Pancreatic Adenocarcinoma
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to assess the efficacy, safety and tolerability of MLN0264 in patients with advanced or metastatic guanylyl cyclase C (GCC)-positive adenocarcinoma of the pancreas.
Detailed description
The drug being tested in this study is called MLN0264. MLN0264 is being tested to treat tumors in people who have metastatic adenocarcinoma of the pancreas expressing guanylyl cyclase C (GCC). This study will assess tumor size reduction in patients who are administered MLN0264. The study will enroll 42 to 81 patients. All participants will be administered MLN0264 at 1.8 mg/kg as a single, 30-minute, intravenous (IV) infusion on Day 1 of each 3-week treatment cycle, followed by a rest period of 20 days. Participants will continue to receive MLN0264 for up to 1 year or until disease progression or unacceptable toxicity occurs. This multi-centre trial will be conducted worldwide. The overall time to participate in this study is approximately 19 months. Participants will make 3 to 6 visits to the clinic per treatment cycle, an end-of-treatment visit will occur 30 days after the last dose of study medication, and follow-up assessments will occur every 12 weeks until death or 6 months after the last patient completes treatment - whichever occurs first.
Interventions
DRUGMLN0264
MLN0264 IV infusion
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants 18 years of age or older when written informed consent is obtained. 2. Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the pancreas with immunohistochemistry (IHC) evidence of guanylyl cyclase C (GCC) expression indicated by an H-score of 10 or greater. 3. Treatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the pancreas. 4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. All scans and x-rays used to document measurable disease must be done within 28 days before enrollment (ascites and bone lesions are not considered measureable disease). 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before enrollment. 6. Female participants who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.) 7. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care. 8. Adequate organ and hematological function as evidenced by the following laboratory values within 14 days before enrollment: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hemoglobin ≥ 9 g/dL * Activated partial thromboplastin time (aPTT) ≤ 1.5 x the upper limit of the normal range (ULN) per institutional laboratory normal range * International normalized ratio (INR) ≤ 1.5 x ULN * Serum creatinine ≤ 1.5 x ULN * Total bilirubin ≤ 1.5 x ULN * Albumin ≥ 3g/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN * Serum lipase ≤ 3 x ULN and serum amylase within the normal range 9. Resolution of all toxic effects of prior treatments except alopecia to Grade 0 or 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. 10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion criteria
1. Radiotherapy within 4 weeks before enrollment. 2. Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent or chemotherapy. 3. Female participants who are lactating and breastfeeding or have a positive pregnancy test during the Screening period. 4. Uncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months before enrollment, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication. 5. Treatment with any medication that has a clinically relevant potential risk of prolonging the QT interval or inducing torsades de pointes that cannot be discontinued or switched to a different medication before starting study drug. 6. Participants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc). 7. Ongoing or clinically significant active infection as judged by the investigator. 8. Signs of peripheral neuropathy (PN) ≥ NCI CTCAE Grade 2. 9. Concomitant chemotherapy, hormonal therapy, immunotherapy, or any other form of cancer treatment. 10. Use of strong cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks before the first dose of study drug. 11. Any preexisting medical condition of sufficient severity to prevent full compliance with the study. 12. History of or current neoplasm other than gastric adenocarcinoma, except for curatively treated nonmelanoma skin cancer or in situ carcinoma of the cervix uteri. 13. Known diagnosis of human immunodeficiency virus (HIV) infection (testing is not mandatory). 14. Symptomatic brain metastases. 15. Ongoing anticoagulant therapy (eg, aspirin, coumadin, heparin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) | Day 21, every other cycle, starting with Cycle 2 until disease progression, death or study closure (Up to 16 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Potentially Clinically Significant Vital Signs Findings | Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months) | 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. |
| Progression Free Survival (PFS) | 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) | 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. |
| Duration of Response | From first documented response until disease progression (Up to 16 months) | 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. |
| Disease Control Rate | 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) | 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. |
| Overall Survival (OS) | Until death or 6 months after the last patient completes treatment-whichever occurs first (Up to 16 months) | Overall survival is defined as the time in days from the date of first study drug administration to the date of death. |
| Cmax: Maximum Observed Serum Concentration for MLN0264 | 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. | — |
| Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 7.9 months) | 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. |
| Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC) | From pre-screening through end of study (approximately 18 months) | 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. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the first dose through 30 days after the last dose of study medication (Up to 7.9 months) | 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. |
| MLN0264 Serum Concentrations | 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. | Blood samples were collected and sent to a laboratory to be tested for serum concentrations of MLN0264. |
| Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | 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. | Blood samples were collected and sent to a laboratory to be tested for conjugated and unconjugated antibodies. |
| Percentage of Participants With Reduction From Baseline in Tumor Size | 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) | The percentage of participants with the best percentage of tumor reduction from baseline in the sum of the diameter was calculated |
| Number of Participants With Antitherapeutic Antibodies (ATA) | Pre-dose of each 21 day cycle and 30 days after last dose of study medication (Up to 7.9 months) | 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. |
| Serum Concentration of Monomethyl Auristatin E (MMAE) | 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. | Blood samples were collected and sent to a laboratory to be tested for MMAE. |
Countries
Belgium, Spain, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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+. | 11 |
| 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+. | 15 |
| 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+. | 17 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Reason not Specified | 10 | 7 | 13 |
| Overall Study | Study Terminated by Sponsor | 1 | 6 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | MLN0264 1.8 mg/kg (GCC Intermediate) | Total | MLN0264 1.8 mg/kg (GCC Low) | MLN0264 1.8 mg/kg (GCC High) |
|---|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 7.41 | 63.9 years STANDARD_DEVIATION 9.74 | 63.1 years STANDARD_DEVIATION 11.2 | 62.9 years STANDARD_DEVIATION 10.88 |
| Body Surface Area | 1.679 m^2 STANDARD_DEVIATION 0.2761 | 1.730 m^2 STANDARD_DEVIATION 0.2814 | 1.650 m^2 STANDARD_DEVIATION 0.3045 | 1.827 m^2 STANDARD_DEVIATION 0.2575 |
| Height | 162.1 cm STANDARD_DEVIATION 9.54 | 165.7 cm STANDARD_DEVIATION 10.76 | 163.0 cm STANDARD_DEVIATION 13.2 | 170.6 cm STANDARD_DEVIATION 8.51 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 14 Participants | 39 Participants | 8 Participants | 17 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 41 Participants | 9 Participants | 17 Participants |
| Region of Enrollment Belgium | 4 participants | 5 participants | 1 participants | 0 participants |
| Region of Enrollment Spain | 4 participants | 15 participants | 2 participants | 9 participants |
| Region of Enrollment United Kingdom | 1 participants | 3 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 6 participants | 20 participants | 7 participants | 7 participants |
| Sex: Female, Male Female | 11 Participants | 23 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 20 Participants | 3 Participants | 13 Participants |
| Weight | 63.45 kg STANDARD_DEVIATION 18.465 | 65.88 kg STANDARD_DEVIATION 18.261 | 60.98 kg STANDARD_DEVIATION 18.769 | 71.20 kg STANDARD_DEVIATION 17.456 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 43 |
| serious Total, serious adverse events | 19 / 43 |
Outcome results
Primary
Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST)
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 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) | 0 percentage of participants |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) | 8 percentage of participants |
| MLN0264 1.8 mg/kg (GCC High) | Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) | 0 percentage of participants |
Secondary
Cmax: Maximum Observed Serum Concentration for MLN0264
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.
Population: Cmax was not a pre-specified secondary outcome measure. No data was collected.
Secondary
Disease Control Rate
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.
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 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Disease Control Rate | 0 percentage of participants |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Disease Control Rate | 23 percentage of participants |
| MLN0264 1.8 mg/kg (GCC High) | Disease Control Rate | 20 percentage of participants |
Secondary
Duration of 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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Duration of Response | 103 days |
Secondary
Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC)
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.
Time frame: From pre-screening through end of study (approximately 18 months)
Population: Safety population included all participants who received any amount of MLN0264.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC) | 29.6 scores on a scale |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC) | 84.0 scores on a scale |
| MLN0264 1.8 mg/kg (GCC High) | Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC) | 204.2 scores on a scale |
Secondary
MLN0264 Serum Concentrations
Blood samples were collected and sent to a laboratory to be tested for serum concentrations of MLN0264.
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.
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 1 Day 1, Pre-Dose | 0.000 μg/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 1 Day 1, 10 Minutes Post-Dose | 36.647 μg/mL | Standard Deviation 10.0936 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 1 Day 1, 4 Hours Post-Dose | 27.898 μg/mL | Standard Deviation 8.4886 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 1 Day 3, 48 Hours Post-Dose (n=41) | 6.950 μg/mL | Standard Deviation 1.9173 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 1 Day 4, 72 Hours Post-Dose (n=39) | 4.758 μg/mL | Standard Deviation 1.5349 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 1 Day 8, 168 Hours Post-Dose (n=43) | 1.563 μg/mL | Standard Deviation 0.5818 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 1 Day 15, 336 Hours Post-Dose (n=37) | 0.582 μg/mL | Standard Deviation 0.2331 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 2 Day 1, Pre-Dose (n=37) | 0.261 μg/mL | Standard Deviation 0.1643 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 2 Day 1, 10 Minutes Post-Dose (n=37) | 30.856 μg/mL | Standard Deviation 9.9483 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 2 Day 1, 4 Hours Post-Dose (n=37) | 26.691 μg/mL | Standard Deviation 7.9664 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 2 Day 3, 48 Hours Post-Dose (n=35) | 7.021 μg/mL | Standard Deviation 2.4977 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 2 Day 4, 72 Hours Post-Dose (n=32) | 4.432 μg/mL | Standard Deviation 1.6115 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 2 Day 8, 168 Hours Post-Dose (n=34) | 1.681 μg/mL | Standard Deviation 0.78 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 2 Day 15, 336 Hours Post-Dose (n=27) | 0.692 μg/mL | Standard Deviation 0.3038 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 3 Day 1, Pre-Dose (n=9) | 0.431 μg/mL | Standard Deviation 0.1481 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 3 Day 1, 10 Minutes Post-Dose (n=9) | 34.978 μg/mL | Standard Deviation 5.335 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 3 Day 1, 4 Hours Post-Dose (n=9) | 26.393 μg/mL | Standard Deviation 3.3557 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 3 Day 3, 48 Hours Post-Dose (n=8) | 9.486 μg/mL | Standard Deviation 2.9593 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 3 Day 4, 72 Hours Post-Dose (n=8) | 6.579 μg/mL | Standard Deviation 1.8102 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 3 Day 8, 168 Hours Post-Dose (n=7) | 1.701 μg/mL | Standard Deviation 0.4201 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 3 Day 15, 336 Hours Post-Dose (n=7) | 0.890 μg/mL | Standard Deviation 0.2276 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 4 Day 1, Pre-Dose (n=7) | 0.490 μg/mL | Standard Deviation 0.1881 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 4 Day 1, 10 Minutes Post-Dose (n=7) | 37.166 μg/mL | Standard Deviation 9.3823 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 5 Day 1, Pre-Dose (n=5) | 0.446 μg/mL | Standard Deviation 0.2197 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 5 Day 1, 10 Minutes Post-Dose (n=5) | 31.060 μg/mL | Standard Deviation 8.3802 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 6 Day 1, Pre-Dose (n=5) | 0.412 μg/mL | Standard Deviation 0.2183 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 6 Day 1, 10 Minutes Post-Dose (n=5) | 23.204 μg/mL | Standard Deviation 12.9564 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 6 Day 4, 72 Hours Post-Dose (n=5) | 4.689 μg/mL | Standard Deviation 0.9286 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 6 Day 8, 168 Hours Post-Dose (n=5) | 1.410 μg/mL | Standard Deviation 0.2504 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 7 Day 1, Pre-Dose (n=2) | 0.277 μg/mL | Standard Deviation 0.0863 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 7 Day 1, 10 Minutes Post-Dose (n=2) | 34.560 μg/mL | Standard Deviation 6.5337 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 8 Day 1, Pre-Dose (n=2) | 2.047 μg/mL | Standard Deviation 2.6517 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 8 Day 1, 10 Minute Post-Dose (n=2) | 27.120 μg/mL | Standard Deviation 4.8649 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 9 Day 1, Pre-Dose (n=2) | 0.178 μg/mL | Standard Deviation 0.0467 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 9 Day 1, 10 Minutes Post-Dose (n=2) | 31.880 μg/mL | Standard Deviation 0.4808 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 10 Day 1, Pre-Dose (n=1) | 0.207 μg/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | Cycle 10 Day 1, 10 Minutes Post-Dose (n=1) | 20.860 μg/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | MLN0264 Serum Concentrations | End of Treatment (n=27) | 0.324 μg/mL | Standard Deviation 0.2618 |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 11 Participants |
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 Participants |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 15 Participants |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 7 Participants |
| MLN0264 1.8 mg/kg (GCC High) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 17 Participants |
| MLN0264 1.8 mg/kg (GCC High) | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 9 Participants |
Secondary
Number of Participants With Antitherapeutic Antibodies (ATA)
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 7.9 months)
Population: Safety Population included all participant who received any amount of MLN0264.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Antitherapeutic Antibodies (ATA) | 0 Participants |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Number of Participants With Antitherapeutic Antibodies (ATA) | 0 Participants |
| MLN0264 1.8 mg/kg (GCC High) | Number of Participants With Antitherapeutic Antibodies (ATA) | 0 Participants |
Secondary
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings
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: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Chemistry | 20 Participants |
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Hematology | 16 Participants |
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Coagulation | 23 Participants |
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings | Urinalysis | 0 Participants |
Secondary
Number of Participants With Potentially Clinically Significant Vital Signs Findings
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 7.9 months)
Population: Safety population included all participants who received any amount of MLN0264.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Number of Participants With Potentially Clinically Significant Vital Signs Findings | 0 Participants |
Secondary
Overall Survival (OS)
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 16 months)
Population: Safety population included all participants who received any amount of MLN0264.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Overall Survival (OS) | 162 days |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Overall Survival (OS) | 140 days |
| MLN0264 1.8 mg/kg (GCC High) | Overall Survival (OS) | 162 days |
Secondary
Percentage of Participants With Reduction From Baseline in Tumor Size
The percentage of participants with the best percentage of tumor reduction from baseline in the sum of the diameter was calculated
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Percentage of Participants With Reduction From Baseline in Tumor Size | 50 percentage of participants |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Percentage of Participants With Reduction From Baseline in Tumor Size | 64 percentage of participants |
| MLN0264 1.8 mg/kg (GCC High) | Percentage of Participants With Reduction From Baseline in Tumor Size | 73 percentage of participants |
Secondary
Progression Free Survival (PFS)
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: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Progression Free Survival (PFS) | 39 days |
| MLN0264 1.8 mg/kg (GCC Intermediate) | Progression Free Survival (PFS) | 42 days |
| MLN0264 1.8 mg/kg (GCC High) | Progression Free Survival (PFS) | 41 days |
Secondary
Serum Concentration of Monomethyl Auristatin E (MMAE)
Blood samples were collected and sent to a laboratory to be tested for MMAE.
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.
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 1 Day 1, Pre-Dose | 0.000 ng/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 1 Day 1, 10 Minutes Post-Dose | 0.296 ng/mL | Standard Deviation 0.1624 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 1 Day 1, 4 Hours Post-Dose | 2.438 ng/mL | Standard Deviation 1.3015 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 1 Day 3, 48 Hours Post-Dose (n=41) | 5.205 ng/mL | Standard Deviation 2.811 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 2 Day 1, Pre-Dose (n=37) | 0.128 ng/mL | Standard Deviation 0.1304 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 3 Day 1, Pre-Dose (n=9) | 0.145 ng/mL | Standard Deviation 0.1318 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 4 Day 1, Pre-Dose (n=7) | 0.232 ng/mL | Standard Deviation 0.2877 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 5 Day 1, Pre-Dose (n=5) | 0.090 ng/mL | Standard Deviation 0.0594 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 6 Day 1, Pre-Dose (n=5) | 0.105 ng/mL | Standard Deviation 0.0469 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 7 Day 1, Pre-Dose (n=2) | 0.125 ng/mL | Standard Deviation 0.0365 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 8 Day 1, Pre-Dose (n=2) | 0.108 ng/mL | Standard Deviation 0.0288 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 9 Day 1, Pre-Dose (n=2) | 0.050 ng/mL | Standard Deviation 0.0179 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 10 Day 1, Pre-Dose (n=1) | 0.132 ng/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | Cycle 10 Day 1, 10 Minutes Post-Dose (n=1) | 0.385 ng/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Monomethyl Auristatin E (MMAE) | End of Treatment (n=27) | 0.137 ng/mL | Standard Deviation 0.1695 |
Secondary
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Blood samples were collected and sent to a laboratory to be tested for conjugated and unconjugated antibodies.
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.
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 1, Pre-Dose | 0.000 μg/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 1, 10 Minutes Post-Dose | 37.599 μg/mL | Standard Deviation 9.4299 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 1 Day 1, 4 Hours Post-Dose | 32.974 μg/mL | Standard Deviation 8.1824 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 2 Day 1, Pre-Dose (n=37) | 1.668 μg/mL | Standard Deviation 0.7608 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 3 Day 1, Pre-Dose (n=9) | 2.654 μg/mL | Standard Deviation 1.0757 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 3 Day 1, 10 Minutes Post-Dose (n=9) | 39.500 μg/mL | Standard Deviation 6.058 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 3 Day 3, 48 Hours Post-Dose (n=8) | 19.181 μg/mL | Standard Deviation 3.726 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 4 Day 1, Pre-Dose (n=7) | 3.252 μg/mL | Standard Deviation 1.3859 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 5 Day 1, Pre-Dose (n=5) | 2.734 μg/mL | Standard Deviation 1.2045 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 6 Day 1, Pre-Dose (n=5) | 2.854 μg/mL | Standard Deviation 1.7255 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 7 Day 1, Pre-Dose (n=2) | 1.997 μg/mL | Standard Deviation 0.7877 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 8 Day 1, Pre-Dose (n=2) | 1.901 μg/mL | Standard Deviation 0.5834 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 9 Day 1, Pre-Dose (n=2) | 1.462 μg/mL | Standard Deviation 0.4547 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | Cycle 10 Day 1, Pre-Dose (n=1) | 1.282 μg/mL | Standard Deviation 0 |
| MLN0264 1.8 mg/kg (GCC Low) | 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 |
| MLN0264 1.8 mg/kg (GCC Low) | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) | End of Treatment (n=27) | 2.000 μg/mL | Standard Deviation 1.248 |