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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT06374459 | Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis | PHASE1 | RECRUITING | 152 | — | — | Jan 30, 2025 | May 31, 2032 | Apr 20, 2026 | 3 | United States |
| Arm | Type | Description |
|---|---|---|
| Phase Ib: Zunsemetinib + Capecitabine | EXPERIMENTAL | Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose along with capecitabine (1000 mg/m\^2 PO BID on Days 1-14 an every 21-day cycle). For patients enrolled in phase Ib, capecitabine is dosed on days 2-15 during cycles 1-2. Dose escalation of zunsemetinib will utilize a 3+3 design. A maximum of 3 dose levels of zunsemetinib will be tested, and the two highest dose levels which did not lead to more than 1 of 6 patients with DLT in cycle 1 will be chosen as the RP2D-L1 and RP2D-L2 for Phase II. If only one dose level of zunsemetinib was found tolerable, then only one RP2D will be chosen for Phase II. |
| Phase II Arm 1: Standard of care anti-resorptive + Capecitabine | ACTIVE_COMPARATOR | Standard of care anti-resorptives will consist of bisphosphonate (zoledronic acid) is to be administered every 4-12 weeks, or denosumab is to be administered every 4-6 weeks, as per physician choice and institutional practice. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. |
| Phase II Arm 2: Zunsemetinib (RP2D-L1) + Capecitabine | EXPERIMENTAL | Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. |
| Phase II Arm 3: Zunsemetinib (RP2D-L2) + Capecitabine | EXPERIMENTAL | Patients will receive zunsemetinib by mouth (PO) twice per day (BID) at an assigned dose. In general, capecitabine will be taken twice daily at a dose of 1000 mg/m\^2 on Days 1 through 14 of every 21-day cycle. The first 4 patients enrolling to phase II will take capecitabine on a different schedule for PK purposes in Cycles 1 and 2 ONLY. Patients will take capecitabine at a dose of 1000mg/m\^2 on Days 2 through 15 of Cycles 1 and 2, and then on Days 1 through 14 starting with Cycle 3. If only one dose level of zunsemetinib plus capecitabine was found tolerable in phase Ib testing, the phase II trial will proceed with 2:1 two-arm randomization with Arm 2 of capecitabine plus zunsemetinib and Arm 1 of capecitabine plus standard of care anti-resorptive agent. |
| Name | Type | Description |
|---|---|---|
| Zumsemetinib | DRUG | Patients should take zunsemetinib at approximately the same times every day, with or without food with 8 oz of water. |
| Capecitabine | DRUG | Patients should take capecitabine at approximately the same times every day, within 30 minutes after a meal. |
| Zoledronic acid | DRUG | Standard of care. Will receive zoledronic acid or denosumab. |
| Denosumab | DRUG | Standard of care. Will receive zoledronic acid or denosumab. |
Inclusion Criteria for both Phase Ib and Phase II: * Hormone receptor-positive, HER2-negative metastatic breast cancer. * Measurable or non-measurable but evaluable disease by RECIST v1.1. * Candidate for capecitabine treatment per physician decision. See below phase-specific eligibility criteria f...