Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as TAK-228, INK0128, INK128, TAK-128
MLN0128 · 4 trials · 4 indications
PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
MTD is the highest dose level at which the participants tolerate treatment without dose-limiting toxicities during the first cycle (28 days) of therapy.
DLT was defined as any of the following occurring during Cycle 1 (Days 1-28) and attributable to MLN0128P: Grade ≥ 3 nonhematologic toxicity; Grade 3 thrombocytopenia with hemorrhage; Grade 4 neutropenia lasting \> 7 days in the absence of growth factor support; Grade 4 neutropenia of any duration associated with fever 38.5 degrees C and/or infection; Any other Grade 4 hematologic toxicity; Inability to administer at least 75 % of doses of MLN0128 within Cycle 1 due to drug-related toxicity; Any clinically significant occurrence which the investigators and sponsor agree would place participants at undue safety risk; Participants who experienced an adverse event (AE) that met the definition for a DLT.
ORR was defined as the percentage of participants with Complete Response (CR) and Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Each cycle was a 28 day cycle. CR was defined as the disappearance of all target lesions and for non-target lesions, the disappearance of all non-target lesions and normalization of tumor marker level. PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions.
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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event is 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.
DLTs were defined as MLN0128-related treatment-emergent adverse events (TEAEs) that occurred within the Cycle 1 (first 28 days of treatment) as per Common Terminology Criteria for Adverse Events (CTCAE): Any ≥Grade 3 or non-hematologic toxicity except for Grade 3 nausea and/or vomiting and diarrhea, Grade 3 hyperglycemia lasting ≤ 14 days, Grade 3 rash lasting ≤ 3 days; Grade 4 neutropenia lasting \>7 days in the absence of growth factor support; Grade 4 neutropenia of any duration associated with fever ≥38.5 degree celsius and/or systemic infection; Any other Grade 4 hematologic toxicity; Inability to administer at least 75% of planned doses of MLN0128 within Cycle 1 due to drug-related toxicity and any clinically significant occurrence that the investigators and sponsor agreed would place participants at an undue safety risk.
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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event is 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.
ORR is defined as the percentage of participants who achieved complete response (CR) or partial response (PR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR is defined as disappearance of all target lesions and PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions. Data was categorized as per type of cancer.
Duration of objective response is defined as the number of months from the start date of CR or PR (whichever occurred first) based on RECIST Criteria version 1.1 to the first date of objectively documented progressive disease (PD) for participants who achieved CR or PR. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Duration of SD was evaluated for participants with best response of SD and is defined as number of months from date of first dose to date of PD. As per RECIST 1.1, SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR was defined of at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions. PD is defined as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this includes baseline sum if that is smallest on study).
| Arm | Type | Description |
|---|---|---|
| Arm A: Single-agent Everolimus 10 mg QD | ACTIVE_COMPARATOR | Everolimus 10 mg capsules, orally, once daily in a 28-day treatment cycle until disease progression, consent withdrawal, death, or transfer to the Post-trial Access (PTA) program (Median duration of treatment was 15.43 weeks up to end of study). |
| Arm B: Single-agent MLN0128 30 mg QW | EXPERIMENTAL | MLN0128 30 mg capsules, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day treatment cycle until disease progression, unacceptable toxicity, consent withdrawal, death, or transfer to the PTA program (Median duration of treatment was 9.64 weeks up to end of study). |
| Arm C: Combination of MLN0128 4 mg QD + MLN1117 200 mg QD | EXPERIMENTAL | MLN0128 4 mg and MLN1117 200 mg capsules, orally, both once daily for 3 days per week (QD X 3) on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day treatment cycle until disease progression, unacceptable toxicity, consent withdrawal, death, or transfer to the PTA program (Median duration of treatment was 9.43 weeks up to end of study). |
| TAK-128 5 mg QD | EXPERIMENTAL | - |
| TAK-128 50 mg QD | EXPERIMENTAL | - |
| TAK-128 100 mg QD | EXPERIMENTAL | - |
| Placebo QD | PLACEBO_COMPARATOR | - |
| MLN0128P 30 mg QW | EXPERIMENTAL | MLN0128 and paclitaxel (MLN0128P): MLN0128 30 mg, capsule, orally, once weekly (QW) + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 40 mg QW | EXPERIMENTAL | MLN0128 40 mg, capsule, orally, once a week (QW) + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 6 mg QD×3d QW | EXPERIMENTAL | MLN0128 6 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 7 mg QD×3d QW | EXPERIMENTAL | MLN0128 7 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 8 mg QD×3d QW | EXPERIMENTAL | MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 9 mg QD×3d QW | EXPERIMENTAL | MLN0128 9 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 10 mg QD×3d QW | EXPERIMENTAL | MLN0128 10 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 7 mg QD×5d QW | EXPERIMENTAL | MLN0128 7 mg, capsule, orally, once daily 5 days on/2 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in the Dose Escalation Phase. |
| MLN0128P 8 mg QD×3d QW HER2- | EXPERIMENTAL | MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 of a 4-week cycle in human epidermal growth factor receptor 2 negative (HER-) cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase. |
| MLN0128PH 8 mg QD×3d QW HER2+ | EXPERIMENTAL | MLN0128 + paclitaxel + trastuzumab (MLN0128PH): MLN0128 8 mg, capsule, orally, once daily 3 days on/4 days off each week + paclitaxel 80 mg/m\^2, 1 hour infusion, on Days 1, 8 and 15 plus trastuzumab 4 mg/kg loading dose on Day 1 followed by 2 mg/kg, intravenous each week of a 4-week cycle in HER+ cancer participants until disease progression or unacceptable toxicity for up to 1 year in the Expansion Phase. |
| MLN0128 QD | EXPERIMENTAL | MLN0128 2 mg, 4 mg, 6 mg or 7 mg, capsule, orally, once daily (QD) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 52.1 weeks). |
| MLN0128 QW | EXPERIMENTAL | MLN0128 7 mg, 10 mg, 15 mg, 20 mg, 30 mg or 40 mg capsule, orally, once weekly (QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 139.4 weeks). |
| MLN0128 QDx3d QW | EXPERIMENTAL | MLN0128 6 mg, 9 mg, 12 mg, 16 mg or 20 mg capsule, orally, once daily every 3 days a week (QDx3d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 129.4 weeks). |
| MLN0128 QDx5d QW | EXPERIMENTAL | MLN0128 7 mg, 10 mg or 13 mg capsule, orally, once daily every 5 days a week (QDx5d QW) in 28-day cycle in the Dose Escalation Phase until Maximum Tolerated Dose (MTD) was established (Up to 161.9 weeks). |
| MLN0128 5 mg QD | EXPERIMENTAL | MLN0128 5 mg, capsule, orally, QD in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 98.3 weeks). |
| MLN0128 30 mg QW | EXPERIMENTAL | MLN0128 30 mg, capsule, orally QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 240 weeks). |
| MLN0128 40 mg QW | EXPERIMENTAL | MLN0128 40 mg, capsule, orally, QW in 28-day cycle until disease progression or unacceptable toxicity in the Dose Expansion Phase (Up to 100.1 weeks). |
| Name | Type | Description |
|---|---|---|
| Everolimus | DRUG | Everolimus capsules. |
| MLN0128 | DRUG | MLN0128 capsules. |
| MLN1117 | DRUG | MLN1117 capsules. |
| TAK-128 | DRUG | TAK-128 5 mg, tablets, orally, once daily for up to 6 months. |
| Placebo | DRUG | TAK-128 placebo-matching tablets, orally, once daily for up to 6 months. |
| paclitaxel | DRUG | paclitaxel intravenous infusion |
| trastuzumab | DRUG | trastuzumab intravenous infusion |
Inclusion Criteria: 1. Male or female participants aged 18 years or older. 2. Histologically confirmed renal cell carcinoma (RCC) with a clear-cell component. 3. Evidence that the RCC is advanced or metastatic. 4. Radiologic evidence of PD (according to RECIST Version 1.1) either during or within 6...
MLN0128 is an investigational small molecule being studied for the treatment of clear-cell metastatic renal cell carcinoma and advanced solid malignancies. It is being developed by Takeda Pharmaceutical Company Limited (TAK) and is currently in clinical development, with completed Phase 1 and Phase 2 trials.
MLN0128 is a small molecule being studied in oncology. While its specific molecular target is not disclosed in the available information, it is being investigated as a potential treatment for advanced solid tumors and clear-cell renal cell carcinoma. The drug is being evaluated alone and in combination with other agents.
MLN0128 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker symbol TAK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with advanced solid malignancies and clear-cell metastatic renal cell carcinoma.
MLN0128 is in clinical development, with completed Phase 1 and Phase 2 trials. It is not FDA approved and remains investigational. The drug has been studied in dose escalation trials for advanced solid malignancies and in a Phase 2 trial for clear-cell metastatic renal cell carcinoma.
MLN0128 has been studied in three completed trials. NCT01058707 was a Phase 1 dose escalation study in advanced solid malignancies with 198 participants. NCT01351350 was a Phase 1 study combining MLN0128 with paclitaxel and trastuzumab in advanced solid and hematologic malignancies with 68 participants. NCT02724020 was a Phase 2 trial comparing MLN0128 to everolimus in clear-cell renal cell carcinoma with 96 participants.
No, MLN0128 is not the same as MLN1117. In clinical trial NCT02724020, MLN0128 was studied alone and in combination with MLN1117, and both were compared to everolimus in patients with advanced or metastatic clear-cell renal cell carcinoma. They are distinct investigational agents.