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MLN0264

Phase 1

Advanced Gastrointestinal Malignancies | Small molecule | Gastrointestinal |Takeda Pharmaceutical Company Limited|Last Updated: Sep 7, 2016

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
UNCONTROLLEDBiomarker
Total Trials1
Total Enrollment41
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01577758Phase 1 Study of MLN0264 in Adult Patients With Advanced Gastrointestinal Malignancies Expressing Guanylyl Cyclase CPHASE1 COMPLETED 41Jun 1, 2012Feb 1, 2014Sep 7, 20161 United States
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Study Endpoints
Primary Endpoints
Number of Participants With Dose-Limiting Toxicities (DLTs)
From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months

DLT was defined as any of the following Adverse Events (AEs) that occur and are considered by the investigator to be related to therapy. 1. Grade 4 neutropenia (Absolute Neutrophil Count \< 500 cells/mm\^3). 2. Grade 3 or greater neutropenia with fever and/or infection. 3. Grade 4 thrombocytopenia (platelets \< 25,000/mm\^3). 4. Grade 3 or greater thrombocytopenia with clinically meaningful bleeding at any time. 5. Grade 3 or greater nausea and/or emesis that occurs despite of prophylaxis. 6. Grade 3 or greater diarrhea that occurs despite supportive care. 7. Any other Grade 3 or greater non-hematological toxicity other than Grade 3 fatigue or Grade 3 Alopecia. 8. Inability to start the next cycle of therapy due to treatment delay of more than 2 weeks because of lack of recovery. 9. Other MLN0264-related non-hematologic toxicities Grade 2 or greater requiring discontinuation of therapy.

Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
From the time informed consent is signed through 30 days after the last dose of study drug, approximately 9 months

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Maximum Tolerated Dose (MTD) of MLN0264
Every 3 weeks until MTD is established, approximately 9 months

MTD of MLN0264 was determined. Decisions regarding dose escalation were made based on any DLT that occurred during the first cycle of treatment.

Cmax: Maximum Observed Serum Concentration for MLN0264
Cycle 1: Day 1 pre-dose to Day 21 post-dose

Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably.

Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)
Cycle 1: Day 1 pre-dose to Day 21 post-dose

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. Cmax is reported for the 1.8 mg/kg dose, which is the MTD, where there is adequate data to provide robust parameter information reliably.

AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MLN0246
Cycle 1: Day 1 pre-dose to 21 Days post-dose

Area under the drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably.

AUC0-21 Days: Area Under the Curve Day 0 to Day 21 for MMAE
Cycle 1: Day 1 pre-dose to 21 Days post-dose

Area under the plasma drug concentration versus time curve from time 0 to Day 21. AUC0-21 is reported for the 1.8 mg/kg dose (the MTD), where there is adequate data to provide robust parameter information reliably.

Secondary Endpoints
Best Overall Response
At the completion of every second cycle up to 12 cycles (approximately 9 months). Each cycle is a 21 days cycle
Number of Participants With Antitherapeutic Antibodies (ATA)
Day 1 of every 21 days cycle and at End of study (EOS) approximately 9 months
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
MLN0264EXPERIMENTALMLN0264 starting dose 0.3 mg/kg escalated until Maximum Tolerated Dose (MTD) was determined, 30-minute infusion, on Day 1 of each 21-Day treatment cycle.
Interventions
NameTypeDescription
MLN0264DRUGMLN0264 30-minute infusion on Day 1 of each treatment cycle
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Voluntary consent form * Diagnosis of GI malignancy with a GCC protein expressing tumor * Male or female patients 18 years or older with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) * Female patients who are post menopausal, surgically...

Countries:United States
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