IP Library › Granted Patent US 12,528,869
Granted Patent B2
US 12,528,869 · App. 17/411,158 · Granted Jan 20, 2026

Treatment of non-small cell lung cancer with EGFR mutations

Inventors: Roland Knoblauch (Doylestown, PA); Sheri Moores (Wayne, PA)
Assignee: Janssen Biotech, Inc.
C07K16/2863A61K45/06A61P35/00A61K2039/505
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Quick Facts
Patent No.
US 12,528,869
App. No.
17/411,158
Granted
Jan 20, 2026
Kind
B2
Abstract

The present invention relates to treatment of subjects having EGFR exon 20 insertion and other uncommon EGFR mutations.

Claims (49)

1 . A method of treating a subject having cancer that is positive for an EGFR exon 20 mutation, the method comprising:

administering a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody to the subject, the administering comprising a first 28-day cycle wherein about 1050 mg or about 1400 mg of the bispecific antibody is administered weekly for 4 weeks, followed by one or more 28-day cycles wherein about 1050 mg or about 1400 mg of the bispecific antibody is administered biweekly, the one or more 28-day cycles beginning after the first 28-day cycle to thereby treat the cancer,

wherein the cancer has progressed on or after platinum-based chemotherapy and is a locally advanced or metastatic non-small cell lung cancer (NSCLC), and wherein the bispecific anti-EGFR/c-Met antibody comprises:

a first domain that specifically binds EGFR and comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and

a second domain that specifically binds c-Met and comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 7, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 8, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 9, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12.

2 . The method of claim 1 , comprising, prior to the administering, determining a presence or an absence of the EGFR exon 20 mutation in a sample from the subject.

3 . The method of claim 1 , wherein the first domain comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 13 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, and the second domain comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16.

4 . The method of claim 1 , wherein the bispecific anti-EGFR/c-Met antibody is an IgG1 isotype.

5 . The method of claim 3 , wherein the bispecific anti-EGFR/c-Met antibody comprises a first heavy chain (HCl) comprising the amino acid sequence of SEQ ID NO: 17, a first light chain (LC1) comprising the amino acid sequence of SEQ ID NO: 18, a second heavy chain (HC2) comprising the amino acid sequence of SEQ ID NO: 19, and a second light chain (LC2) comprising the amino acid sequence of SEQ ID NO: 20.

6 . The method of claim 1 , wherein the bispecific anti-EGFR/c-Met antibody comprises a biantennary glycan structure with a fucose content of about 1% to about 15%.

7 . The method of claim 1 , comprising further administering one or more anti-cancer therapies to the subject.

8 . The method of claim 7 , wherein the one or more anti-cancer therapies comprise chemotherapy, radiation therapy, surgery, a targeted anti-cancer therapy, a kinase inhibitor, or any combination thereof.

9 . The method of claim 8 , wherein the kinase inhibitor is an inhibitor of EGFR, an inhibitor of c-Met, an inhibitor of HER2, an inhibitor of HER3, an inhibitor of HER4, an inhibitor of VEGFR, or an inhibitor of AXL.

10 . The method of claim 9 , wherein the kinase inhibitor is lazertinib, poziotinib, erlotinib, gefitinib, lapatinib, vandetanib, afatinib, osimertinib, criotinib, cabozantinib, capmatinib, axitinib, lenvatinib, nintedanib, regorafenib, pazopanib, sorafenibi, or sunitinib.

11 . The method of claim 1 , wherein the EGFR exon 20 mutation is a de novo mutation.

12 . The method of claim 1 , wherein the EGFR exon 20 insertion mutation is selected from: an insertion of Ala (A) between M766 and A767, an insertion of Ser, Val and Ala (SVA) between S768 and V769, an insertion of Asn and Ser (NS) between P772 and H773, an insertion of one or more amino acids between D761 and E762, A763 and Y764, Y764 and Y765, M766 and A767, A767 and V768, S768 and V769, V769 and D770, D770 and N771, N771 and P772, P772 and H773, H773 and V774, V774 and C775, or any combination thereof an acquired mutation.

13 . The method of claim 1 , wherein the administering provides an improvement in overall response rate, partial response rate, or a combination thereof.

14 . A method of treating a subject having locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for an EGFR exon 20 insertion mutation, the method comprising:

administering a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody to the subject, the administering comprising a first 28-day cycle wherein about 1050 mg of the bispecific antibody is administered weekly for 4 weeks, followed by one or more 28-day cycles, wherein about 1050 mg of the bispecific antibody is administered biweekly, the one or more 28-day cycles begining after the first 28-day cycle to thereby treat the NSCLC,

wherein the subject weighs less than 80 kg and the NSCLC has progressed on or after platinum-based chemotherapy, and

the bispecific anti-EGFR/c-Met antibody comprises:

a first domain that specifically binds EGFR and comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and

a second domain that specifically binds c-Met and comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 7, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 8, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 9, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12.

15 . A method of treating a subject having locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for an EGFR exon 20 insertion mutation, the method comprising:

administering a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody to the subject, the administering comprising a first 28-day cycle wherein about 1400 mg of the bispecific antibody is administered weekly for 4 weeks, followed by one or more 28-day cycles wherein about 1400 mg of the bispecific antibody is administered biweekly, the one or more 28-day cycles begining after the first 28-day cycle to thereby treat the NSCLC,

wherein the subject weighs greater than or equal to 80 kg and the NSCLC has progressed on or after platinum-based chemotherapy, and

the bispecific anti-EGFR/c-Met antibody comprises:

a first domain that specifically binds EGFR and comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and

a second domain that specifically binds c-Met and comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 7, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 8, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 9, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12.

16 . A method of treating a subject having locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for an EGFR exon 20 insertion mutation, the method comprising:

administering a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody to the subject, the administering comprising a first 28-day cycle wherein about 1050 mg of the bispecific antibody is administered weekly for 4 weeks, followed by one or more 28-day cycles wherein about 1050 mg of the bispecific antibody is administered biweekly, the one or more 28-day cycles beginning after the first 28-day cycle to thereby treat the NSCLC,

wherein the subject weighs less than 80 kg and the NSCLC has progressed on or after platinum-based chemotherapy, and

wherein the bispecific anti-EGFR/c-Met antibody comprises:

a first domain that specifically binds EGFR and comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 13 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, and

a second domain that specifically binds c-Met and comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16.

17 . A method of treating a subject having locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for an EGFR exon 20 insertion mutation, the method comprising:

administering a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody to the subject, the administering comprising a first 28-day cycle wherein about 1050 mg of the bispecific antibody is administered weekly for 4 weeks, followed by one or more 28-day cycles wherein about 1050 mg of the bispecific antibody is administered biweekly, the one or more 28-day cycles beginning after the first 28-day cycle to thereby treat the NSCLC,

wherein the subject weighs less than 80 kg and the NSCLC has progressed on or after platinum-based chemotherapy, and

wherein the bispecific anti-EGFR/c-Met antibody comprises a first heavy chain (HC1) comprising the amino acid sequence of SEQ ID NO: 17, a first light chain (LC1) comprising the amino acid sequence of SEQ ID NO: 18, a second heavy chain (HC2) comprising the amino acid sequence of SEQ ID NO: 19, and a second light chain (LC2) comprising the amino acid sequence of SEQ ID NO: 20.

18 . A method of treating a subject having locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for an EGFR exon 20 insertion mutation, the method comprising:

administering a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody to the subject, the administering comprising a first 28-day cycle wherein about 1400 mg of the bispecific antibody is administered weekly for 4 weeks, followed by one or more 28-day cycles wherein about 1400 mg of the bispecific antibody is administered biweekly, the one or more 28-day cycles beginning after the first 28-day cycle to thereby treat the NSCLC,

wherein the subject weighs greater than or equal to 80 kg and the NSCLC has progressed on or after platinum-based chemotherapy, and

wherein the bispecific anti-EGFR/c-Met antibody comprises:

a first domain that specifically binds EGFR and comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 13 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 14, and

a second domain that specifically binds c-Met and comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16.

19 . A method of treating a subject having locally advanced or metastatic non-small cell lung cancer (NSCLC) that is positive for an EGFR exon 20 insertion mutation, the method comprising:

administering a therapeutically effective amount of an isolated bispecific anti-epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody to the subject, the administering comprising a first 28-day cycle wherein about 1400 mg of the bispecific antibody is administered weekly for 4 weeks, followed by one or more 28-day cycles wherein about 1400 mg of the bispecific antibody is administered biweekly, the one or more 28-day cycles beginning after the first 28-day cycle to thereby treat the NSCLC,

wherein the subject weighs greater than or equal to 80 kg and the NSCLC has progressed on or after platinum-based chemotherapy, and

wherein the bispecific anti-EGFR/c-Met antibody comprises a first heavy chain (HC1) comprising the amino acid sequence of SEQ ID NO: 17, a first light chain (LC1) comprising the amino acid sequence of SEQ ID NO: 18, a second heavy chain (HC2) comprising the amino acid sequence of SEQ ID NO: 19, and a second light chain (LC2) comprising the amino acid sequence of SEQ ID NO: 20.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2023
From: MOORES, SHERI
To: CENTOCOR RESEARCH & DEVELOPMENT, INC.
Reel/Frame 062987/0797 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2023
From: KNOBLAUCH, ROLAND
To: JANSSEN RESEARCH & DEVELOPMENT, LLC
Reel/Frame 062987/0863 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2023
From: CENTOCOR RESEARCH & DEVELOPMENT, INC.
To: JANSSEN BIOTECH, INC.
Reel/Frame 062987/0941 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2023
From: JANSSEN RESEARCH & DEVELOPMENT, LLC
To: JANSSEN BIOTECH, INC.
Reel/Frame 062988/0046 →
Continuity (2)
Provisional Application 63069748 · Aug 25, 2020
Related Publication 20220064306A1 · Mar 3, 2022
References Cited (125)
US 5837242A · Holliger et al. · 1998 [cited by applicant]
US 8242247B2 · Klein et al. · 2012 [cited by applicant]
US 9242247B2 · Lafond et al. · 2016 [cited by applicant]
US 9593164B2 · Chiu et al. · 2017 [cited by applicant]
US 11459391B2 · Moores et al. · 2022 [cited by applicant]
US 20020018749A1 · Hudson et al. · 2002 [cited by applicant]
US 20050272083A1 · Seshagiri · 2005 [cited by applicant]
US 20070148774A1 · McCafferty et al. · 2007 [cited by applicant]
US 20070287170A1 · Davis et al. · 2007 [cited by applicant]
US 20090182127A1 · Naergaard et al. · 2009 [cited by applicant]
US 20100015133A1 · Igawa et al. · 2010 [cited by applicant]
US 20100028637A1 · Tavsanli et al. · 2010 [cited by applicant]
US 20110123532A1 · Gurney et al. · 2011 [cited by applicant]
US 20120149876A1 · Von et al. · 2012 [cited by applicant]
US 20130195849A1 · Spreter et al. · 2013 [cited by applicant]
US 20130216548A1 · Neijssen et al. · 2013 [cited by applicant]
US 20140141000A1 · Chiu · 2014 [cited by examiner]
US 20170362325A1 · Jung et al. · 2017 [cited by applicant]
US 20190153115A1 · Schellenberger et al. · 2019 [cited by applicant]
US 20200087407A1 · Chiu et al. · 2020 [cited by applicant]
US 20210017285A1 · Laquerre et al. · 2021 [cited by applicant]
US 20220298248A1 · Henley et al. · 2022 [cited by applicant]
EP 0281604B1 · 1993 [cited by applicant]
WO 8801649A1 · 1988 [cited by applicant]
WO 9201047A1 · 1992 [cited by applicant]
WO 9413804A1 · 1994 [cited by applicant]
WO 9844001A1 · 1998 [cited by applicant]
WO 2006028936A2 · 2006 [cited by applicant]
WO 2009018386A1 · 2009 [cited by applicant]
WO 2009080251A1 · 2009 [cited by applicant]
WO 2009080252A1 · 2009 [cited by applicant]
WO 2009080254A1 · 2009 [cited by applicant]
WO 2011131746A2 · 2011 [cited by applicant]
WO 2018094225A1 · 2018 [cited by applicant]
WO 2020102647A1 · 2020 [cited by applicant]
Cho et al (JNJ-61186372 (JNJ-372), an EGFR-cMET bispecific antibody, in advanced non-small cell lung cancer (NSCLC): An update on phase I results, Abstracts | NSCLC, metastatic| vol. 29, supplement 8, viii542, Oct. 2018… [cited by examiner]
Murphy et al (“Erlotinib or gefitinib for the treatment of relapsed platinum pretreated non-small cell lung cancer and ovarian cancer: a systematic review.” Drug resistance updates : reviews and commentaries in antimicr… [cited by examiner]
Goździk-Spychalska et al. (“C-MET inhibitors in the treatment of lung cancer.” Current treatment options in oncology vol. 15,4 (2014): 670-82. doi:10.1007/s11864-014-0313-5). (Year: 2014). [cited by examiner]
NCT02609776 (Year: 2019). [cited by examiner]
Ahn, et al., “Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: results from the dose escalation and dose expansion parts of a first-in-human, openlabel, multicentre, phase 1-2 stud… [cited by applicant]
Cappuzzo et al., “Epidermal Growth Factor Receptor Gene and Protein and Gefi tinib Sensitivity in Non-Small-Cell Lung Cancer”, J. Natl. Cancer Inst., 2005, 97, 643-655. [cited by applicant]
Chothia et al., “Canonical Structures for the Hypervariable Regions of Immunoglobulins”, J. Mol. Biol., 1987, 196, 901-917. [cited by applicant]
ClinicalTrails.gov, “Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (Chrysalis)”, NCT02609776, Aug. 14, 2020 pp. 1-13. [cited by applicant]
Ferrara et al., “Modulation of Therapeutic Antibody Effector Functions by Glycosylation Engineering: Influence of Golgi Enzyme Localization Domain and Co-Expression of Heterologous b1, 4-N-acetylglucosaminyltransferase … [cited by applicant]
Ferrara et al., “The Carbohydrate at FcRIIIa Asn-162 an Element Required for High Affinity Binding to non-fucosylated IgG Glycoforms”, J. Biol. Chem, 2006, 281, 5032-5036. [cited by applicant]
Gazdar, “Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors”, Oncogene, 2009, 28 Suppl. , S24-S31. [cited by applicant]
Haura, et al., “JNJ-61186372 (JNJ-372), an EGFR-cMet bispecific antibody, in EGFR-driven advanced non-small cell lung cancer (NSCLC)”, Journal of Clinical Oncology, vol. 37, No. 15, 2019, Supplement, p. 9009. [cited by applicant]
Honegger et al., “Yet Another Numbering Scheme for Immunoglobulin Variable Domains: An Automatic Modeling and Analysis Tool”, J. Mol. Biol., 2001, 309, 657-670. [cited by applicant]
Hong et al., “P3.02b-119 YH25448, a highly selective 3rd generation EGFR TKI, exhibits superior survival over osimertinib in animal model with brain meta-stases from NSCLC: topic: EGFR RES”, J. Thorac. Oncol., 2017, vol… [cited by applicant]
Hynes et al., “ERBB receptors and cancer: The Complexity of Targeted Inhibitors”, Nature Reviews Cancer, 2005, 5, 341-354. [cited by applicant]
Janne et al., “Antitumor activity of TAK-788 in NSCLC with EGFR exon 20 insertions”, J. Clin. Oncol., 2019, 37(15), 1 page. [cited by applicant]
Janne et al.,, “Effect of Epidermal Growth Factor Receptor Tyrosine Kinase Domain Mutations on the Outcome of Patients with Non-Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibi… [cited by applicant]
Kabat et al., “Sequences of proteins of immunological interest, 5th Ed., Public Health Service”, National Institutes of Health, Bethesda, MD, 1991. [cited by applicant]
Konno et al., “Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity”, Cytotechnology, 2012, 64, 249-265. [cited by applicant]
Kris et al., “Using Multiplexed Assays of oncogenic drivers in lung cancers to select targeted drugs”, Jama-J Am Med Assoc., 2014, 311(19), 1998-2006. [cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains”, Dev. Comp. Immunol., 2003, 27, 55-77. [cited by applicant]
Li, et al., “Efficacy and long-term survival of advanced lung adenocarcinoma patients with uncommon EGFR mutations treated with 1st generation EGFR-TKIs compared with chemotherapy as first-line therapy”, Lung cancer (Am… [cited by applicant]
Li, et al., “Four generations of EGFR TKIs associated withdifferent pathogenic mutations in non-small cell lung carcinoma”, J. Drug. Target. Epub., vol. 28, No. 9, Mar. 12, 2020, p. 861-872. [cited by applicant]
Martin et al., “Structural Families in Loops of Homologous Proteins: Automatic Classification, Modeling and Application to Antibodies”, J. Bmol. Biol., 1996, 263, 800-815. [cited by applicant]
Mori et al., “Engineering Chinese Hamster Ovary Cells to Maximize Effector Function of Produced Antibodies Using FUT8 siRNA”, Biotechnol Bioeng., 2004, 88, 901-908. [cited by applicant]
Nakata et al., “Recent understanding of the molecular mechanisms for the efficacy and resistance of EGF receptor-specific tyrosine kinase inhibitors in non-small cell lung cancer”, Expert Opinion on Therapeutic Targets,… [cited by applicant]
Olivier et al., “EB66 cell line, a duck embryonic stem cellderived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity”, MAbs, 2010, 2(4), 405-415. [cited by applicant]
Oxnard et al., “Natural history and molecular characteristics of lung cancers harboring EGFR Exon 20 Insertions”, Journal of thoracic oncology, 2013, 8(2), 179-184. [cited by applicant]
Riess et al., “Diverse EGFR Exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC”, Journal of Thoracic Oncology, 2018, 13(10), 1560-1568. [cited by applicant]
Russo et al., “Heterogeneous responses to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with uncommon EGFR mutations, New insights and future perspectives in this complex clinical… [cited by applicant]
Shields et al., “Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcyRIII and Antibody-dependent Cellular Toxicity*”, J. Biol. Chem., 2002, 277, 26733-26740. [cited by applicant]
Shinkawa et al., “The Absence of Fucose but Not the Presence of Galactose or Bisecting N-Acetylglucosamine of Human IgG1 Complex-type Oligosaccharides Shows the Critical Role of Enhancing Antibody-dependent Cellular Cyt… [cited by applicant]
Sousa, et al., “Detection of rare and novel EGFR mutations in NSCLC patients: Implications for treatment-decision”, Lung Cancer, Jan. 2020, vol. 139, 35-40. [cited by applicant]
Travis, “2015 WHO classification of the Pathology and Genetics of Tumors of the Lung”, Journal of Thoracic Oncology, 2015, 10(9), S68-S. [cited by applicant]
Tsigelny et al., “Molecular determinants of drug-specific sensitivity for epidermal growth factor receptor (EGFR) exon 19 and 20 mutants in non-small cell lung cancer”, Oncotarget, 2015, 6(8), 6029-6039. [cited by applicant]
Turke et al., “Preexistence and Clonal Selection of MET Amplification in EGFR Mutant NSCLC”, Cancer Cell, 2010, 17, 77-88. [cited by applicant]
Ullrich et al., “Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells”, Nature, 1984, 309, 418-425. [cited by applicant]
Vyse et al., “Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer”, Signal transduction and targeted therapy, 2019, 4:5, 10 pages. [cited by applicant]
Wu et al., “An analysis of the sequences of the variable regions of Bence Jones Proteins and myeloma light chains and their implications for anti-body complementarity”, J. Exp.. Med., 1970, 132, 211-250. [cited by applicant]
Yang et al., “A phase 2 study of poziotinib in patients with EGFR or HER2 exon 20 mutation-positive non-small cell lung cancer”, J. Clin. Oncol., 2018, 36(15). [cited by applicant]
Yasuda et al., “Structural biochemical and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer”, Science translational medicine, 2013, 5(216), 216ral77. [cited by applicant]
Zang et al., “Treatment of uncommon EGFR mutations in non-small cell lung cancer: new evidence and treatment”, Transl. Lung Cancer Res., Jun. 2019, 8(3), 302-316. [cited by applicant]
Zhong et al., “The resistance mechanisms and treatment strategies for EGFR-mutant advanced non-small-cell lung cancer”, Oncotarget, 2017, 8(41), 71358-71370. [cited by applicant]
Zhou et al., “Development of a Simple and Rapid Method for Producing Non-Fucosylated Oligomannose Containing Antibodies With Increased Effector Function”, Biotechnol Bioeng., 2008, 99, 652-665. [cited by applicant]
Baraibar et al., “Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC”, Critical Reviews in Oncology/Hematology, vol. 148, Feb. 7, 2020, 102906, pp. 1-13. [cited by applicant]
Moores et al., “A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors”, Cancer Research, Jul. 1, 2016, vol. 76, No. 13, pp. 3942-3953. [cited by applicant]
Wu et al., “Effectiveness of tyrosine kinase inhibitors on “uncommon” epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer”, Clin Cancer Reserach, Jun. 1, 2011, vol. … [cited by applicant]
Yun et al., “Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC”, Cancer Discovery, May 15, 2020, vol. 10, No. 8, 1194-1209. [cited by applicant]
Aggarwal et al., “Influence of TP53 mutation on survival in patients with advanced EGFR-mutant non-small-cell lung cancer”, JCO Precision Oncology, 2018, vol. 2, pp. 1-28. [cited by applicant]
Alam et al., “DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53”, Cell Death & Differentiation, 2016, vol. 23, No. 4, pp. 707-722. [cited by applicant]
Anonymous, “Poziotinib shows promise for rare lung cancer”, Cancer Discovery, 2018, vol. 8, pp. 1-6. [cited by applicant]
Anonymous, “Spectrum's Poziotinib Failed to Meet Primary Phase II Trial Endpoint” Precision Oncology News Dec. 27, 2019, 2pp. [cited by applicant]
Calabresi et al., “Basic Principles And Clinical Management Of Cancer”, Medical oncology, 1985, Chapter 10, 1352 pages. [cited by applicant]
Canale et al., “Impact of TP53 mutations on outcome in EGFR-mutated patients treated with first-line tyrosine kinase inhibitors”, Clinical Cancer Research, 2017, vol. 23, No. 9, pp. 2195-2202. [cited by applicant]
Cha et al., “Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models”, International Journal of Cancer, 2012, vol. 130, No. 10, pp. 2445-… [cited by applicant]
Commins et al., “Immunologic messenger molecules: cytokines, interferons, and chemokines”, Immunology, 2010, vol. 125, No. 2, pp. S53-S72. [cited by applicant]
Conde et al., “Molecular context of the EGFR mutations: evidence for the activation of mTOR/S6K signaling”, Clinical Cancer Research, 2006, vol. 12, No. 3, pp. 710-717. [cited by applicant]
Costa et al., “BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations”, PLOS Medicine, 2007, vol. 4, No. 10, pp. 1669-1680. [cited by applicant]
Cragg et al., “Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics”, PLOS Medicine, 2007, vol. 4, No. 10, pp. 1681-1690. [cited by applicant]
Fang et al., “EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer”, BMC Cancer, 2019, vol. 19, Article 595, pp. 1-9. [cited by applicant]
Fauriat et al., “Regulation of human NK-cell cytokine and chemokine production by target cell recognition”, Blood, 2010, vol. 115, No. 11, pp. 2167-2176. [cited by applicant]
Frega et al., “Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations”, Oncotarget, 2017, vol. 8, No. 20, p. 326… [cited by applicant]
Grugan et al., “Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells”, mAbs, 2017, vol. 9, No. 1, pp. 114-126. [cited by applicant]
Heymach et al., “A phase II trial of poziotinib in EGFR and HER2 exon 20 mutant non-small cell lung cancer (NSCLC)”, Journal of Thoracic Oncology, 2018, vol. 13, No. 10, pp. S323-S324. [cited by applicant]
Jarantow et al., “Impact of cell-surface antigen expression on target engagement and function of an epidermal growth factor receptor x c-MET bispecific antibody”, Journal of Biological Chemistry, 2015, vol. 290, No. 41,… [cited by applicant]
Kosaka et al., “Response heterogeneity of EGFR and HER2 exon 20 insertions to covalent EGFR and HER2 inhibitors”, Cancer Research, 2017, vol. 77, No. 10, pp. 2712-2721. [cited by applicant]
Lin et al., “R280T mutation of p53 gene promotes proliferation of human glioma cells through GSK3ß/PTEN pathway”, Neuroscience Letters, 2012, vol. 529, No. 1, pp. 60-65. [cited by applicant]
Mantovani et al., “Mutant p53 as a guardian of the cancer cell”, Cell Death & Differentiation, 2019, vol. 26, No. 2, pp. 199-212. [cited by applicant]
Melnikova et al., “Mutant p53 is constitutively phosphorylated at serine 15 in UV-induced mouse skin tumors: involvement of ERK1/2 Map kinase”, Oncogene, 2003, vol. 22, No. 38, pp. 5958-5966. [cited by applicant]
Nagano et al., “Mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors and a potential treatment strategy”, Cells, 2018, vol. 7, No. 11, Article 212, pp. 1-16. [cited by applicant]
National Center for Biotechnology Information, “Epidermal growth factor receptor isoform a precursor [Homo sapiens]”, GenBank Accession No. NP_005219.2, 2022, pp. 1-7. [cited by applicant]
National Center for Biotechnology Information, “Hepatocyte growth factor receptor isoform a preproprotein [Homo sapiens]”, GenBank Accession No. NP_001120972.1, 2022, pp. 1-4. [cited by applicant]
Okada et al., “Application of highly immunocompromised mice for the establishment of patient-derived xenograft (PDX) models”, Cells, 2019, vol. 8, No. 8, Article 889, pp. 1-18. [cited by applicant]
Okada et al., “EGFR downregulation after anti-EGFR therapy predicts the antitumor effect in colorectal cancer”, Molecular Cancer Research, 2017, vol. 15, No. 10, pp. 1445-1454. [cited by applicant]
Puchalapalli et al., “NSG mice provide a better spontaneous model of breast cancer metastasis than athymic (nude) mice”, PLOS One, 2016, vol. 11, No. 9, Article e0163521, pp. 1-15. [cited by applicant]
Ramalingam et al., “Dual inhibition of the epidermal growth factor receptor with cetuximab, an IgG1 monoclonal antibody, and gefitinib, a tyrosine kinase inhibitor, in patients with refractory non-small cell lung cancer… [cited by applicant]
Reefman et al., “Cytokine secretion is distinct from secretion of cytotoxic granules in NK cells”, The Journal of Immunology, 2010, vol. 184, No. 9, pp. 4852-4862. [cited by applicant]
Robichaux et al., “Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer”, Nature Medicine, 2018, vol. 24, No. 5, pp. 638-646. [cited by applicant]
Roerink et al., “Intra-tumour diversification in colorectal cancer at the single-cell level”, Nature, 2018, vol. 556, No. 7702, pp. 457-462. [cited by applicant]
Sachs et al., “Long-term expanding human airway organoids for disease modeling”, The EMBO Journal, 2019, vol. 38, No. 4, p. e100300. [cited by applicant]
Satoh et al., “Non-fucosylated therapeutic antibodies as next-generation therapeutic antibodies”, Expert Opinion on Biological Therapy, 2006, vol. 6, No. 11, pp. 1161-1173. [cited by applicant]
Sauer et al., “Mutant p53 initiates a feedback loop that involves Egr-1/EGF receptor/ERK in prostate cancer cells”, Oncogene, 2010, vol. 29, No. 18, pp. 2628-2637. [cited by applicant]
Sellmann et al., “Balancing selectivity and efficacy of bispecific epidermal growth factor receptor (EGFR) x c-MET antibodies and antibody-drug conjugates”, Journal of Biological Chemistry, 2016, vol. 291, No. 48, p. 25… [cited by applicant]
Shi et al., “Overcoming acquired resistance to AZD9291, a third-generation EGFR inhibitor, through modulation of MEK/ERK-dependent Bim and Mcl-1 degradation”, Clinical Cancer Research, 2017, vol. 23, No. 21, pp. 6567-65… [cited by applicant]
Sunada et al., “Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation”, Proceedings of the National Academy of Sciences of the United States of America… [cited by applicant]
Troy, “Remington: the science and practice of pharmacy”, Lippincott Williams & Wilkins, 2006, 21st Edition, pp. 691-1092. [cited by applicant]
Wang et al., “Natural killer cell-produced IFN -? and TNF-a induce target cell cytolysis through upregulation of ICAM-1”, Journal of Leukocyte Biology, 2012, vol. 91, No. 2, pp. 299-309. [cited by applicant]
Wang et al., “NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy”, Frontiers in Immunology, 2015, vol. 6, pp. 1-15. [cited by applicant]
Wong et al., “Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer”, Clinical Therapeutics, 2005, vol. 27, No. 6, pp. 684-694. [cited by applicant]
Zhu et al., “Silencing of mutant p53 by siRNA induces cell cycle arrest and apoptosis in human bladder cancer cells”, World Journal of Surgical Oncology, 2013, vol. 11, Article 22, pp. 1-11. [cited by applicant]