Claims for Patent: 11,883,375

Summary for Patent: 11,883,375

Title:	Mirdametinib treatment
Abstract:	The present disclosure relates to a method for treating certain types of tumors or cancers, such as plexiform neurofibromas (PN), plexiform neurofibromas associated with neurofibromatosis type 1 (NF1-PN), by orally administering an effective amount of mirdametinib to the patient, where an amount of mirdametinib is administered on the first day of treatment to provide (i) an AUC0-tau less than 400 ng h/mL, (ii) a Cmax no more than 40 ng/mL, or (iii) both.
Inventor(s):	Uchenna H Iloeje, Abraham J Langseth, Todd Shearer
Assignee:	SpringWorks Therapeutics Inc
Application Number:	US18/334,518
Patent Claims:	1. A method of treating a human patient 2 years or older who has neurofibromatosis type 1 (NF1) associated inoperable plexiform neurofibromas (PN) comprising orally administering an effective amount of mirdametinib to the patient, wherein (I) an amount of mirdametinib is administered on the first day of treatment to provide an AUC0-tau less than 300 ng·h/mL; and (II) (a) for a patient having a body surface area no more than 0.69 m2, the patient is initially administered 1 mg mirdametinib, (b) for a patient having a body surface area of 0.7 to 1.04 m2, the patient is initially administered 2 mg mirdametinib, or (c) for a patient having a body surface area of 1.05 to 1.49 m2, the patient is initially administered 3 mg mirdametinib. 2. The method of claim 1, wherein the patient has symptomatic, inoperable plexiform neurofibromas. 3. A method of treating a human patient 2 years or older who has neurofibromatosis type 1 (NF1) associated inoperable plexiform neurofibromas (PN) that is progressing or causing significant morbidity comprising orally administering an effective amount of mirdametinib to the patient, wherein (I) an amount of mirdametinib is administered on the first day of treatment to provide an AUC0-tau less than 400 ng·h/mL; and (II) (a) for a patient having a body surface area no more than 0.69 m2, the patient is initially administered 1 mg mirdametinib twice daily, (b) for a patient having a body surface area of 0.7 to 1.04 m2, the patient is initially administered 2 mg mirdametinib twice daily, and (c) for a patient having a body surface area of 1.05 to 1.49 m2, the patient is initially administered 3 mg mirdametinib twice daily. 4. The method of claim 1, wherein an amount of mirdametinib is administered on the first day of treatment to provide an AUC0-tau less than 200 ng·h/mL. 5. The method of claim 1, wherein an amount of mirdametinib is administered on the first day of treatment to provide an AUC0-tau less than 100 ng·h/mL. 6. The method of claim 1, wherein the patient has progressive PN. 7. The method of claim 1, wherein the patient has PNs that cause significant morbidity. 8. The method of claim 1, wherein the patient has head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity or are significantly disfiguring, lesions of the extremity that cause limb hypertrophy or loss of function, or painful lesions. 9. The method of claim 8, wherein the lesions causing major deformity or are significantly disfiguring are tumors of the head and neck or those on other areas of the body that are unable to be concealed by standard garments. 10. The method of claim 1, wherein the patient has the clinical diagnosis of NF1 using the NIH Consensus Conference and one or more of the following: (a) six or more café-au-lait macules with a diameter>5 mm in prepubertal and >15 mm in post-pubertal individuals; (b) freckling in axilla or inguinal regions; (c) optic glioma; (d) two or more Lisch nodules; (e) a distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia of thinning of long bone cortex); and (f) a first degree relative with NF1. 11. The method of claim 1, wherein the patient either (a) has a parent diagnosed with NF1 and one or more criteria of (1) through (7) or (b) does not have a parent diagnosed with NF1 but has two or more criteria of (1) through (7): (1) six or more café-au-lait macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals; (2) freckling in the axillary or inguinal region; (3) two or more neurofibromas of any type or one plexiform neurofibroma (4) optic pathway glioma; (5) two or more iris Lisch nodules identified by slit lamp examination or two or more choroidal abnormalities (defined as bright, patchy nodules imaged by optical coherence tomography (OCT)/near-infrared reflectance (NIR) imaging; (6) a distinctive osseus lesion (such as sphenoid dysplasia, anterolateral bowing of the tibia, or pseudarthrosis of a long bone); and (7) a heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue such as white blood cells. 12. The method of claim 1, wherein over each four week period, the mirdametinib is administered for the first three weeks and discontinued for the last one week. 13. The method of claim 1, wherein the patient has at least a 20% reduction in plexiform neurofibroma volume as determined by volumetric magnetic resonance imaging analysis following treatment with mirdametinib. 14. The method of claim 1, wherein the treatment results in decreased pain intensity. 15. The method of claim 1, wherein the treatment results in decreased pain interference. 16. The method of claim 1, wherein the dose administered is reduced due to an adverse event, wherein the dose is reduced as follows: (a) if the dose at the time of the event is 1 mg mirdametinib twice daily, then the reduced daily dose is 1 mg administered in the morning only; (b) if the dose at the time of the event is 2 mg mirdametinib twice daily, then the reduced daily dose is 2 mg administered in the morning and 1 mg administered in the afternoon or evening; and (c) if the dose at the time of the event is 3 mg mirdametinib twice daily, then the reduced daily dose is 2 mg administered twice daily. 17. The method of claim 16, wherein the adverse event resulting in the dose reduction is acneiform. 18. The method of claim 17, wherein, during treatment, the patient is topically administered clindamycin to treat the acneiform. 19. The method of claim 1, wherein the patient is 2 to 15 years of age. 20. The method of claim 1, wherein the patient has a body surface area no more than 0.69 m2 and is initially administered 1 mg mirdametinib. 21. The method of claim 20, wherein the patient is initially administered 1 mg mirdametinib twice daily. 22. The method of claim 1, wherein the patient has a body surface area of 0.7 to 1.04 m2 and is initially administered 2 mg mirdametinib. 23. The method of claim 22, wherein the patient is initially administered 2 mg mirdametinib twice daily. 24. The method of claim 1, wherein the patient has a body surface area of 1.05 to 1.49 m2 and is initially administered 3 mg mirdametinib. 25. The method of claim 24, wherein the patient is initially administered 3 mg mirdametinib twice daily. 26. The method of claim 1, wherein (a) for a patient having a body surface area no more than 0.69 m2, the patient is initially administered 1 mg mirdametinib twice daily, (b) for a patient having a body surface area of 0.7 to 1.04 m2, the patient is initially administered 2 mg mirdametinib twice daily, and (c) for a patient having a body surface area of 1.05 to 1.49 m2, the patient is initially administered 3 mg mirdametinib twice daily. 27. A method of treating a human patient 2 years or older who has neurofibromatosis type 1 (NF1) associated inoperable plexiform neurofibromas (PN) and a body surface area no more than 0.69 m2 comprising orally administering on the first day of treatment 1 mg of mirdametinib to the patient to achieve an AUC0-tau less than 300 ng·h/mL. 28. The method of claim 27, wherein the patient is initially administered 1 mg mirdametinib twice daily. 29. A method of treating a human patient 2 years or older who has neurofibromatosis type 1 (NF1) associated inoperable plexiform neurofibromas (PN) and a body surface area of 1.05 to 1.49 m2 comprising orally administering on the first day of treatment 3 mg of mirdametinib to the patient to achieve an AUC0-tau less than 300 ng·h/mL. 30. The method of claim 29, wherein the patient is initially administered 3 mg mirdametinib twice daily.