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Trametinib · 1 trial · 1 indication
The RP2D of combination therapy of trametinib, ruxolitinib and retifanlimab (TR\^2) therapy will be determined as the maximum tolerated dose of combination treatment (in mg) as assessed by treating physician using the NCI-CTCAE Version 5.0.
| Arm | Type | Description |
|---|---|---|
| Part 1 Schedule A: TR^2 Dose Escalation/De-Escalation | EXPERIMENTAL | Participants in this group will receive Trametinib, Ruxolitinib and Retifanlimab in a dose escalation/de-escalation design to determine the maximum tolerated dose (MTD). Participants will receive Trametinib and Ruxolitinib for two weeks on (Days 1-14) and two weeks off (Days 15-28) and Retifanlimab on Day 8 of a 28-day cycle. Doses will be administered as follows: * Dose Level -1A: Trametinib 1 mg orally (PO), Ruxolitinib 5 mg PO, Retifanlimab 500 mg intravenously (IV); * Starting Dose Level 1A: Trametinib 1.5 mg PO, Ruxolitinib 10 mg PO, Retifanlimab 500 mg IV; * Dose Level 2A: Trametinib 2 mg PO, Ruxolitinib 10 mg PO, Retifanlimab 500 mg IV; * Dose Level 3A: Trametinib 2 mg PO, Ruxolitinib 15 mg PO, Retifanlimab 500 mg IV. |
| Part 1 Schedule B: TR^2 Alternate Schedule | EXPERIMENTAL | Participants in this group will receive the MTD determined in Part 1 Schedule A on a continuous dosing cycle: Trametinib and Ruxolitinib on Days 1-28 and Retifanlimab on Day 8 of a 28-Day Cycle. |
| Part 2: TR^2 Expansion Cohort | EXPERIMENTAL | Participants in this group will receive Trametinib, Ruxolitinib and Retifanlimab at the most appropriate dose and schedule determined in Part 1. Participants will continue to receive treatment as long as receiving clinical benefit or until disease progression. |
| Name | Type | Description |
|---|---|---|
| Trametinib | DRUG | Trametinib will be administered orally once daily via tablet. |
| Ruxolitinib | DRUG | Ruxolitinib will be administered orally twice daily (BID) via tablet. |
| Retifanlimab | DRUG | Retifanlimab will be administered intravenously (IV) on Day 8 of a 28-day cycle.. |
Inclusion Criteria: 1. Histologically confirmed, metastatic pancreatic adenocarcinoma. Patients with adenosquamous carcinoma and mixed adenocarcinoma/neuroendocrine carcinoma (MANEC) of the pancreas are eligible, but pure neuroendocrine neoplasms are excluded. 2. Progression of disease or intoleran...
Trametinib is being studied for the treatment of Pancreatic Ductal Adenocarcinoma, specifically in metastatic cases. It is an investigational small molecule in Phase 1 clinical development. The drug is being evaluated in combination with other agents, including MEK, STAT3, and PD-1 inhibitors, to assess its potential efficacy in this patient population.
Trametinib targets the MEK protein, which is part of the RAS-RAF-MEK-ERK signaling pathway involved in cell growth and proliferation. By inhibiting MEK, Trametinib aims to disrupt this pathway, which is often dysregulated in cancers such as Pancreatic Ductal Adenocarcinoma. This mechanism is being explored in combination with STAT3 and PD-1 inhibitors.
Trametinib is being developed by Incyte Corporation, a biopharmaceutical company traded on NASDAQ under the ticker INCY. The company is conducting clinical research to evaluate the drug's safety and efficacy in Pancreatic Ductal Adenocarcinoma. Incyte is responsible for the ongoing development and regulatory activities for this investigational therapy.
Trametinib is in Phase 1 clinical development for Pancreatic Ductal Adenocarcinoma. It is an investigational drug, meaning it has not yet been approved by regulatory authorities. The Phase 1 trial has been completed, with results expected to inform further development. The drug is not yet available for commercial use.
Trametinib is being studied in a Phase 1 clinical trial with the identifier NCT05440942, titled "Combined MEK, STAT3 and PD-1 Inhibition in Metastatic Pancreatic Ductal Adenocarcinoma." This completed trial enrolled 28 participants in the United States, with a minimum age of 18 years. The study was controlled but not randomized or double-blinded.
Trametinib is the generic name for the drug also known as Mekinist. In the context of this development program, Incyte Corporation is studying Trametinib for Pancreatic Ductal Adenocarcinoma. The drug is being evaluated in combination with other inhibitors, and it is important to note that it is still investigational for this indication.