Advanced Gastrointestinal Carcinoma, Gastroesophageal Junction Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Recurrent Gastric Adenocarcinoma, Recurrent Gastroesophageal Junction Adenocarcinoma, Recurrent Gastrointestinal Carcinoma
Conditions
Keywords
MLN0264, Advanced gastrointestinal carcinoma
Brief summary
The purpose of this study is to evaluate the effects of MLN0264 in previously treated Asian participants with Advanced Gastrointestinal (GI) Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2) Expressing Guanylyl Cyclase C (GCC).
Detailed description
The drug being tested in this study is called MLN0264. This drug is being evaluated to check the effects on previously treated Asian individuals with Advanced GI Carcinoma (Phase 1) or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma (Phase 2). The study will enroll approximately 95 participants. In Phase 1, approximately 14 Asian participants with GI malignancies will be enrolled in 3 planned dose cohorts according to the traditional 3 + 3 dose escalation scheme. The starting dose will be 1.2 mg/kg of MLN0264 administered IV on Day 1 of 3-week cycles for up to 1 year or until disease progression or unacceptable toxicity occurs. Dose escalation will take place until Phase 2 recommended dose is determined. In Phase 2, eligible Asian participants with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction will be enrolled. Participants must have failed at least 2 lines of prior anticancer therapy for advanced or metastatic disease. Disease recurrence within 6 months of the last dose of post-surgical adjuvant chemotherapy counts as 1 line of prior anticancer therapy for advanced disease. This multi-center trial will be conducted in Japan, Korea and Taiwan. The overall time to participate in this study is up to 3 years.
Interventions
DRUGMLN0264
MLN0264 IV.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has Diagnosis of GI carcinoma with Immunohistochemistry/ Immunohistochemical (IHC) evidence of expression of GCC protein (H-score of 10 or greater), for which standard treatment is no longer effective or does not offer curative or life-prolonging potential. * Has completed prior chemotherapy, immunotherapy or radiation therapy at least 4 weeks prior to enrollment (except for Avastin \[bevacizumab\] for which at least 8 weeks from its last administration should elapse prior to enrollment). * Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the stomach or gastroesophageal junction with IHC evidence of expression of GCC indicated by an H-score of 10 or greater. * Has completed prior chemotherapy, immunotherapy or radiation therapy at least 4 weeks prior to enrollment. * Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. * Has Eastern Cooperative Oncology Group performance status of 0 or 1 (within 14 days prior to enrollment). * Females must be 1-year postmenopausal, or even if surgically sterile, agree to use other acceptable forms of birth control. * Has adequate organ and hematological function. * Has 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
Exclusion criteria
* Has Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent. * Female participants who are in the lactation period, even if they discontinue breastfeeding, or have a positive pregnancy test during the Screening period. * Has uncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months prior to enrollment. * Has 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 prior to starting study drug. * Participants with electrocardiogram (ECG) abnormalities considered by the investigator to be clinically -significant, or repeated baseline prolongation of the rate-corrected QT interval millisecond (msec) of electrocardiograph (QTc). * Ongoing or clinically significant active infection. * Has signs of peripheral neuropathy. * Concomitant chemotherapy, hormonal therapy, immunotherapy, or any other form of cancer treatment. * Use of strong cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks before the first dose of study drug. * Has any preexisting medical condition of sufficient severity to prevent full compliance with the study. * Has past or concurrent history of neoplasm other than GI carcinoma (phase 1) or gastric adenocarcinoma (phase 2), except for curatively treated nonmelanoma skin cancer or in situ carcinoma of the cervix uteri. * Known diagnosis of human immunodeficiency virus (HIV) infection. * Has asymptomatic brain metastases. * Has an alcohol or substance abuse disorder. * Has positive test for hepatitis B surface antigen. * History of hypersensitivity to any ingredient of MLN0264.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2- Overall Response Rate | Baseline until end of study treatment (approximately 1 year) | ORR is the percentage of participants with complete response \[CR\] + partial response \[PR\]) based on modified Response Evaluation Criteria in Solid Tumors (RECIST). Overall response rate (CR + PR) based on modified RECIST version 1.1 guidelines. CR: Disappearance of all target lesions and PR: at least a 30 percentage (%) decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total representative of all involved organs were identified as target lesions at baseline. Target lesions were selected on the basis of size (longest lesions) and suitability for reproducible repeated measurements. |
| Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MMAE | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | Phase 1: Baseline through 30 days after the last dose of study drug (approximately up to 35 weeks) | — |
| Phase 1- Number of Participants Reporting One or More Serious Adverse Events (SAE) | Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks) | — |
| Phase 1- Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | Phase 1: Up to Cycle 1 (3 weeks) | Toxicity evaluated as per NationalCancerInstituteCommonTerminologyCriteria for AEs (NCI CTCAE),version 4.03.DLT=any event related to MLN0264:Grade 4 neutropenia(absolute neutrophil count\[ANC\]less than\[\<\]500 cells/millimeter\[mm\]\^3); \>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle greater than (\>)2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy. |
| Phase 1- Number of Participants With Markedly Abnormal Laboratory Values | Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks) | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Laboratory assessment includes serum chemistry, hematology, urine analysis and coagulation. |
| Phase 1- Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks) | Vital signs include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (beats per minute \[bpm\]). |
| Phase 1- Recommended Phase 2 Dose (RP2D) | Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks) | RP2D is maximum tolerated dose(MTD) in study Phase1.MTD was highest dose of MLN0264 given at which \<=1 of 6 participants experienced DLTduring Cycle1 of Phase1.DLT=any event related to MLN0264:Grade 4 neutropenia ANC less than\<500 cells mm\^3;\>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle\>2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy. |
| Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264 | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264 | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264 | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264 | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264 | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264 | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Cmax: Maximum Observed Serum Concentration for TAb | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb | Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose | — |
| Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb | Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1- Disease Response Based on the Investigator's Assessment | Phase 1: Day 21 of every other cycle (Cycle 2, 4, 6, 8) up to End of treatment (EOT) (Cycle10 or week 30) | Disease response was based on the investigator's assessment using the modified RECIST version 1.1 guidelines. Evaluation of target lesions included CR (Disappearance of all target lesions),PR(at least a 30% decrease in the sum of the LD of target lesions),Progressive disease (PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions) and Stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD).Evaluation of Non target Lesions included CR (disappearance of all non target lesions and normalization of tumor marker level), Incomplete response/SD (Persistence of 1 or more non target lesions and/or maintenance of tumor marker level above the normal limits) and PD(Appearance of 1 or more new lesions and/or unequivocal progression of existing non target lesions). |
| Phase 2- Percentage of Participants Who Experience at Least One TEAE | Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year) | — |
| Phase 2- Percentage of Participants Who Experience at Least One SAE | Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year) | — |
| Phase 2- Number of Participants With Markedly Abnormal Laboratory Values | Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year) | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Laboratory assessment includes serum chemistry, hematology, urine analysis and coagulation. |
| Phase 2- Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year) | Vital signs include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (beats per minute \[bpm\]). |
| Phase 2- Progression-free Survival (PFS) | Baseline up to EOT, thereafter every 12 weeks until the occurrence of PD, the start of subsequent antineoplastic therapy, or 6 months after discontinuation from treatment, whichever occurs first (total duration of assessment up to 1.5 years) | PFS is defined as the time from the date of first study drug administration to the date of first documentation of progressive disease or death. For a participant who has not progressed and is last known to be alive, PFS was censored at the last response assessment that was stable disease or better. PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions. |
| Phase 2- Duration of Response (DOR) | Day 21 of every other cycle (Cycle 2, 4, 6, 8) up to EOT (approximately 1 year) | DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documentation of Progressive Disease (PD). Responders without documentation of PD were censored at the last response assessment that was stable disease or better. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD and PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions. |
| Phase 2- Disease Control Rate (DCR) | Phase 2: Day 21 of every other cycle (Cycle 2, 4, 6, 8) up to EOT (approximately 1 year) | DCR is defined as Complete Response (CR) rate + Partial Response (PR) rate + stable disease (SD) rate with a minimum of 12 weeks' duration. Duration of SD is defined as the time from the date of first study drug administration to the date of first documentation of disease progression for participants who achieved SD as the best overall response. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions) and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Phase 2- Overall Survival (OS) | Baseline up to EOT thereafter every 12 weeks until death or the start of subsequent antineoplastic therapy, or 6 months after discontinuation from treatment, whichever occurs first (total duration of assessment up to 1.5 years) | OS is defined as the time from the date of first study drug administration to the date of death. Participants without documentation of death at the time of analysis were censored at the date when they were last known to be alive. |
| Phase 2- Plasma Concentration of MLN0264 | Day 1 of every cycle (up to 1 year): predose and at multiple time points(up to 336 hours) post-dose | — |
| Phase 2- Tumor Size Reduction | Baseline up to approximately 1 year | For each participant, the best percentage of tumor reduction from baseline in the sum of the diameter was calculated. |
| Phase 2- Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC) | Baseline up to approximately 1 year | The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors. The score is obtained by the formula: 3 \* percentage of strongly staining nuclei + 2 \* percentage of moderately staining nuclei + percentage of weakly staining nuclei, giving a range of 0 to 300. The 600 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 |
| Phase 2- Number of Participants With ATA in Serum | Baseline up to approximately 1 year | Blood samples were to be collected predose to evaluate ATA. |
| Phase 1- Number of Participants With Antitherapeutic Antibodies (ATAs) | Day 1 of Cycle 1, 2, 3, 4: predose | Blood samples was collected predose to evaluate ATA. Data was collected only for limited period due to early termination of the study. |
Countries
Japan, South Korea, Taiwan
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in Korea, Japan, and Taiwan from 1 December 2014 to 7 October 2015. The study was terminated during the dose-escalation portion of phase 1 and phase 2 was not initiated.
Pre-assignment details
Participants with a historical diagnosis of gastrointestinal carcinoma were enrolled in 1 of 3 treatment groups: MLN0264 1.2 milligram per kilogram (mg/kg), MLN0264 1.5 mg/kg or MLN0264 1.8 mg/kg during Phase 1.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: All Participants Participants who either received MLN0264 1.2 mg/kg as starting dose, or 1.5 mg/kg, or 1.8 mg/kg infusion, intravenously over 30 minutes, on Day 1 of every 3 week cycle of Phase 1, for up to 1 year or until disease progression or unacceptable toxicity. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Progressive disease | 3 | 3 | 6 |
Baseline characteristics
| Characteristic | Phase 1: All Participants |
|---|---|
| Age, Customized Between 45 to 78 years | 12 participants |
| Eastern Cooperative Oncology Group (ECOG) Therapy 0 | 8 participants |
| Eastern Cooperative Oncology Group (ECOG) Therapy 1 | 4 participants |
| Histological classification Adenocarcinoma not otherwise specified | 1 participants |
| Histological classification Colon cancer | 2 participants |
| Histological classification Gastric cancer | 2 participants |
| Histological classification Invasive ductal carcinoma of the pancreas | 1 participants |
| Histological classification Lymphovascular invasion | 1 participants |
| Histological classification Moderately differentiated and descending colon | 1 participants |
| Histological classification Moderately differentiated ductal adenocarcinoma | 1 participants |
| Histological classification Rectal cancer | 2 participants |
| Histological classification Tubular adenocarcinoma | 1 participants |
| Participants With Prior Anticancer Therapy | 12 participants |
| Participants With Prior Medical Condition | 12 participants |
| Participants With Prior Radiation Therapy Without prior radiation therapy | 10 participants |
| Participants With Prior Radiation Therapy With prior radiation therapy | 2 participants |
| Participants With Surgical History Without Surgical History | 4 participants |
| Participants With Surgical History With Surgical History | 8 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 4 participants |
| Region of Enrollment Korea, Republic of | 7 participants |
| Region of Enrollment Taiwan | 1 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 4 / 12 |
Outcome results
Primary
Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | 42.97 day*mcg/mL | Standard Deviation 4.667 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | 63.58 day*mcg/mL | Standard Deviation 6.444 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | 60.09 day*mcg/mL | Standard Deviation 7.33 |
Primary
Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE | 8.510 day*ng/mL | Standard Deviation 0.0424 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE | 17.170 day*ng/mL | Standard Deviation 5.0302 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE | 53.172 day*ng/mL | Standard Deviation 53.8275 |
Primary
Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb | 68.82 day*mcg/mL | Standard Deviation 22.91 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb | 154.95 day*mcg/mL | Standard Deviation 5.657 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb | 149.65 day*mcg/mL | Standard Deviation 31.321 |
Primary
Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264 | 41.37 day*mcg/mL | Standard Deviation 4.667 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264 | 59.63 day*mcg/mL | Standard Deviation 6.902 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264 | 57.88 day*mcg/mL | Standard Deviation 7.032 |
Primary
Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE | 15.846 day*ng/mL | Standard Deviation 27.9611 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE | 16.840 day*ng/mL | Standard Deviation 4.7596 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE | 52.327 day*ng/mL | Standard Deviation 51.8349 |
Primary
Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb | 69.82 day*mcg/mL | Standard Deviation 20.647 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb | 116.59 day*mcg/mL | Standard Deviation 20.775 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb | 112.46 day*mcg/mL | Standard Deviation 30.653 |
Primary
Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The Pharmacokinetic (PK) evaluable population included all participants who received greater than or equal to (\>=1) dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264 | 25.62 microgram per milliliter (mcg/mL) | Standard Deviation 0.907 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264 | 33.84 microgram per milliliter (mcg/mL) | Standard Deviation 6.275 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for MLN0264 | 35.77 microgram per milliliter (mcg/mL) | Standard Deviation 7.342 |
Primary
Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | 2.002 nanogram per milliliter (ng/mL) | Standard Deviation 2.9479 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | 2.335 nanogram per milliliter (ng/mL) | Standard Deviation 0.3889 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE) | 6.614 nanogram per milliliter (ng/mL) | Standard Deviation 4.6853 |
Primary
Phase 1: Cycle 1- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb)
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) | 24.53 mcg/mL | Standard Deviation 2.179 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) | 32.12 mcg/mL | Standard Deviation 9.18 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb) | 36.31 mcg/mL | Standard Deviation 7.709 |
Primary
Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264 | 0.201 mcg/mL | Standard Deviation 0.0113 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264 | 0.309 mcg/mL | Standard Deviation 0.049 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264 | 0.261 mcg/mL | Standard Deviation 0.0831 |
Primary
Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE | 0.049 ng/mL | Standard Deviation 0.0665 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE | 0.037 ng/mL | Standard Deviation 0.0025 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE | 0.157 ng/mL | Standard Deviation 0.3717 |
Primary
Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 1 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb | 0.835 mcg/mL | Standard Deviation 0.4912 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb | 1.479 mcg/mL | Standard Deviation 0.0794 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb | 1.140 mcg/mL | Standard Deviation 0.9592 |
Primary
Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | 0.03 day |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | 0.03 day |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | 0.03 day |
Primary
Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | 2.04 day |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | 2.88 day |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | 2.45 day |
Primary
Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb
Time frame: Day 1 of Cycle 1: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | 0.03 day |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | 0.03 day |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 1- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | 0.03 day |
Primary
Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | 31.81 day*mcg/mL | Standard Deviation 11.314 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | 74.40 day*mcg/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MLN0264 | 61.52 day*mcg/mL | Standard Deviation 18.88 |
Primary
Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE | 16.600 day*ng/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for MMAE | 37.212 day*ng/mL | Standard Deviation 12.5158 |
Primary
Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb | 192.00 day*mcg/mL |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- AUCinf: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for TAb | 204.00 day*mcg/mL |
Primary
Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm as none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264 | 71.60 day*mcg/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MLN0264 | 58.03 day*mcg/mL | Standard Deviation 19.233 |
Primary
Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE | 16.400 day*ng/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for MMAE | 36.603 day*ng/mL | Standard Deviation 12.1622 |
Primary
Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb | 164.00 day*mcg/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- AUCint: Area Under the Serum/Plasma Concentration-time Curve From Time 0 to End of the 21-day Dosing Interval (AUCint) for TAb | 147.21 day*mcg/mL | Standard Deviation 32.527 |
Primary
Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264 | 20.99 mcg/mL | Standard Deviation 0.755 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264 | 29.46 mcg/mL | Standard Deviation 9.18 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MLN0264 | 31.11 mcg/mL | Standard Deviation 6.874 |
Primary
Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MMAE
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MMAE | 2.777 ng/mL | Standard Deviation 5.0507 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MMAE | 2.611 ng/mL | Standard Deviation 1.1907 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Cmax: Maximum Observed Plasma Concentration for MMAE | 6.976 ng/mL | Standard Deviation 5.6196 |
Primary
Phase 1: Cycle 2- Cmax: Maximum Observed Serum Concentration for TAb
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 2- Cmax: Maximum Observed Serum Concentration for TAb | 24.28 mcg/mL | Standard Deviation 3.592 |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Cmax: Maximum Observed Serum Concentration for TAb | 33.33 mcg/mL | Standard Deviation 9.454 |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Cmax: Maximum Observed Serum Concentration for TAb | 36.54 mcg/mL | Standard Deviation 6.471 |
Primary
Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm as none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264 | 0.365 mcg/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MLN0264 | 0.369 mcg/mL | Standard Deviation 0.0283 |
Primary
Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE | 0.057 ng/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for MMAE | 0.117 ng/mL | Standard Deviation 0.0824 |
Primary
Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day1 PK assessment were available. Data is not reported for MLN0264 1.2 mg/kg arm because none of the participants had data evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb | 2.300 mcg/mL | — |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Ctrough: Observed Concentration Measured at the End of a Dosing Interval for TAb | 2.560 mcg/mL | Standard Deviation 0.0424 |
Primary
Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MLN0264 concentration time data to permit reliable estimation of MLN0264 exposure where Cycle 2 Day 1 PK assessment were available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | 0.03 day |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | 0.03 day |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN0264 | 0.03 day |
Primary
Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient MMAE concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | 2.03 day |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | 2.00 day |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE | 2.89 day |
Primary
Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb
Time frame: Day 1 of Cycle 2: predose and at multiple time points (up to 336 hours) post-dose
Population: The PK evaluable population included all participants who received \>=1 dose of MLN0264 and had sufficient TAb concentration time data to permit reliable estimation of the PK parameters where Cycle 2 Day 1 PK assessment were available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: All Participants | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | 0.03 day |
| Phase 1: MLN0264 1.5 mg/kg | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | 0.03 day |
| Phase 1: MLN0264 1.8 mg/kg | Phase 1: Cycle 2- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb | 0.03 day |
Primary
Phase 1- Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Toxicity evaluated as per NationalCancerInstituteCommonTerminologyCriteria for AEs (NCI CTCAE),version 4.03.DLT=any event related to MLN0264:Grade 4 neutropenia(absolute neutrophil count\[ANC\]less than\[\<\]500 cells/millimeter\[mm\]\^3); \>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle greater than (\>)2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.
Time frame: Phase 1: Up to Cycle 1 (3 weeks)
Population: The DLT-Evaluable population included all participants who either experienced DLT during Cycle 1 or received their scheduled Cycle 1 dose and completed all study procedures in Cycle 1 without DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Phase 1- Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | 0 participants |
Primary
Phase 1- Number of Participants Reporting One or More Serious Adverse Events (SAE)
Time frame: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)
Population: Safety population included all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Phase 1- Number of Participants Reporting One or More Serious Adverse Events (SAE) | 4 participants |
Primary
Phase 1- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)
Time frame: Phase 1: Baseline through 30 days after the last dose of study drug (approximately up to 35 weeks)
Population: Safety population includes all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Phase 1- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 10 participants |
Primary
Phase 1- Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (beats per minute \[bpm\]).
Time frame: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)
Population: Safety population included all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Phase 1- Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 participants |
Primary
Phase 1- Number of Participants With Markedly Abnormal Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Laboratory assessment includes serum chemistry, hematology, urine analysis and coagulation.
Time frame: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)
Population: Safety population included all participants who received any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: All Participants | Phase 1- Number of Participants With Markedly Abnormal Laboratory Values | Serum Chemistry | 10 participants |
| Phase 1: All Participants | Phase 1- Number of Participants With Markedly Abnormal Laboratory Values | Hematology | 12 participants |
| Phase 1: All Participants | Phase 1- Number of Participants With Markedly Abnormal Laboratory Values | Urinalysis | 1 participants |
| Phase 1: All Participants | Phase 1- Number of Participants With Markedly Abnormal Laboratory Values | Coagulation | 5 participants |
Primary
Phase 1- Recommended Phase 2 Dose (RP2D)
RP2D is maximum tolerated dose(MTD) in study Phase1.MTD was highest dose of MLN0264 given at which \<=1 of 6 participants experienced DLTduring Cycle1 of Phase1.DLT=any event related to MLN0264:Grade 4 neutropenia ANC less than\<500 cells mm\^3;\>=Grade 3 neutropenia with fever/infection;Grade 4 thrombocytopenia(platelets \<25,000/mm\^3)/requires platelet transfusion(with/without hemorrhage);Grade 3/greater thrombocytopenia with clinically meaningful bleeding;Anemia requiring blood transfusion;\>=Grade 3 nausea/emesis occurring despite using optimal anti-emetic prophylaxis;\>=Grade 3 diarrhea despite optimal supportive care measures;any other \>=Grade 3 nonhematologic toxicity except brief(\<1 week)Grade 3 fatigue;Inability to start next therapy cycle\>2 weeks due to delayed treatment and adequate recovery of MLN0264-related hematologic or nonhematologic toxicity;other\>= Grade 2 MLN0264-related nonhematologic toxicity which requires dose reduction or discontinuation of therapy.
Time frame: Phase 1: Baseline through 30 days after the last dose of study drug (Approximately up to 35 weeks)
Population: The DLT-Evaluable population included all participants who either experienced DLT during Cycle 1 or received their scheduled Cycle 1 dose and completed all study procedures in Cycle 1 without DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Phase 1- Recommended Phase 2 Dose (RP2D) | NA mg/kg |
Primary
Phase 2- Overall Response Rate
ORR is the percentage of participants with complete response \[CR\] + partial response \[PR\]) based on modified Response Evaluation Criteria in Solid Tumors (RECIST). Overall response rate (CR + PR) based on modified RECIST version 1.1 guidelines. CR: Disappearance of all target lesions and PR: at least a 30 percentage (%) decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total representative of all involved organs were identified as target lesions at baseline. Target lesions were selected on the basis of size (longest lesions) and suitability for reproducible repeated measurements.
Time frame: Baseline until end of study treatment (approximately 1 year)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 1- Disease Response Based on the Investigator's Assessment
Disease response was based on the investigator's assessment using the modified RECIST version 1.1 guidelines. Evaluation of target lesions included CR (Disappearance of all target lesions),PR(at least a 30% decrease in the sum of the LD of target lesions),Progressive disease (PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions) and Stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD).Evaluation of Non target Lesions included CR (disappearance of all non target lesions and normalization of tumor marker level), Incomplete response/SD (Persistence of 1 or more non target lesions and/or maintenance of tumor marker level above the normal limits) and PD(Appearance of 1 or more new lesions and/or unequivocal progression of existing non target lesions).
Time frame: Phase 1: Day 21 of every other cycle (Cycle 2, 4, 6, 8) up to End of treatment (EOT) (Cycle10 or week 30)
Population: The Response-Evaluable population is 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 | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: All Participants | Phase 1- Disease Response Based on the Investigator's Assessment | CR | 0 participants |
| Phase 1: All Participants | Phase 1- Disease Response Based on the Investigator's Assessment | PR | 0 participants |
| Phase 1: All Participants | Phase 1- Disease Response Based on the Investigator's Assessment | SD | 0 participants |
| Phase 1: All Participants | Phase 1- Disease Response Based on the Investigator's Assessment | PD | 12 participants |
Secondary
Phase 1- Number of Participants With Antitherapeutic Antibodies (ATAs)
Blood samples was collected predose to evaluate ATA. Data was collected only for limited period due to early termination of the study.
Time frame: Day 1 of Cycle 1, 2, 3, 4: predose
Population: Safety population included all participants who received any amount of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Phase 1- Number of Participants With Antitherapeutic Antibodies (ATAs) | 0 participants |
Secondary
Phase 2- Disease Control Rate (DCR)
DCR is defined as Complete Response (CR) rate + Partial Response (PR) rate + stable disease (SD) rate with a minimum of 12 weeks' duration. Duration of SD is defined as the time from the date of first study drug administration to the date of first documentation of disease progression for participants who achieved SD as the best overall response. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions) and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Phase 2: Day 21 of every other cycle (Cycle 2, 4, 6, 8) up to EOT (approximately 1 year)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documentation of Progressive Disease (PD). Responders without documentation of PD were censored at the last response assessment that was stable disease or better. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD and PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions.
Time frame: Day 21 of every other cycle (Cycle 2, 4, 6, 8) up to EOT (approximately 1 year)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC)
The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors. The score is obtained by the formula: 3 \* percentage of strongly staining nuclei + 2 \* percentage of moderately staining nuclei + percentage of weakly staining nuclei, giving a range of 0 to 300. The 600 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
Time frame: Baseline up to approximately 1 year
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Number of Participants With ATA in Serum
Blood samples were to be collected predose to evaluate ATA.
Time frame: Baseline up to approximately 1 year
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs include body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (beats per minute \[bpm\]).
Time frame: Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Number of Participants With Markedly Abnormal Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Laboratory assessment includes serum chemistry, hematology, urine analysis and coagulation.
Time frame: Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Overall Survival (OS)
OS is defined as the time from the date of first study drug administration to the date of death. Participants without documentation of death at the time of analysis were censored at the date when they were last known to be alive.
Time frame: Baseline up to EOT thereafter every 12 weeks until death or the start of subsequent antineoplastic therapy, or 6 months after discontinuation from treatment, whichever occurs first (total duration of assessment up to 1.5 years)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Percentage of Participants Who Experience at Least One SAE
Time frame: Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Percentage of Participants Who Experience at Least One TEAE
Time frame: Phase 2: Baseline up to 30 days after last dose of study drug (approximately 1 year)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Plasma Concentration of MLN0264
Time frame: Day 1 of every cycle (up to 1 year): predose and at multiple time points(up to 336 hours) post-dose
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Progression-free Survival (PFS)
PFS is defined as the time from the date of first study drug administration to the date of first documentation of progressive disease or death. For a participant who has not progressed and is last known to be alive, PFS was censored at the last response assessment that was stable disease or better. PD:at least a 20% increase in the sum of the LD of target lesions, taking the smallest sum LD recorded as reference since the treatment started or the appearance of one or more new lesions.
Time frame: Baseline up to EOT, thereafter every 12 weeks until the occurrence of PD, the start of subsequent antineoplastic therapy, or 6 months after discontinuation from treatment, whichever occurs first (total duration of assessment up to 1.5 years)
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.
Secondary
Phase 2- Tumor Size Reduction
For each participant, the best percentage of tumor reduction from baseline in the sum of the diameter was calculated.
Time frame: Baseline up to approximately 1 year
Population: Data was not reported for this measure as Phase 2 was not initiated, due to study termination during the dose-escalation portion of phase 1 consistent with the findings that preliminary PK and overall clinical data demonstrated compelling similarity between Western and Asian participant populations.