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Also known as Zumsemetinib, ATI-450
Zunsemetinib · 5 trials · 6 indications
Participants achieving American College of Rheumatology (ACR) 20 (responders) were defined as having ≥20% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥20% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician's Global Assessment of Disease Activity (VAS), and acute phase reactant as measured by hsCRP. Model-based estimates and 95% confidence intervals (CIs) were produced.
AN count was the sum of number of abscess and inflammatory nodules across anatomical regions. The least square (LS) mean change from baseline in the count at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model.
Safety and tolerability reported as Adverse Events (AEs). AEs will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. AEs will be presented by system organ class and preferred term in frequency tables.
| Arm | Type | Description |
|---|---|---|
| ATI-450 20 mg BID plus Methotrexate | EXPERIMENTAL | ATI-450 20 mg oral tablet twice daily (BID) with a stable weekly dose of methotrexate for 12 weeks |
| ATI-450 50 mg BID plus Methotrexate | EXPERIMENTAL | ATI-450 50 mg oral tablet BID with a stable weekly dose of methotrexate for 12 weeks |
| Placebo plus Methotrexate | PLACEBO_COMPARATOR | Placebo oral tablet BID with a stable weekly dose of methotrexate for 12 weeks |
| ATI-450 | EXPERIMENTAL | ATI-450 50 milligrams (mg) oral tablet twice daily (BID) |
| Placebo | EXPERIMENTAL | Placebo oral tablet BID |
| ATI-450 plus Methotrexate | EXPERIMENTAL | ATI-450 50mg oral tablet BID with a stable weekly dose of Methotrexate |
| Dose escalation phase (zunsemetinib + mFOLFIRNOX) | EXPERIMENTAL | The dose of zunsemetinib will be determined by the dose level assigned and will be taken by mouth either once or twice daily depending on assigned dose level. mFOLFIRINOX will be 85 mg/m\^2 of oxaliplatin intravenous (IV) on day 1 of each cycle, 150 mg/m\^2 of irinotecan IV on day 1 of each cycle, 400 mg/m\^2 of leucovorin IV on day 1 of each cycle, and 2400 mg/m\^2 continuous infusion starting on day 1 of each cycle and continuing for 46 hours. Each cycle is 2 weeks in length. |
| Dose expansion phase (zunsemetinib + mFOLFIRNOX) | EXPERIMENTAL | The dose of zunsemetinib will be determined during the dose escalation phase of the trial. mFOLFIRINOX will be 85 mg/m\^2 of oxaliplatin intravenous (IV) on day 1 of each cycle, 150 mg/m\^2 of irinotecan IV on day 1 of each cycle, 400 mg/m\^2 of leucovorin IV on day 1 of each cycle, and 2400 mg/m\^2 continuous infusion starting on day 1 of each cycle and continuing for 46 hours. Each cycle is 2 weeks in length. |
| 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 |
|---|---|---|
| ATI-450 50 mg oral tablet BID | DRUG | Oral, small molecule MK2 inhibitor |
| Placebo oral tablet | DRUG | Placebo tablet manufactured to match ATI-450 in appearance |
| Methotrexate | DRUG | 15 mg to 25 mg weekly |
| ATI-450 20 mg oral tablet BID | DRUG | Oral, small molecule MK2 inhibitor |
| ATI-450 | DRUG | Oral, small molecule MK2 inhibitor |
| Zunsemetinib | DRUG | Patients should take zunsemetinib approximately 12 hours apart (if twice daily dosing) or 24 hours apart (if once daily dosing) at the same time(s) every day, with 8 oz of water. |
| mFOLFIRINOX | DRUG | Includes oxaliplatin, irinotecan, leucovorin, and 5-FU. |
| 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: * Able to comprehend and be willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved participant ICF prior to administration of any study-related procedures. * Diagnosis of adult-onset RA as defined by the 2010 American College of Rheumato...
Zunsemetinib is an investigational small molecule kinase inhibitor being developed by Aclaris Therapeutics, Inc. (ticker: ACRS) for oncology indications. It is a Phase 1 candidate being studied in hormone receptor positive HER-2 negative metastatic breast cancer and metastatic pancreatic ductal adenocarcinoma. It is not yet approved for any indication.
Zunsemetinib targets MAPKAPK2, also known as MK2, a kinase. It belongs to the -tinib kinase inhibitor class. By inhibiting MAPKAPK2, the drug is designed to interfere with signaling pathways relevant to tumor progression, and it is being evaluated in biomarker-selected patient populations.
Zunsemetinib is being studied for two oncology indications: hormone receptor positive HER-2 negative metastatic breast cancer with bone metastasis, and metastatic pancreatic ductal adenocarcinoma. Both uses are investigational and are being tested in Phase 1 clinical trials in combination with other therapies.
Zunsemetinib is developed by Aclaris Therapeutics, Inc., which trades under the ticker ACRS. Aclaris is the sponsor of the clinical program evaluating the drug in metastatic breast cancer and metastatic pancreatic ductal adenocarcinoma.
Zunsemetinib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA for any indication. The Phase 1 program includes one active, recruiting trial, with no completed trials to date.
Zunsemetinib is being evaluated in two recruiting Phase 1 trials. NCT06374459 studies it with capecitabine in hormone receptor positive HER-2 negative metastatic breast cancer with bone metastasis, enrolling 152 patients. NCT06648434 studies it with mFOLFIRINOX in untreated metastatic pancreatic ductal adenocarcinoma, enrolling 51 patients.
Yes, Zumsemetinib is an alternative spelling of Zunsemetinib. Both names refer to the same investigational MAPKAPK2 inhibitor developed by Aclaris Therapeutics, Inc. (ticker: ACRS) for hormone receptor positive HER-2 negative metastatic breast cancer and metastatic pancreatic ductal adenocarcinoma.