 Hours Post-Dose (n=18) 4.2384  (1.66059)
Cycle 4 Day 1, Pre-Dose (n=16) 2.9082  (1.03729)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=15) 45.4333  (13.84498)
Cycle 5 Day 1, Pre-Dose (n=7) 3.2396  (0.88493)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=7) 43.0629  (7.30566)
Cycle 6 Day 1, Pre-Dose (n=8) 3.0810  (1.29133)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=8) 39.9300  (10.13066)
Cycle 6 Day 4, 72 Hours Post-Dose (n=7) 14.7957  (4.09897)
Cycle 6 Day 8, 168 Hours Post-Dose (n=6) 9.6217  (1.53148)
Cycle 7 Day 1, Pre-Dose (n=3) 3.3417  (1.64015)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=3) 42.1667  (8.75528)
Cycle 8 Day 1, Pre-Dose (n=3) 3.0573  (1.21148)
Cycle 8 Day 1, 10 Minute Post-Dose (n=3) 32.6333  (5.94980)
Cycle 9 Day 1, Pre-Dose (n=2) 3.0440  (0.98429)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=2) 45.8000  (7.04278)
Cycle 11 Day 1, Pre-Dose (n=1) 4.2420  (0.00000)
Cycle 11 Day 1, 10 Minutes Post-Dose (n=1) 44.3000  (0.00000)
Cycle 12 Day 1, Pre-Dose (n=1) 4.1020  (0.00000)
Cycle 12 Day 1, 10 Minutes Post-Dose (n=1) 47.3800  (0.00000)
Cycle 13 Day 1, Pre-Dose (n=1) 4.9900  (0.00000)
Cycle 13 Day 1, 10 Minutes Post-Dose (n=1) 55.2600  (0.00000)
Cycle 14 Day 1, Pre-Dose (n=1) 5.6750  (0.00000)
Cycle 14 Day 1, 10 Minutes Post-Dose (n=1) 61.5000  (0.00000)
End of Treatment (n=26) 2.5393  (1.32302)
12.Secondary Outcome
Title Serum Concentration of Monomethyl Auristatin E (MMAE)
Hide Description Blood samples were collected and sent to a laboratory to be tested for MMAE.
Time Frame Cycles 1-3 pre-dose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days post-dose; Cycles 4-9 and 11-14 pre-dose and 10 minutes post-dose; End of Treatment.
Hide Outcome Measure Data
Hide Analysis Population Description
PK-Evaluable population included all participants who received at least 1 dose of MLN0264 and who had 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.
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description:
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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1 Day 1, Pre-Dose (n=37) 0.000  (0.0000)
Cycle 1 Day 1, 10 Minutes Post-Dose (n=37) 0.473  (0.6503)
Cycle 1 Day 1, 4 Hours Post-Dose (n=38) 2.659  (1.5489)
Cycle 1 Day 3, 48 Hours Post-Dose (n=35) 6.153  (3.2773)
Cycle 1 Day 4, 72 Hours Post-Dose (n=35) 5.856  (3.4519)
Cycle 1 Day 8, 168 Hours Post-Dose (n=38) 2.945  (1.8899)
Cycle 1 Day 15, 336 Hours Post-Dose (n=36) 0.532  (0.6693)
Cycle 2 Day 1, Pre-Dose (n=36) 0.116  (0.1118)
Cycle 2 Day 1, 10 Minutes Post-Dose (n=35) 0.425  (0.2697)
Cycle 2 Day 1, 4 Hours Post-Dose (n=36) 2.665  (1.7137)
Cycle 2 Day 3, 48 Hours Post-Dose (n=36) 6.746  (4.2361)
Cycle 2 Day 4, 72 Hours Post-Dose (n=33) 6.111  (3.6283)
Cycle 2 Day 8, 168 Hours Post-Dose (n=35) 2.898  (2.2974)
Cycle 2 Day 15, 336 Hours Post-Dose (n=36) 0.579  (0.6221)
Cycle 3 Day 1, Pre-Dose (n=19) 0.094  (0.1240)
Cycle 3 Day 1, 10 Minutes Post-Dose (n=18) 0.428  (0.4487)
Cycle 3 Day 1, 4 Hours Post-Dose (n=19) 2.302  (1.8893)
Cycle 3 Day 3, 48 Hours Post-Dose (n=14) 4.493  (2.6877)
Cycle 3 Day 4, 72 Hours Post-Dose (n=15) 3.638  (1.8570)
Cycle 3 Day 8, 168 Hours Post-Dose (n=18) 2.135  (1.7030)
Cycle 3 Day 15, 336 Hours Post-Dose (n=17) 0.342  (0.3637)
Cycle 4 Day 1, Pre-Dose (n=16) 0.081  (0.0865)
Cycle 4 Day 1, 10 Minutes Post-Dose (n=15) 0.304  (0.1781)
Cycle 5 Day 1, Pre-Dose (n=7) 0.084  (0.0331)
Cycle 5 Day 1, 10 Minutes Post-Dose (n=7) 0.278  (0.1325)
Cycle 6 Day 1, Pre-Dose (n=8) 0.093  (0.0654)
Cycle 6 Day 1, 10 Minutes Post-Dose (n=7) 0.322  (0.2232)
Cycle 6 Day 4, 72 Hours Post-Dose (n=7) 6.183  (3.3587)
Cycle 6 Day 8, 168 Hours Post-Dose (n=6) 2.417  (1.6379)
Cycle 7 Day 1, Pre-Dose (n=3) 0.044  (0.0083)
Cycle 7 Day 1, 10 Minutes Post-Dose (n=3) 0.115  (0.0439)
Cycle 8 Day 1, Pre-Dose (n=3) 0.058  (0.0103)
Cycle 8 Day 1, 10 Minute Post-Dose (n=3) 0.132  (0.0425)
Cycle 9 Day 1, Pre-Dose (n=2) 0.021  (0.0291)
Cycle 9 Day 1, 10 Minutes Post-Dose (n=2) 0.158  (0.0721)
Cycle 11 Day 1, Pre-Dose (n=1) 0.093  (0.0000)
Cycle 11 Day 1, 10 Minutes Post-Dose (n=1) 0.186  (0.0000)
Cycle 12 Day 1, Pre-Dose (n=1) 0.087  (0.0000)
Cycle 12 Day 1, 10 Minutes Post-Dose (n=1) 0.167  (0.0000)
Cycle 13 Day 1, Pre-Dose (n=1) 0.074  (0.0000)
Cycle 13 Day 1, 10 Minutes Post-Dose (n=1) 0.132  (0.0000)
Cycle 14 Day 1, Pre-Dose (n=1) 0.081  (0.0000)
Cycle 14 Day 1, 10 Minutes Post-Dose (n=1) 0.165  (0.0000)
End of Treatment (n=25) 0.173  (0.3359)
13.Secondary Outcome
Title Number of Participants With Reduction From Baseline in Tumor Size
Hide Description The number of participants with the best percentage of tumor reduction from baseline in the sum of the diameter was calculated.
Time Frame 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 16.7 months)
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Hide Analysis Population Description
Response-Evaluable Population was defined as all participants with measurable disease who receive at least 1 dose of MLN0264 and have at least 1 postbaseline response assessment.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 14 13
Measure Type: Number
Unit of Measure: participants
1 2 4
14.Secondary Outcome
Title Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC)
Hide Description Analysis of GCC protein expression levels in tumor tissue (fresh biopsy pretreatment and whenever a biopsy is considered medically safe and technically feasible) was performed using a semiquantitative immunohistochemistry (IHC) assay and the total GCC H-Score was determined. 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 was required to obtain archival tumor specimens for GCC expression assessment prior to screening.
Time Frame Approximately 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received any amount of MLN0264.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 15 14
Mean (Full Range)
Unit of Measure: scores on a scale
74.8
(27 to 100)
154.6
(110 to 230)
344.3
(260 to 480)
15.Secondary Outcome
Title Number of Participants With Antitherapeutic Antibodies (ATA)
Hide Description 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.
Time Frame Pre-dose of each 21 day cycle and 30 days after last dose of study medication (Up to 10.7 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participant who received any amount of MLN0264.
Arm/Group Title MLN0264 1.8 mg/kg (GCC Low) MLN0264 1.8 mg/kg (GCC Intermediate) MLN0264 1.8 mg/kg (GCC High)
Hide Arm/Group Description:
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 14 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, 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 9 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, 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 8 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 Number of Participants Analyzed 9 15 14
Measure Type: Number
Unit of Measure: participants
0 3 1
Time Frame From the first dose through 30 days after the last dose of study drug (up to 10.7 Months)
Adverse Event Reporting Description At each visit the investigator documented any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by participant or observed by investigator was recorded, irrespective of relation to study treatment.
 
Arm/Group Title MLN0264 1.8 mg/kg
Hide Arm/Group Description 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 14 cycles). The dose may be decreased, delayed or discontinued in participants who develop treatment-associated nonhematologic and hematologic toxicity to MLN0264.
All-Cause Mortality
MLN0264 1.8 mg/kg
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
MLN0264 1.8 mg/kg
Affected / at Risk (%)
Total   7/38 (18.42%) 
Blood and lymphatic system disorders   
Anaemia  1  1/38 (2.63%) 
Cardiac disorders   
Supraventricular tachycardia  1  1/38 (2.63%) 
Gastrointestinal disorders   
Diarrhoea  1  1/38 (2.63%) 
Dysphagia  1  1/38 (2.63%) 
Upper gastrointestinal hemorrhage  1  1/38 (2.63%) 
Hepatobiliary disorders   
Bile duct obstruction  1  1/38 (2.63%) 
Injury, poisoning and procedural complications   
Hip fracture  1  1/38 (2.63%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Gastric cancer  1 [1]  1/38 (2.63%) 
Tumour hemorrhage  1  1/38 (2.63%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, Version 18.0
[1]
One treatment-emergent death occurred during treatment with MLN0264 with and is not related.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MLN0264 1.8 mg/kg
Affected / at Risk (%)
Total   37/38 (97.37%) 
Blood and lymphatic system disorders   
Anaemia  1  6/38 (15.79%) 
Neutropenia  1  5/38 (13.16%) 
Gastrointestinal disorders   
Abdominal pain  1  4/38 (10.53%) 
Ascites  1  2/38 (5.26%) 
Constipation  1  9/38 (23.68%) 
Diarrhoea  1  6/38 (15.79%) 
Dysphagia  1  3/38 (7.89%) 
Gastrooesophageal reflux disease  1  2/38 (5.26%) 
Nausea  1  20/38 (52.63%) 
Stomatitis  1  3/38 (7.89%) 
Vomiting  1  10/38 (26.32%) 
General disorders   
Asthenia  1  10/38 (26.32%) 
Fatigue  1  12/38 (31.58%) 
Oedema peripheral  1  7/38 (18.42%) 
Pain  1  2/38 (5.26%) 
Pyrexia  1  4/38 (10.53%) 
Infections and infestations   
Urinary tract infection  1  2/38 (5.26%) 
Injury, poisoning and procedural complications   
Fall  1  2/38 (5.26%) 
Investigations   
Blood alkaline phosphatase increased  1  4/38 (10.53%) 
Gamma-glutamyltransferase increased  1  4/38 (10.53%) 
Neutrophil count decreased  1  4/38 (10.53%) 
Weight decreased  1  3/38 (7.89%) 
Metabolism and nutrition disorders   
Decreased appetite  1  11/38 (28.95%) 
Dehydration  1  3/38 (7.89%) 
Hyperglycaemia  1  3/38 (7.89%) 
Hypoalbuminaemia  1  4/38 (10.53%) 
Hypocalcaemia  1  4/38 (10.53%) 
Hypokalaemia  1  2/38 (5.26%) 
Hypomagnesaemia  1  2/38 (5.26%) 
Hyponatraemia  1  2/38 (5.26%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  4/38 (10.53%) 
Musculoskeletal pain  1  3/38 (7.89%) 
Myalgia  1  2/38 (5.26%) 
Pain in extremity  1  4/38 (10.53%) 
Nervous system disorders   
Dizziness  1  2/38 (5.26%) 
Hypoaesthesia  1  2/38 (5.26%) 
Neuropathy peripheral  1  4/38 (10.53%) 
Tremor  1  2/38 (5.26%) 
Psychiatric disorders   
Confusional state  1  2/38 (5.26%) 
Depression  1  2/38 (5.26%) 
Renal and urinary disorders   
Proteinuria  1  2/38 (5.26%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  4/38 (10.53%) 
Orthopnoea  1  2/38 (5.26%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  5/38 (13.16%) 
Vascular disorders   
Deep vein thrombosis  1  2/38 (5.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA, Version 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02202759    
Other Study ID Numbers: C26002
U1111-1155-9023 ( Other Identifier: WHO )
2014-000804-88 ( EudraCT Number )
REec-2014-1176 ( Registry Identifier: REec )
First Submitted: July 7, 2014
First Posted: July 29, 2014
Results First Submitted: January 13, 2017
Results First Posted: May 15, 2017
Last Update Posted: May 15, 2017