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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01943864 | A Phase IIa Study of the MEK Inhibitor Trametinib Monotherapy in the Treatment of Biliary Tract Cancers | PHASE2 | COMPLETED | 20 | — | — | Sep 19, 2013 | Feb 1, 2016 | May 31, 2017 | 5 | Japan |
| NCT02065063 | A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Anti-Cancer Activity of Trametinib in Combination With Palbociclib in Subjects With Solid Tumors | PHASE1 | COMPLETED | 28 | — | — | Apr 22, 2014 | Jun 23, 2016 | Jun 1, 2018 | 3 | United States |
| NCT01647659 | Relative Bioavailibilty for Pediatric Powder for Suspension (PfOS) Formulation | PHASE1 | COMPLETED | 18 | — | — | Jul 30, 2012 | Nov 12, 2012 | Nov 13, 2017 | 2 | United States |
| NCT01192165 | Safety and Tolerability Study of GSK1120212, a MEK Inhibitor, in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel | PHASE1 | COMPLETED | 169 | — | — | Sep 14, 2010 | Oct 7, 2013 | Nov 13, 2017 | 20 | United States, Canada +2 |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the diameters of target lesions; Stable Disease(SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease(PD), At least a 20% increase in the sum of the diameters of target lesions. Non-PD = CR + PR + SD.
Twelve week non-progressive disease (PD) at Week 12 was evaluated by computed tomography. Non- PD was calculated as the sum of complete response (CR), partial response (PR), and stable disease (SD).
Vital sign measurements will include systolic and diastolic blood pressure, temperature, respiration rate and pulse rate
A complete physical examination will include assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities
An ECHO (preferred) or a MUGA scan will be performed at baseline to assess cardiac ejection fraction and cardiac valve morphology for the purpose of study eligibility
All subjects (approximately 50)
PK parameters will include: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve (AUC\[0-t\]), oral clearance (CL/F), minimum observed concentration (Cmin). Blood samples of approximately 2 mL for trametinib and 2 mL for palbociclib (4 mL total) will be collected for PK analysis at each timepoint shown for all subjects (approximately 50)
Disease progression and response evaluations will be determined according to the definitions established in the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) for all subjects (approximately 50 in Part 1)
Change from baseline in biomarkers like pERK, total Rb, Ki67, FoxM1, p16, and CCDN1 will be calculated. These markers will be evaluated in formalin-fixed, paraffin-embedded tissue via immunohistochemistry (IHC)
| Arm | Type | Description |
|---|---|---|
| Trametinib (single tablet) | EXPERIMENTAL | Subjects will receive, trametinib once daily as a single tablet of 2 mg administered orally with eight ounces of water under fasting conditions either one hour before or 2 hours after a meal. |
| Trametinib PK study (multiple tablet) | EXPERIMENTAL | Subjects will receive on Day 1, trametinib as four tablets of 0.5 mg administered orally with eight ounces of water under fasting conditions either one hour before or 2 hours after a meal. |
| Trametinib PK study (single tablet) | EXPERIMENTAL | Subjects will receive Day 2 onwards, trametinib once daily as a single tablet of 2 mg administered orally with eight ounces of water under fasting conditions either one hour before or 2 hours after a meal. |
| Part 1 | EXPERIMENTAL | Part 1 is a dose finding phase in which subjects will be initially administered 75 milligram (mg) of palbociclib (21 days on/7 days off) and 1.5 mg of trametinib (once daily continuous dosing) in each 28-day cycle. Dose escalations will continue based on predefined parameters until the RCR is identified. The RCR will not exceed the maximum tolerated dose (MTD). |
| Part 2 | EXPERIMENTAL | Once the MTD and schedule have been determined, two expansion cohorts of up to 20 subjects each will be enrolled. The cohorts will enroll subjects with BRAF-WT (wild type) cutaneous melanoma that are either NRAS-WT or NRAS-MUT (mutated). Subjects will be dosed at or below the RCR to determine the inhibition of selected tumor biomarkers at each dose level. |
| Part 3 | EXPERIMENTAL | Part 3 will be a randomized Phase II study in which subjects will be administered the RCR as previously identified. Part 3 will be initiated only if an RCR is identified, and sufficient anticancer activity is observed in Parts 1 and 2. |
| GSK1120212 tablet | EXPERIMENTAL | GSK1120212 tablet |
| GSK1120212 powder for oral solution | EXPERIMENTAL | GSK1120212 powder for oral solution |
| Treatment Group 1 | EXPERIMENTAL | Trametinib plus Docetaxel |
| Treatment Group 2 | EXPERIMENTAL | Trametinib plus Erlotinib |
| Treatment Group 3 | EXPERIMENTAL | Trametinib plus Pemetrexed |
| Treatment Group 4 | EXPERIMENTAL | Trametinib plus Pemetrexed and Carboplatin |
| Treatment Group 5 | EXPERIMENTAL | Trametinib plus nab-Paclitaxel |
| Treatment Group 6 | EXPERIMENTAL | Trametinib plus Pemetrexed and Cisplatin |
| Name | Type | Description |
|---|---|---|
| Trametinib (single tablet) | DRUG | The drug substance is blended with inert |
| Trametinib (Multiple tablet) | DRUG | The drug substance is blended with inert |
| Trametinib | DRUG | Trametinib is available as a 0.5 mg yellow oval tablet or as a 2.0 mg pink round tablet. |
| Palbociclib | DRUG | Palbociclib is available as a 75 mg (size 2 sunset yellow) or 100 mg (size 1 sunset yellow/caramel) or 125 mg (size 0 caramel) capsule. |
| Trametinib tablet | DRUG | 2 mg, orally, on Day 1 of the dosing period |
| Trametinib pediatric formulation | DRUG | 2 mg, orally, on Day 1 of the dosing period |
| Trametinib (GSK1120212) | DRUG | Investigational small molecule targeted therapy (MEK1/2 inhibitor) |
| Docetaxel | DRUG | Chemotherapy |
| Erlotinib | DRUG | Small molecule targeted therapy (EGFR inhibitor) |
| Pemetrexed | DRUG | Chemotherapy |
| Carboplatin | DRUG | Chemotherapy |
| nab-Paclitaxel | DRUG | Chemotherapy |
| Cisplatin | DRUG | Chemotherapy |
Inclusion Criteria: * Male or female of age 20 years or older inclusive, at the time of signing the informed consent. * Japanese patients with histologically or cytologically confirmed cholangiocarcinoma (intra- or extrahepatic) or gallbladder cancer or ampulla of Vater cancer are eligible for whic...
| 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 |