Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Trametinib · 2 trials · 2 indications
To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.
To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.
To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.
To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.
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 |
|---|---|---|
| Oral Contraceptive / Trametinib | EXPERIMENTAL | In treatment period 1 of the PK Phase patients will take the Oral Contraceptive once daily from Days 1-5. Period 2 of the PK Phase starts on Day 6 when patients take both the Oral Contraceptive and trametinib once daily from Days 6 to 21. Patients may continue dosing with trametinib only once daily from Day 22 onwards (post PK Phase). |
| 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 | Each tablet is 2mg trametinib to be taken orally once daily. |
| Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol) | DRUG | Combined oral contraceptive to be taken orally once daily. |
| 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: * Has a histologically or cytologically confirmed diagnosis of a solid tumor malignancy (except for any excluded malignancies listed in the Exclusion Criteria) that is not responsive to standard therapy(ies) or for which there is no approved therapy. * Meets one of the following...
| 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 |
Trametinib is an investigational small molecule being studied for the treatment of cancer and solid tumors. It is being developed by Novartis AG (NVS). Clinical trials have investigated its safety, pharmacokinetics, pharmacodynamics, and clinical activity in subjects with cancer or plexiform neurofibromas, as well as in combination with dabrafenib in cancers harboring V600 mutations.
Trametinib targets MAP2K1 and MAP2K2, which are also known as MEK1 and MEK2. It is a small molecule inhibitor of these kinases, which are part of the RAS/RAF/MEK/ERK signaling pathway involved in cell proliferation. By inhibiting MAP2K1 and MAP2K2, Trametinib is designed to block signaling that can drive tumor growth.
Trametinib is being developed by Novartis AG, which is publicly traded under the ticker NVS. The company is conducting clinical research on this drug candidate for oncology indications, including cancer and solid tumors.
Trametinib is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Clinical trials have been completed, and the drug is still being studied for its safety and activity in patients with cancer and solid tumors.
Trametinib has been studied in two Phase 1 clinical trials. NCT02124772 investigated its safety, pharmacokinetics, pharmacodynamics, and clinical activity in subjects with cancer or plexiform neurofibromas, including combination with dabrafenib in V600 mutation cancers. NCT02705963 assessed its effect on oral contraceptive pharmacokinetics in female patients with solid tumors.
Trametinib is the generic name for the drug also known as Mekinist. In clinical trials, it has been studied alone and in combination with dabrafenib for cancers with V600 mutations. The drug is being developed by Novartis AG for oncology indications.