Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Momelotinib, MMB, GS-0387, Momelotinib (MMB)
CYT387 · 13 trials · 18 indications
Myelofibrosis Symptom Assessment Form (MFSAF) TSS version (v) 4.0 response rate was defined as percentage of participants with a \>= 50 percent (%) reduction from Baseline in mean MFSAF TSS over consecutive 28-day period immediately before end of Week 24. TSS response rate was measured using MFSAF v4.0. MFSAF v4.0 comprises 7 domains representing 7 most relevant symptoms of myelofibrosis (MF) identified through existing participant and clinician-based evidence: fatigue,night sweats,pruritus,abdominal discomfort,pain under left ribs,early satietyand bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0(absent) to 10(worst imaginable). The MFSAF TSS was calculated as sum of scores of 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date.
Splenic response rate at Week 24 is defined as the percentage of participants who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT.
ORR is defined as the proportion of participants who have achieved complete response (CR) or partial response (PR) during the 26-week Primary Treatment Period.
The maximum tolerated dose (MTD) is defined by a target dose-limiting toxicities (DLT) rate of 30%, assessed during the observation window by a 3+3 design. The 3+3 design will enroll a first cohort of 3 patients at the starting dose of 200 mg/d: * If 0 of the 3 patients at the dose of 200 mg/d experienced a DLT during the first 4-week cycle of momelotinib, the dose will escalate to 300 mg/d for the next cohort. * If 1 of the 3 patients at the dose of 200 mg/d has a DLT, a cohort of three additional patients will be treated at the same dose of 200 mg/d. * If \> 1 patient of the 3 patients at the dose of 200 mg/d have a DLT, the dose will de-escalate to 150 mg/d for the next cohort. The same process will be repeated until reaching the MTD. In total, between 6 and 18 patients will be enrolled during this safety run-in phase.
Determination of overall clinical response rate at 24 weeks after momelotinib initiation on VEXAS related symptoms (including complete (CR) or partial response (PR)) : * CR includes complete disappearance of symptoms related to systemic inflammation according to treating physician and daily dose of steroids ≤ 10 mg/d (equivalent prednisolone). * PR includes complete disappearance of symptoms related to systemic inflammation according to treating physician and reduction of at least 50% of daily dose steroids compared to baseline and/or daily dose of steroids \> 10 mg/d.
RBC-TI defined as not requiring RBC transfusions (except in the case of clinically overt bleeding). Percentage of participants with RBC-TI will be measured for any consecutive 12-week interval over 24-week duration.
TI response is defined as not requiring red blood cell (RBC) transfusion (except in the case of clinically overt bleeding) for any ≥12-week interval.
The percentage of subjects who became transfusion independent for ≥ 12 weeks at any time on study. A subject was considered transfusion independent on study if no RBC transfusion occurred in any 12-week period during the 24-week treatment period.
Long-term safety and tolerability profile of momelotinib based on safety data (adverse events and selected hematology and chemistry laboratory parameters) collected after the first dose of momelotinib in the parent study.
Measured by complete response (CR) rate, partial response (PR) rate and clinical improvement (CI) rate according to IWG-MRT consensus criteria
The Objective Response Rate (ORR), as measured by complete response (CR) rate, partial response (PR) rate and clinical improvement (CI) rate according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) is to be measured at the end of every cycle of therapy.
The pharmacokinetics (PK) of CYT387 in patients with PMF or post-ET/PV MF is to be assessed on Day 1 and Day 28 in Cycle 1 of therapy
| Arm | Type | Description |
|---|---|---|
| Momelotinib | EXPERIMENTAL | Participants will receive momelotinib plus placebo to match danazol |
| Danazol | ACTIVE_COMPARATOR | Participants will receive danazol plus placebo to match momelotinib |
| Arm 1: Momelotinib | EXPERIMENTAL | Participants will receive open-label momelotinib for 24 weeks during the randomized treatment phase, after which they will be eligible to receive momelotinib in an extended treatment phase for up to an additional 204 weeks. |
| Arm 2: Best Available Therapy (BAT) | ACTIVE_COMPARATOR | Participants in the BAT treatment arm will receive open-label treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may be changed at any time during the study except during the screening period. After completion of the randomized treatment phase, participants will be eligible to receive momelotinib for the duration of the study during the extended treatment phase for up to 204 weeks. |
| Ruxolitinib | ACTIVE_COMPARATOR | Participants will receive ruxolitinib plus placebo to match momelotinib. |
| Momelotinib Dose level 1 + Glucocorticoids | EXPERIMENTAL | Participants will receive momelotinib at dose level 1 along with glucocorticoids as a background therapy (prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3. |
| Momelotinib Dose level 2 + Glucocorticoids | EXPERIMENTAL | Participants will receive momelotinib at dose level 2 along with glucocorticoids as a background therapy (prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3 |
| Placebo + Glucocorticoids | PLACEBO_COMPARATOR | Participants will receive momelotinib matched placebo along with glucocorticoids as a background therapy(prednisone or prednisolone). Due to adaptive design of the study, additional participants may be randomized to this arm in phase 3 |
| Momelotinib treatment | EXPERIMENTAL | Patients will receive momelotinib. |
| Momelotinib dose level 1 | EXPERIMENTAL | - |
| Momelotinib dose level 2 | EXPERIMENTAL | - |
| Momelotinib + Luspatercept | EXPERIMENTAL | Participants with transfusion dependent primary myelofibrosis or post- PV/ ET myelofibrosis that is JAKi naïve or JAKi experienced will receive momelotinib and luspatercept. |
| Cohort 1: Study GS-US-352-0101 | OTHER | Participants will continue to receive the same dosage regimen as in the previous MMB study GS-US-352-0101 until MMB receives regulatory approval and is commercially available, or development of the product ceases. |
| Cohort 2: Study GS-US-352-1214 | OTHER | Participants will continue to receive the same dosage regimen as in the previous MMB study GS-US-352-1214 until MMB receives regulatory approval and is commercially available, or development of the product ceases. |
| Cohort 3: Study GS-US-352-1154 | OTHER | Participants will continue to receive the same dosage regimen as in the previous MMB study GS-US-352-1154 until MMB receives regulatory approval and is commercially available, or development of the product ceases.. |
| Cohort 4: Study SRA-MMB-301 | OTHER | Participants will continue to receive the same dosage regimen as in the previous MMB study SRA-MMB-301 until MMB receives regulatory approval and is commercially available, or development of the product ceases. |
| Cohort 1 | EXPERIMENTAL | Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years. |
| Cohort 2 | EXPERIMENTAL | Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years. |
| Cohort 3 | EXPERIMENTAL | Participants previously enrolled in Study GS-US-354-0101 will receive momelotinib for up to 4 years. Cohort 3 was closed and all enrolled participants were discontinued from this study because parent Study GS-US-354-0101 was terminated. |
| Cohort 4 | EXPERIMENTAL | Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years. |
| CYT387 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Momelotinib | DRUG | Momelotinib tablets will be self-administered orally once daily |
| Placebo to match danazol | DRUG | Danazol placebo capsules will be self-administered orally twice daily |
| Danazol | DRUG | Danazol capsules will be self-administered orally twice daily |
| Placebo to match momelotinib | DRUG | Momelotinib placebo tablets will be self-administered orally once daily |
| Best Available Therapy (BAT) | DRUG | Regimens for BAT may include but are not limited to chemotherapy (eg hydroxyurea), anagrelide, corticosteroid, hematopoietic growth factor, immunomodulating agent, androgen, interferon, and may include no myelofibrosis treatment. |
| Ruxolitinib | DRUG | Ruxolitinib tablets administered orally twice daily |
| Placebo to match ruxolitinib | DRUG | Placebo to match ruxolitinib tablets administered orally twice daily |
| Glucocorticoids | DRUG | Glucocorticoids (prednisone or prednisolone) will be administered |
| Placebo | DRUG | Placebo will be administered |
| Momelotinib treatment | DRUG | Patients included will receive momelotinib continuously until disease progression or loss of response, at physician's discretion. |
| Luspatercept | DRUG | Luspatercept will be administered subcutaneously. |
| MMB | DRUG | Tablet(s) administered orally once daily |
| CYT387 | DRUG | For the Part 1 dose-escalation portion of the study, patients will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 100 mg/day. CYT387 will be orally self-administered as a single daily dose beginning on Day 1 of the study, and thereafter at approximately the same time each day of the 28-day cycle. It is recommended that all doses be preceded by a 2-hour fast from food and beverages, and be followed by a 1-hour post-dose fast from food and beverages. Twenty additional patients will be assigned to a 150 mg BID (twice daily) dosing schedule. CYT387 will be orally self-administered twice-daily with doses approximately 10-12 hours apart beginning on Day 1 of the study, and thereafter at approximately the same times each day of the 28-day cycle. For the Part 2 dose confirmation portion of the study, patients will be assigned to either 150 mg or 300 mg QD (once daily) dose groups. |
Inclusion Criteria: * Age \>= 18 years. * Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post- polycythemia vera/essential thrombocythemia (PV/ET) MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Tre...
CYT387 is an investigational small molecule being studied for the treatment of Primary Myelofibrosis, as well as Post-Polycythemia Vera Myelofibrosis and Post-Essential Thrombocythemia Myelofibrosis. It is a targeted therapy designed to address the underlying disease process in these myeloproliferative conditions.
CYT387 is being developed by GSK plc, a global biopharmaceutical company listed on the stock exchange under the ticker symbol GSK. The company is conducting clinical research to evaluate the safety and efficacy of this investigational drug in patients with myelofibrosis.
CYT387 is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities and is still undergoing clinical trials to assess its safety and effectiveness in patients with Primary Myelofibrosis and related conditions.
CYT387 has been studied in one completed clinical trial, registered as NCT00935987. This Phase 1 study evaluated the safety and efficacy of CYT387 in patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis, enrolling 166 participants across the United States, Australia, and Canada.
Yes, CYT387 is also known as momelotinib. This alternative name is used in scientific literature and clinical trial registries to refer to the same investigational drug being developed by GSK plc for the treatment of myelofibrosis.