Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication MEKINIST is a kinase inhibitor indicated as a single agent for the treatment of BRAF-inhibitor treatment-naïve patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. FDA label
Also known as Mekinist, TMT212
trametinib · 3 trials · 3 indications
The primary outcome of N-cadherin and vimentin expression will be measured in post-treatment RP specimens. Comparisons amongst the various treatment groups (post-treatment inter-group) will be performed after all data have been collected.
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 |
|---|---|---|
| AR inhibition only | ACTIVE_COMPARATOR | AR inhibition only Group 1: degarelix + enzalutamide Endocrine therapy with degarelix and enzalutamide will continue for a minimum of 6 weeks and a maximum of 8 weeks in all groups prior to the planned prostatectomy. |
| AR inhibition plus MEK inhibition | ACTIVE_COMPARATOR | AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks. |
| AR inhibition plus SRC inhibition | ACTIVE_COMPARATOR | AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks. |
| 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 |
|---|---|---|
| degarelix | DRUG | Every 4-week Treatment: A starting dose of 240 mg of Degarelix is taken subcutaneously (SQ) -placed under the skin by injection- the first month. Doses continue every 4 weeks at 80 mg SQ. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician. |
| enzalutamide | DRUG | Once Daily Treatment: A starting dose of 160 mg of Enzalutamide is taken by mouth once daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician. |
| trametinib | DRUG | Once Daily Treatment: If randomized into Group 2, then 2mg of Trametinib is taken by mouth daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician |
| dasatinib | DRUG | Once Daily Treatment: If randomized into Group 3, then 100mg of Dasatinib is taken by mouth daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician |
| 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 (patients must meet all of the following inclusion criteria to participate in this study) 1. Willing and able to give informed consent. 2. Adenocarcinoma of the prostate with planned RP with curative intent as part of standard of care management plan. 3. Patient is a candidate fo...
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Trametinib is a small molecule drug being developed by Novartis AG for oncology indications, including cancer, prostate cancer, and solid tumors. It is an inhibitor of the MAP2K1 and MAP2K2 targets and is currently in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA.
Trametinib is being studied for the treatment of cancer, prostate cancer, and solid tumors. Clinical trials have evaluated it in patients with solid tumors, cancers harboring V600 mutations, plexiform neurofibromas, and prostate cancer. It remains investigational and is not approved for any indication.
Trametinib targets MAP2K1 and MAP2K2, also known as MEK1 and MEK2. It is classified as an inhibitor of these kinases. By inhibiting MAP2K1 and MAP2K2, trametinib acts on the MAPK signaling pathway, which is relevant in cancers driven by mutations such as V600.
Trametinib is developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor of the clinical trials evaluating trametinib in cancer, prostate cancer, and solid tumors.
Trametinib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. The Phase 1 program includes studies in solid tumors and in cancers or plexiform neurofibromas, including combination treatment with dabrafenib in cancers harboring V600 mutations.
Trametinib has been evaluated in trials including NCT02705963, a Phase 1 drug-drug interaction study in female patients with solid tumors, and NCT02124772, a Phase 1 study in cancer and plexiform neurofibromas. A Phase 2 study, NCT01990196, evaluated MEK inhibition in prostate cancer and is active but not recruiting.