Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication XOLREMDI is indicated in patients 12 years of age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections and myelokathexis) to increase the number of circulating mature neutrophils and lympocytes. FDA label
Also known as X4P-001, AMD11070
Mavorixafor · 9 trials · 10 indications
Positive ANC response: Increase of ANC \>500 cells/microliter (µL) from baseline.
AUCANC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The absolute neutrophil count (ANC) clinically meaningful threshold was defined as ANC ≥ 600/microliter (μL).
AUCANC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The ANC clinically meaningful threshold was defined as ANC ≥ 600/μL. Data for this outcome measure are reported as an "All Visits" summary based on the mean of AUCs that is, the per-participant average of the AUCANC across the 3 visits where participant was treated with at least 300/400 mg dose. Time frame reported is based on data collection time points.
AUCALC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The absolute lymphocyte count (ALC) clinically meaningful threshold was defined as ALC ≥ 1000/μL.
AUCALC was collected over a 24-hour period above clinically meaningful thresholds for the mavorixafor-treated participants over 6 months. The ALC clinically meaningful threshold was defined as ALC ≥ 1000/μL. Data for this outcome measure are reported as an "All Visits" summary based on the mean of AUCs that is, the per-participant average of the AUCALC across the 3 visits where participant was treated with at least 300/400 mg dose. Time frame reported is based on data collection time points.
An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. Adverse events with onset after administration of the first dose of study drug up to 10 days after last dosing date were considered TEAEs. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
| Arm | Type | Description |
|---|---|---|
| Mavorixafor | EXPERIMENTAL | Participants will receive mavorixafor orally once daily starting from Day 1 through Week 52. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo to match mavorixafor orally once daily starting from Day 1 through Week 52. |
| X4P-001 | EXPERIMENTAL | Initial Treatment Phase: Participants will initiate treatment with mavorixafor at 50 milligrams (mg) once daily (QD) orally or a higher dose, with potential escalation based on area under the curve for absolute neutrophil count and absolute leukocyte count (AUCANC/ALC) values to a maximum total daily dose of 400 mg. Participants are expected to receive treatment for 24 weeks in the initial Treatment Period or until development of a treatment-limiting toxicity (TLT). Extension Phase: All participants will receive mavorixafor; the dose will not exceed 400 mg. In the Extension Phase, treatment may continue until mavorixafor becomes available via an alternative mechanism (for example, drug is commercially available, an expanded access program, etc.) or until the study is terminated by the sponsor. |
| Dose Escalation (Part A): X4P-001 200 mg BID with Axitinib | EXPERIMENTAL | Participants will receive X4P-001 200 milligrams (mg) orally twice daily (BID) with axitinib at 5 mg orally BID. |
| Dose Escalation (Part A): X4P-001 400 mg QD with Axitinib | EXPERIMENTAL | Participants will receive X4P-001 400 mg orally once daily (QD) with axitinib at 5 mg orally BID. |
| Dose Escalation (Part A): X4P-001 600 mg QD with Axitinib | EXPERIMENTAL | Participants will receive X4P-001 600 mg orally QD with axitinib at 5 mg orally BID. |
| Dose Expansion (Part B): X4P-001 400 mg QD With Axitinib | EXPERIMENTAL | Participants received X4P-001 400 mg orally QD with axitinib at 5 mg orally BID. |
| Dose Escalation and Expansion (Part C): X4P-001 600 mg QD Monotherapy | EXPERIMENTAL | Participants will receive X4P-001 600 mg orally QD. |
| Group 1: Child-Pugh A | EXPERIMENTAL | Participants with mild HI will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period. |
| Group 2: Child-Pugh B | EXPERIMENTAL | Participants with moderate HI will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period. |
| Group 3: Child-Pugh C | EXPERIMENTAL | Participants with severe HI will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period. |
| Group 4: HVs | EXPERIMENTAL | HVs matched with the mild HI participants will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period. |
| Group 5: HVs | EXPERIMENTAL | HVs matched with the moderate HI participants will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period. |
| Group 6: HVs | EXPERIMENTAL | HVs matched with the severe HI participants will receive a single dose of mavorixafor orally on an empty stomach, following a minimum 10-hour fasting period. |
| Mavorixafor and Ibrutinib | EXPERIMENTAL | Each participants will initially receive mavorixafor at Dose Level 1 (200 mg QD) in combination with ibrutinib 420 mg. Cohort A will comprise the first 6 participants enrolled in the study that complete at least their first cycle at Dose Level 2 (400 mg QD). Cohort A participants will start at Dose Level 1 and be allowed to dose escalate after the first cycle to Dose Level 2, if no DLTs are observed during the first cycle of each participant. Cohort B will comprise the next 6 participants enrolled into the study that complete at least their 1st cycle at Dose Level 3 (600 mg QD). Cohort B participants will start at Dose Level 1 and be allowed to dose escalate up to Dose Levels 2 and 3. Cohort C will comprise the remainder of participants enrolled up to the total of 18. Cohort C participants will start at Dose Level 1 and be allowed to escalate to 400 and 600 mg after each dose level has been deemed safe by participants from Cohort A and B. |
| X4P-001 + Pembrolizumab | EXPERIMENTAL | X4P-001 alone, then adding pembrolizumab |
| Name | Type | Description |
|---|---|---|
| Mavorixafor | DRUG | Mavorixafor will be administered per schedule specified in the arm description. |
| Placebo | DRUG | Placebo will be administered per schedule specified in the arm description. |
| X4P-001 | DRUG | Mavorixafor will be provided as either 25 mg or 100 mg capsules. |
| axitinib | DRUG | Continuous, oral dosing |
| Ibrutinib | DRUG | Ibrutinib capsules will be administered per dose and schedule specified in the arm. |
| Pembrolizumab | DRUG | Pembrolizumab 2 mg/kg, administered by IV infusion every 3 weeks |
Key Inclusion Criteria: * Diagnosis of congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorder ≥6 months prior to the screening visit that is not attributable to medications, active or recent infections or malignancy. * Congenital Neutropenia, including but not limited...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| X4 Pharmaceuticals, Inc. | XFOR | 1 | PHASE3 | Mavorixafor |
Mavorixafor is an investigational small molecule CXCR4 antagonist developed by X4 Pharmaceuticals for hematologic conditions. It is being studied in chronic neutropenia disorders, WHIM syndrome, Waldenstrom's macroglobulinemia, and hepatic insufficiency. It is an oral therapy in clinical development and holds FDA Fast Track designation.
Mavorixafor targets CXCR4, a chemokine receptor, and acts as a CXCR4 antagonist. By blocking this receptor, mavorixafor is designed to mobilize white blood cells from the bone marrow into circulation. This mechanism underlies its study in neutropenia disorders and in Waldenstrom's macroglobulinemia, where CXCR4 mutations affect disease biology.
Mavorixafor is developed by X4 Pharmaceuticals, Inc., which trades under the ticker XFOR. The company is advancing the drug across multiple hematology programs, including chronic neutropenia disorders and Waldenstrom's macroglobulinemia, and holds FDA Fast Track designation for the asset.
Mavorixafor is in Phase 2 development for acquired primary autoimmune and idiopathic chronic neutropenia disorders, with a Phase 2 study not yet recruiting. A Phase 3 trial in congenital and acquired chronic neutropenic disorders is recruiting, and Phase 1 studies in hepatic impairment and Waldenstrom's macroglobulinemia have been completed. Mavorixafor is investigational and not approved.
Mavorixafor trials include NCT06056297, a recruiting Phase 3 study in chronic neutropenic disorders with recurrent or serious infections, and NCT07902830, a Phase 2 study of G-CSF dose reduction in acquired neutropenia that is not yet recruiting. Completed studies include NCT06858696 in hepatic impairment and NCT04274738 in Waldenstrom's macroglobulinemia.
Mavorixafor was studied in Waldenstrom's macroglobulinemia in combination with ibrutinib in participants whose tumors express MYD88 and CXCR4 mutations. That Phase 1 trial, NCT04274738, has been completed. The program targets patients whose CXCR4 mutation status may influence response to treatment.