IP Library › Granted Patent US 12,667,560
Granted Patent B2
US 12,667,560 · App. 17/995,002 · Granted Jun 30, 2026

Co-administration of mirdametinib and lifirafenib for use in treating cancers

Inventors: Lusong Luo (San Mateo, CA); Zhiyu Tang (San Mateo, CA); Badreddin Edris (Stamford, CT); Todd Webster Shearer (Stamford, CT)
Assignees: SPRINGWORKS THERAPEUTICS, INC.; BEIGENE, LTD.
A61K31/4375A61K9/4858A61K9/4866A61K31/166A61P11/00A61P35/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,667,560
App. No.
17/995,002
Granted
Jun 30, 2026
Kind
B2
Abstract

The present disclosure relates to methods of treating cancers comprising coadministration of mirdametinib or a pharmaceutically acceptable salt form thereof, and lifirafenib or a pharmaceutically acceptable salt form thereof, to a patient in need thereof. Also disclosed are pharmaceutical compositions of mirdametinib or a pharmaceutically acceptable salt form thereof, and lifirafenib or a pharmaceutically acceptable salt form thereof, for use in such cancer treatment, as well as uses of these compounds for manufacture of medicaments for the treatment of cancers.

Claims (21)

1 . A method of treating a patient having a solid tumor comprising co-administering to the patient a therapeutically effective amount of mirdametinib or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of lifirafenib, or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein the therapeutically effective amount of mirdametinib is about 1 mg to about 5 mg per day.

3 . The method of claim 1 , wherein the therapeutically effective amount of lifirafenib, or a pharmaceutically acceptable salt thereof, is about 5mg to about 40 mg per day.

4 . The method of claim 1 , wherein mirdametinib is administered once per day.

5 . The method of claim 1 , wherein lifirafenib, or a pharmaceutically acceptable salt thereof, is administered once per day.

6 . The method of claim 1 , wherein the solid tumor is selected from the group consisting of malignant peripheral nerve sheath tumor, biliary tract cancer, breast cancer, cholangiocarcinoma, urothelial cancer, uterine neoplasm, lung adenocarcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, gastric cancer, sarcoma, bladder cancer, head and neck cancer, small cell lung cancer, endometrial cancer, esophageal cancer, adenoid cystic carcinoma, gallbladder cancer, colorectal cancer, thyroid cancer, hepatocellular cancer, prostate cancer, oral cancer, cervical cancer, pancreatic carcinoma, ovarian cancer, melanoma, and serous carcinoma to the peritoneum.

7 . The method of claim 6 , wherein the patient has non-small cell lung cancer.

8 . The method of claim 6 , wherein the patient has endometrial cancer.

9 . The method of claim 6 , wherein the patient has ovarian cancer.

10 . The method of claim 9 , where the patient has low grade serous ovarian cancer.

11 . A pharmaceutical composition comprising:

a) mirdametinib, or a pharmaceutically acceptable salt thereof;

b) lifirafenib, or a pharmaceutically acceptable salt thereof;

c) optionally a filler;

d) optionally a disintegrant; and

e) optionally a lubricant.

12 . The pharmaceutical composition of claim 11 , wherein mirdametinib is present at about 0.8 mg to about 1.2 mg.

13 . The pharmaceutical composition of claim 11 , wherein mirdametinib is present at about 1.5 mg to about 2.5 mg.

14 . The pharmaceutical composition of claim 11 , comprising a filler, a disintegrant, and a lubricant.

15 . The pharmaceutical composition of claim 14 , wherein mirdametinib is present at about 0.8 mg to about 1.2 mg.

16 . The pharmaceutical composition of claim 14 , wherein mirdametinib is present at about 1.5 mg to about 2.5 mg.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2023
From: EDRIS, BADREDDIN; SHEARER, TODD WEBSTER
To: SPRINGWORKS THERAPEUTICS, INC.
Reel/Frame 063599/0110 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2023
From: LUO, LUSONG; TANG, ZHIYU
To: BEIGENE, LTD.
Reel/Frame 063599/0193 →
Continuity (2)
Provisional Application 63005153 · Apr 3, 2020
Related Publication 20230128315A1 · Apr 27, 2023
References Cited (68)
US 6960614B2 · Barrett et al. · 2005 [cited by applicant]
US 7060856B2 · Macikenas et al. · 2006 [cited by applicant]
US 7411001B2 · Barrett et al. · 2008 [cited by applicant]
US 10351559B2 · Zhang et al. · 2019 [cited by applicant]
US 11066358B1 · Irdam · 2021 [cited by applicant]
US 11084780B1 · Patterson et al. · 2021 [cited by applicant]
US 12324791B2 · Iloeje et al. · 2025 [cited by applicant]
US 20140155372A1 · Lee et al. · 2014 [cited by applicant]
US 20160355510A1 · Springer et al. · 2016 [cited by applicant]
US 20220257543A1 · Patterson et al. · 2022 [cited by applicant]
US 20230293465A1 · Baker et al. · 2023 [cited by applicant]
EP 3560516A1 · 2019 [cited by applicant]
WO WO0200213A1 · 2002 [cited by applicant]
WO WO0206213A2 · 2002 [cited by applicant]
WO WO2004045617A1 · 2004 [cited by applicant]
WO WO2005040098A1 · 2005 [cited by applicant]
WO WO2006061712A2 · 2006 [cited by applicant]
WO WO2006134469A1 · 2006 [cited by applicant]
WO WO2007042885A2 · 2007 [cited by applicant]
WO 2019051296A1 · 2019 [cited by applicant]
WO 2019113345A1 · 2019 [cited by applicant]
WO 2020055760A1 · 2020 [cited by applicant]
WO WO2021202981A1 · 2021 [cited by applicant]
Roskoski, Pharmacological Research (2018), 135, p. 239-258. [cited by examiner]
Berge, S.M., et al., “Pharmaceutical Salts,” Journal of Pharmaceutical Sciences 66(1):1-19, Elsevier, United States (Jan. 1977). [cited by applicant]
Borght, K.V.D., et al., “BIGL: Biochemically Intuitive Generalized Loewe Null Model for Prediction of the Expected Combined Effect Compatible with Partial Agonism and Antagonism,” Scientific Reports 7(1):17935, Nature P… [cited by applicant]
Chapman, P.B., et al., “Improved Survival with Vemurafenib in Melanoma With BRAF V600E Mutation,” The New England Journal of Medicine 364(26):2507-2516, Massachusetts Medical Society, United States (Jun. 2011). [cited by applicant]
Dombi, E., et al., “NF1 Plexiform Neurofibroma Growth Rate by Volumetric MRI: Relationship to Age and Body Weight,” Neurology 68(9):643-647, Lippincott Williams & Wilkins, United States (Feb. 2007). [cited by applicant]
Flaherty, K.T., et al., “Improved Survival With MEK Inhibition in BRAF-mutated Melanoma,” The New England Journal of Medicine 367(2):107-114, Massachusetts Medical Society, United States (Jul. 2012). [cited by applicant]
Flaherty, K.T., et al., “Combined BRAF and MEK Inhibition in Melanoma with Braf V600 Mutations,” The New England Journal of Medicine 367(18):1694-1703, Massachusetts Medical Society, United States (Nov. 2012). [cited by applicant]
Florence, A. J., “Polymorph screening in pharmaceutical development,” European Pharmaceutical Review, Issue 4, accessed at URL: [https://www.europeanpharmaceuticalreview.com/article/3659/polymorph-screening-inpharmaceut… [cited by applicant]
Hauschild, A., et al., “Dabrafenib in BRAF-mutated Metastatic Melanoma: A Multicentre, Open-label, Phase 3 Randomised Controlled Trial,” Lancet 380(9839):358-365, Elsevier, United Kingdom (Jul. 2012). [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/018373, European Patent Office, Netherlands, mailed on Dec. 8, 2021, 17 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/018378, European Patent Office, Netherlands, mailed on Nov. 12, 2021, 11 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/018381, European Patent Office, Netherlands, mailed on Dec. 8, 2021, 22 pages. [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2021/025551, European Patent Office, Netherlands, mailed on Jul. 28, 2021, 09 pages. [cited by applicant]
Kwong, L.N., et al., “Co-clinical Assessment Identifies Patterns of BRAF Inhibitor Resistance in Melanoma,” The Journal of Clinical Investigation 125(4):1459-1470, American Society for Clinical Investigation, United Sta… [cited by applicant]
Larkin, J., et al., “Combined Vemurafenib and Cobimetinib in BRAF-mutated Melanoma,” The New England Journal of Medicine 371(20):1867-1876, Massachusetts Medical Society, United States (Nov. 2014). [cited by applicant]
Long, G.V., et al., “Dabrafenib and Trametinib Versus Dabrafenib and Placebo for Val600 BRAF-mutant Melanoma: A Multicentre, Double-blind, Phase 3 Randomised Controlled Trial,” Lancet 386(9992):444-451, Elsevier, United… [cited by applicant]
NCT00147550, “A Multicenter, Open-Label, Noncomparative Phase 1-2 Clinical And Pharmacokinetic Study Of Oral PD 0325901 In Patients With Advanced Cancer,” sponsored by Pfizer, first posted Sep. 7, 2005, accessed at URL:… [cited by applicant]
NCT00174369, “Phase 2 Study Of The MEK Inhibitor PD-0325901 In Patients With Advanced Non-Small Cell Lung Cancer,” sponsored by Pfizer, first posted Sep. 15, 2005, accessed at URL:[ https://clinicaltrials.gov/ct2/show/N… [cited by applicant]
NCT01347866, “A Multi-arm Phase 1 Dose Escalation Study Of The Safety, Pharmacokinetics, And Pharmacodynamics Of The Dual Pi3k/Mtor Inhibitors Pf-04691502 And Pf-05212384 In Combination With Experimental Or Approved Ant… [cited by applicant]
NCT02022982, “Phase I/II Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor PD-0325901 for Patients With KRAS Mutant Non-Small Cell Lung Cancer and Other Solid Tumors,” sponsore… [cited by applicant]
NCT02039336, “Phase I/II Study With the Combination of Dacomitinib and PD-0325901 in Metastatic KRAS Mutation Positive Non-small Cell Lung Cancer,” sponsored by The Netherlands Cancer Institute, first posted Jan. 17, 20… [cited by applicant]
NCT02096471, “A Phase 2 Trial of the MEK Inhibitor PD-0325901 in Adolescents and Adults With NF1-Associated Morbid Plexiform Neurofibromas,” sponsored by University of Alabama at Birmingham, first posted Mar. 26, 2014, … [cited by applicant]
NCT02510001, “A Sequential Phase I Study of MEK1/2 Inhibitors PD-0325901 or Binimetinib Combined With cMET Inhibitor PF-02341066 in Patients With RAS Mutant and RAS Wild Type (With Aberrant c-MET) Colorectal Cancer,” sp… [cited by applicant]
NCT03170206, “Phase I/II Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor Binimetinib (MEK 162) for Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer,” sponsored b… [cited by applicant]
NCT03905148, “A Phase 1b, Open-Label, Dose-escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of a RAF Dimer Inhibitor BGB-283 in Combination With MEK Inhibitor PD-032590… [cited by applicant]
NCT03962543, “A Phase 2b Trial of the MEK 1/2 Inhibitor (MEKi) PD-0325901 in Adult and Pediatric Patients With Neurofibromatosis Type 1 (NF1)-Associated Inoperable Plexiform Neurofibromas (PNs) That Are Causing Signific… [cited by applicant]
Nguyen, R., et al., “Growth Dynamics of Plexiform Neurofibromas: a Retrospective Cohort Study of 201 Patients with Neurofibromatosis 1,” Orphanet Journal of Rare Diseases 7:75, BioMed Central Ltd., United Kingdom (Oct. … [cited by applicant]
Pacifico, M.P., et al., “False Discovery Control for Random Fields,” Journal of the American Statistical Association 99(468):1002-1014, American Statistical Association, United States (Dec. 2011). [cited by applicant]
Prada, C.E., et al., “Pediatric Plexiform Neurofibromas: Impact on Morbidity and Mortality in Neurofibromatosis Type 1,” The Journal of Pediatrics 160(3):461-467, Mosby, United States (Mar. 2012). [cited by applicant]
Rasmussen, S.A., et al., “Mortality in Neurofibromatosis 1: An Analysis Using U.S. Death Certificates,” American Journal of Human Genetics 68(5):1110-1118, Cell Press, United States (May 2001). [cited by applicant]
Reddy, S.M., et al., “Influences of BRAF Inhibitors on the Immune Microenvironment and the Rationale for Combined Molecular and Immune Targeted Therapy,” Current Oncology Reports 18(7):42, Current Science, United States… [cited by applicant]
Rizos, H., et al., “BRAF Inhibitor Resistance Mechanisms in Metastatic Melanoma: Spectrum and Clinical Impact,” Clinical Cancer Research 20(7):1965-1977, American Association for Cancer Research, United States (Apr. 201… [cited by applicant]
Tang, Z., et al., “BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-mutated Colorectal Cancers,” Molecular Cancer Therapeutics 14(10):2187-2197, American Association for Cancer … [cited by applicant]
Tucker, T., et al., “Different Patterns of Mast Cells Distinguish Diffuse From Encapsulated Neurofibromas in Patients With Neurofibromatosis 1,” The Journal of Histochemistry and Cytochemistry 59(6):584-590, SAGE Public… [cited by applicant]
Tucker, T., et al., “Longitudinal Study of Neurofibromatosis 1 Associated Plexiform Neurofibromas,” Journal of Medical Genetics 46(2):81-85, British Medical Association, United Kingdom (Feb. 2009). [cited by applicant]
The United States Pharmacopeia—National Formulary, “941 X-ray Diffraction,” 23rd Edition, NF-18, pp. 1843-1844, The United States Pharmacopeial Convention, United States (1995). [cited by applicant]
Yuan, X., et al., “RAF Dimer Inhibition Enhances the Antitumor Activity of MEK Inhibitors in K-RAS Mutant Tumors,” Molecular Oncology 14(8):1833-1849, John Wiley & Sons, Inc., United States (Aug. 2020). [cited by applicant]
“Springworks Therapeutics Announces Initiation of Phase 1b Clinical Trial of MEK Inhibitor PD-0325901 in Combination with BeiGene's RAF Dimer Inhibitor Lifirafenib in Advanced or Refractory Solid Tumor”, 2019, 2 pages, … [cited by applicant]
Lamba S., et al., “RAF Suppression Synergizes With MEK Inhibition in KRAS Mutant Cancer Cells,” Cell Reports, Sep. 2014, vol. 8, pp. 14751483. [cited by applicant]
Preliminary Prospectus: SpringWorks Therapeutics. Dec. 25, 2019 Sections “Mirdametimib” on p. 126, “Mirdametinib in combination with a RAF dimer inhibitor (lifirafenib)” from p. 133-137, in particular subsections “Precl… [cited by applicant]
Study of the Safety and Pharmacokinetics of BGB-283 (Lifirafenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors, [online], Nov. 1, 2019., [Apr. 2, 2026]https://clinicaltrials.gov… [cited by applicant]
Gupta D., et al., “Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations” Molecules, Jul. 2018, 15 Pages. [cited by applicant]
Joseph E.W et al., “The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAFselective manner” PNAS, Aug. 2010, 6 Pages. [cited by applicant]
“Overview of Pharmaceutical Excipients Used in Tablets and Capsules,” Drug Topics, Oct. 2008, 11 Pages. [cited by applicant]
Torti V.R. et al., “Epithelial Tissue Hyperplasia Induced by the RAF Inhibitor PF-04880594 Is Attenuated by a Clinically Well-Tolerated Dose of the MEK Inhibitor PD-0325901” Molecular cancer therapeutics, Oct. 2012, 10 … [cited by applicant]