Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02124772 | Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations | PHASE1 | COMPLETED | 139 | — | — | Jan 15, 2015 | Dec 29, 2020 | Jul 14, 2021 | 16 | United States, Australia +3 |
Incidence of treatment emergent adverse events is defined as number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes from baseline in vital signs and laboratory results qualifying and reported as AEs. The number of participants in each category is reported in the table.
Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. The average steady state plasma concentration (Cavg) of trametinib was calculated as the ratio of area under the curve (AUC)/tau, where tau = 24 h for trametinib.
| Arm | Type | Description |
|---|---|---|
| Part A - TMT 0.0125 mg/kg/day | EXPERIMENTAL | Participants treated with trametinib 0.0125 mg/kg/day |
| Part A - TMT 0.025 mg/kg/day | EXPERIMENTAL | Participants treated with trametinib 0.025 mg/kg/day |
| Part A - TMT 0.032 mg/kg/day | EXPERIMENTAL | Participants under 6 years of age treated with trametinib 0.032 mg/kg/day |
| Part A - TMT 0.04 mg/kg/day | EXPERIMENTAL | Participants treated with trametinib 0.04 mg/kg/day |
| Part B - Neuroblastoma | EXPERIMENTAL | Participants with refractory or relapsed neuroblastoma treated with trametinib 0.025 mg/kg/day |
| Part B - LGG fusion | EXPERIMENTAL | Participants with refractory or relapsed neuroblastoma treated with trametinib 0.025 mg/kg/day |
| Part B - NF-1 with PN | EXPERIMENTAL | Participants with neurofibromatosis Type -1 associated plexiform neurofibromas (NF-1 with PN) treated with trametinib 0.025 mg/kg/day |
| Part B - BRAF V600 mutant solid tumor | EXPERIMENTAL | Participants with BRAF V600 mutant solid tumors treated with trametinib 0.025 mg/kg/day |
| Part C - TMT 0.025 mg/kg/day + 50% DRB RP2D | EXPERIMENTAL | Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 50% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (2.63 mg/kg/day for \<12 years old subjects and 2.25 mg/kg/day for ≥12 years old subjects) |
| Part C - TMT 0.025 mg/kg/day + 100% DRB RP2D | EXPERIMENTAL | Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects) |
| Part C - TMT 0.032 mg/kg/day + 100% DRB RP2D | EXPERIMENTAL | Participants under 6 years of age treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day) |
| Part D - LGG | EXPERIMENTAL | Participants with low grade glioma (LGG) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects) |
| Part D - LCH | EXPERIMENTAL | Participants with Langerhans cell histiocytosis (LCH) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects) |
| Name | Type | Description |
|---|---|---|
| Trametinib | DRUG | Trametinib was administered orally, once daily. It was available in tablets (0.125 mg, 0.5 mg, 2 mg dose) as well as in powder form for oral solution (0.05 mg/mL dose). |
| Dabrafenib | DRUG | Dabrafenib was administered orally, twice daily. The daily dose was divided into two equal doses. It was available in capsules (50 mg and 75 mg), dispersible tablets (10 mg) and powder for oral suspension (10 mg/mL dose). |
Inclusion Criteria: * General Eligibility Criteria (All Parts) * Written informed consent - a signed informed consent and/or assent (as age appropriate) for study participation including PK sampling will be obtained according to institutional guidelines. * Male or female between one month and \<18 ...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GE Healthcare Technologies Inc. | GEHC | 1 | PHASE1 | GEH200520 / GEH200521 - Part A |
| Zimmer Biomet Holdings, Inc. | ZBH | 1 | — | Undisclosed |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | Olverembatinib |