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 a kinase inhibitor, belonging to the -tinib class of drugs. Clinical trials have investigated its use in patients with cancer, including those with plexiform neurofibromas, and in combination with dabrafenib for cancers harboring V600 mutations.
Trametinib targets kinases, as it belongs to the -tinib class of kinase inhibitors. It is being studied for its effects on cancer and solid tumors, with clinical trials exploring its activity in patients with V600 mutations when used in combination with dabrafenib.
Trametinib is being developed by Novartis AG, a company traded on the stock exchange under the ticker symbol NVS. The drug is currently in clinical development for oncology indications, including cancer and solid tumors.
Trametinib is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. Clinical trials are ongoing to evaluate its safety, pharmacokinetics, pharmacodynamics, and clinical activity in patients with cancer and solid tumors.
Trametinib has been studied in clinical trials registered under NCT02124772 and NCT02705963. NCT02124772 investigated its safety and activity in cancer or plexiform neurofibromas, and in combination with dabrafenib for V600 mutations. NCT02705963 assessed its effect on oral contraceptive pharmacokinetics in female patients with solid tumors.
Trametinib is the active ingredient in the drug product Mekinist, which is approved for certain cancers. However, the clinical trials described here are investigating trametinib as an investigational agent, and the information provided does not specify whether these trials are for the approved product or for new indications.