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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05440942 | Combined MEK, STAT3 and PD-1 Inhibition in Metastatic Pancreatic Ductal Adenocarcinoma | PHASE1 | COMPLETED | 28 | — | — | Jan 19, 2023 | May 30, 2025 | Jun 5, 2025 | 1 | United States |
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...