IP Library › Granted Patent US 12,435,157
Granted Patent B2
US 12,435,157 · App. 17/530,775 · Granted Oct 7, 2025

Methods of using a bispecific antigen-binding construct targeting HER2 for the treatment of biliary tract cancers

Inventors: Diana F. Hausman (Seattle, WA); Neil C. Josephson (Seattle, WA); Rose Kamyee Lai (Seattle, WA); Gerald James Rowse (Vancouver, CA); Patrick Kaminker (Seattle, WA)
Assignee: ZYMEWORKS BC INC.
C07K16/32A61K31/7068A61K33/243A61K47/545A61K47/68031A61K47/6817A61K47/6851A61K39/00C07K2317/51C07K2317/515
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Quick Facts
Patent No.
US 12,435,157
App. No.
17/530,775
Granted
Oct 7, 2025
Kind
B2
Abstract

Described herein is a method of treating biliary tract cancer (BTC) comprising administering a bispecific antigen-binding construct targeting HER2 or a bispecific antigen-binding construct targeting HER2 linked to an auristatin analogue (ADC) to a subject.

Claims (29)

1. A method of treating a subject with HER2-positive biliary tract cancer (BTC), comprising administering an effective amount of a bispecific anti-HER2 antigen-binding construct comprising a heavy chain H1 comprising the amino acid sequence set forth in SEQ ID NO:36, a heavy chain H2 comprising the amino acid sequence set forth in SEQ ID NO:63, and a light chain L1 comprising the amino acid sequence set forth in SEQ ID NO:24 to the subject.

2. The method according to claim 1 , wherein the BTC is unresectable or metastatic.

3. The method according to claim 1 , wherein the BTC is HER2 3+, HER2 2+, or HER2 1+as measured by immunohistochemistry (IHC), wherein according to HER2 protein staining as measured by IHC:

i) HER2 1+ has an incomplete and faint/barely perceptible membrane staining in more than 10% of the tumor cells;

ii) HER2 2+ has a weak to moderate complete membrane staining in more than 10% of tumor cells; and

iii) HER2 3+ has a more than moderate complete membrane staining to strong complete membrane staining in more than 10% of tumor cells.

4. The method according to claim 3 , wherein the BTC is HER2 3+, HER2 2+, or HER2 1+as measured by immunohistochemistry (IHC), with HER2 gene amplification as measured by the levels of HER2-encoding nucleic acid in the tumor cells.

5. The method according to claim 3 , wherein the BTC is HER2 3+, HER2 2+, or HER2 1+as measured by immunohistochemistry (IHC), without HER2 gene amplification as measured by the levels of HER2-encoding nucleic acid in the tumor cells.

6. The method according to claim 1 , wherein the BTC is gall bladder cancer, ampullary carcinoma, cholangiocarcinoma (CCA), or cystic duct adenocarcinoma.

7. The method according to claim 6 , wherein the BTC is cholangiocarcinoma (CCA).

8. The method according to claim 7 , wherein the CCA is intrahepatic CCA.

9. The method according to claim 7 , wherein the CCA is extrahepatic CCA.

10. The method according to claim 1 , wherein the bispecific anti-HER2 antigen-binding construct is administered to the subject at 10 mg/kg per week.

11. The method according to claim 1 , wherein the bispecific anti-HER2 antigen-binding construct is administered to the subject at 20 mg/kg once every two weeks.

12. The method according to claim 1 , wherein the bispecific anti-HER2 antigen-binding construct is administered to the subject at 30 mg/kg once every three weeks.

13. The method according to claim 1 , wherein administering the bispecific anti-HER2 antigen-binding construct to the subject results in a complete response (CR), partial response (PR) or stable disease (SD) in the subject.

14. The method according to claim 1 , wherein the disease control rate in a group of subjects treated with the bispecific anti-HER2 antigen-binding construct is greater than 60%, 70%, or 80%.

15. The method according to claim 1 , wherein the overall response rate in a group of subjects treated with the bispecific anti-HER2 antigen-binding construct is greater than 50%, 60%, 70%, or 80%.

16. The method according to claim 1 , wherein the bispecific anti-HER2 antigen-binding construct is administered following at least one, two, or three first-line therapies.

17. The method according to claim 16 , wherein the bispecific anti-HER2 antigen-binding construct is administered following a first-line therapy comprising systemic chemotherapy, fluoropyrimidine-based chemoradiation, radiotherapy without additional chemotherapy, antibody therapy, or combinations thereof.

18. The method according to claim 17 , wherein the systemic chemotherapy comprises gemcitabine alone or in combination with a platinum-based chemotherapeutic agent.

19. The method according to claim 18 , wherein the platinum-based chemotherapeutic agent comprises cisplatin or oxaliplatin.

20. The method according to claim 17 , wherein the antibody therapy comprises an anti-PD1 antibody or an anti-PD-L1 antibody.

21. The method according to claim 1 , wherein the bispecific anti-HER2 antigen-binding construct is administered as a first-line monotherapy.

22. The method according to claim 1 , wherein the bispecific anti-HER2 antigen-binding construct is administered as an adjuvant therapy or a neoadjuvant therapy.

23. The method according to claim 1 , wherein the bispecific anti-HER2 antigen-binding construct is administered in conjunction with one or more chemotherapeutic agents.

24. The method according to claim 23 , wherein the one or more chemotherapeutic agents comprises gemcitabine, cisplatin, or combination thereof.

25. The method of claim 1 , wherein the BTC is resectable or partially resectable.

26. The method of claim 1 , wherein the BTC is metastatic or locally advanced.

Assignments (4)
CHANGE OF NAME Recorded Dec 12, 2022
From: ZYMEWORKS INC.
To: ZYMEWORKS BC INC.
Reel/Frame 062116/0071 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 2, 2021
From: HAUSMAN, DIANA F.; JOSEPHSON, NEIL C.; LAI, ROSE KAMYEE; KAMINKER, PATRICK
To: ZYMEWORKS BIOPHARMACEUTICALS INC.
Reel/Frame 058273/0135 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 2, 2021
From: ROWSE, GERALD JAMES
To: ZYMEWORKS INC.
Reel/Frame 058273/0166 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 2, 2021
From: ZYMEWORKS BIOPHARMACEUTICALS INC.
To: ZYMEWORKS INC.
Reel/Frame 058273/0199 →
Continuity (2)
Continuation PCTUS2019035042 · May 31, 2019
Related Publication 20220133903A1 · May 5, 2022
References Cited (39)
US 20150139936A1 · Frye et al. · 2015 [cited by applicant]
US 20170291955A1 · Li et al. · 2017 [cited by applicant]
US 20170355779A1 · Wickman · 2017 [cited by examiner]
JP 2017503480A · 2017 [cited by applicant]
JP 2017512765A · 2017 [cited by applicant]
WO WO2009117277A2 · 2009 [cited by applicant]
WO WO2015077891A1 · 2015 [cited by applicant]
WO WO2017185177A1 · 2017 [cited by applicant]
WO WO2019104075A1 · 2019 [cited by applicant]
WO WO2020264208A1 · 2020 [cited by applicant]
Harder J, Waiz O, Otto F, Geissler M, Olschewski M, Weinhold B, Blum HE, Schmitt-Graeff A, Opitz Og. EGFR and HER2 expression in advanced biliary tract cancer. World J Gastroenterol. Sep. 28, 2009;15(36):4511-7. doi: 10… [cited by examiner]
Galdy S, Lamarca A, McNamara MG, Hubner RA, Cella CA, Fazio N, Valle Jw. HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target? Cancer Metastasis Rev. Mar. … [cited by examiner]
Anderson et al., “Diagnosis and treatment of cholangiocarcinoma”, Oncologist. 2004;9(1):43-57. [cited by applicant]
Beeram et al., “Single Agent Activity of ZW25, a HER2-Targeted Bispecific Antibody, in HER2-Expressing Gastroesophageal and Other Cancers,” Abstract, 30th EORTC-NCI-AACR Symposium, Dublin, Ireland, 1 page. [cited by applicant]
Beeram et al., “Single Agent Activity of ZW25, a HER2-Targeted Bispecific Antibody, in HER2-Expressing Gastroesophageal and Other Cancers,” Oral Presentation, 30th EORTC-NCI-AACR Symposium, Dublin, Ireland, Nov. 14, 201… [cited by applicant]
Benavides et al., “Biliary tract cancers: SEOM clinical guidelines”, Clinical and Translational Oncology. 2015;17(12):982-7. [cited by applicant]
Benson et al., “Hepatobiliary Cancers. Version 2.2019, Featured Updated to the NCCN Guidelines”, Journal of the National Comprehensive Cancer Network, Apr. 2019, 17(4), 9 pages. [cited by applicant]
Javle et al., “HER2/neu-directed therapy for biliary tract cancer”, Journal of Hematology & Oncology, 2015, 8:58. [cited by applicant]
De Groen et al., “Biliary Tract Cancers”, The new England Journal of Medicine, Oct. 1999, pp. 1368-1378. [cited by applicant]
Javle et al., “Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study”, Lancet Oncol. Sep. 2021; 22(9):1290-300. [cited by applicant]
JP Office Action in Japanese Application No. 2021-570770, dated Aug. 2, 2023, 6 pages (with English translation). [cited by applicant]
JP Office Action in Japanese Application No. 2021-570770, dated Apr. 19, 2023, 16 pages (with English translation). [cited by applicant]
Kawamoto et al., “Overexpression and gene amplification of EGFR, HER2, and HER3 in biliary tract carcinomas, and the possibility for therapy with the HER2-targeting antibody pertuzumab”, J Gastroenterol, 2015, 50: 467-4… [cited by applicant]
Meric-Bernstam et al., “Single Agent Activity of ZW25, a HER2 Targeted Bispecific Antibody, in Heavily Pretreated HER2 Expressing Cancers,” Abstract, ASCO Annual Meeting, Chicago, IL; Jun. 1, 2018, 1 page. [cited by applicant]
Meric-Bernstam et al., “Single Agent Activity of ZW25, a HER2 Targeted Bispecific Antibody, in Heavily Pretreated HER2 Expressing Cancers,” Oral Presentation, ASCO Annual Meeting, Chicago, IL; Jun. 1, 2018, 21 pages. [cited by applicant]
Meric-Bernstam et al., “Single-Agent Activity of ZW25, a HER2 Targeted Bispecific Antibody, in HER2 Expressing Gastroesophageal and Other Cancers,” Abstract, Cholangiocarcinoma Foundation, Salt Lake City, Utah, 2 pages. [cited by applicant]
Meric-Bernstam et al., “Single-Agent Activity of ZW25, a HER2 Targeted Bispecific Antibody, in HER2 Expressing Gastroesophageal and Other Cancers,” Poster, Cholangiocarcinoma Foundation, Jan. 30-Feb. 2, 2019, Salt Lake … [cited by applicant]
Nam et al., “Therapeutic implication of HER2 in advanced biliary tract cancer”, Oncotarget. Sep. 6, 2016;7(36):58007-58021. [cited by applicant]
Sahu et al., “Targeted therapy in biliary tract cancers-current limitations and potentials in the future”, J Gastrointest Oncol. 2017;8(2):324-336. [cited by applicant]
Shengnan et al., “Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment”, Exp Hematol Oncol. Nov. 28, 2017;6:31—eCollection 2017. [cited by applicant]
Siegel et al., “Cancer statistics, 2014”, CA: A Cancer Journal for Clinicians. 2014;64(1):9-29. [cited by applicant]
Simile et al., “Targeted Therapies in Cholangiocarcinoma: Emerging Evidence from Clinical Trials”, Medicina (Kaunas). Feb. 8, 2019; 55(2):42, 16 pages. [cited by applicant]
Yamashita-Kashima et al., “Molecular targeting of HER2-overexpressing biliary tract cancer cells with trastuzumab emtansine, an antibody-cytotoxic drug conjugate”, Cancer Chemotherapy and Pharmacology, Jan. 2019, 83: 65… [cited by applicant]
Zymeworks Corporate Overview, Jun. 1, 2018, posted to https://ir.zymeworks.com/events-and-presentations, 26 pages. [cited by applicant]
Zymeworks Corporate Overview, Nov. 14, 2018, posted to https://ir.zymeworks.com/events-and-presentations, 27 pages. [cited by applicant]
Ho et al., “Biliopancreatic malignancy: future prospects for progress”, Ann Oncol., 1999, Suppl 4, p. 300-304. [cited by applicant]
Kontermann, “Recombinant bispecific antibodies for cancer therapy”, Acta Pharmacol Sin., Jan. 2005, 26(1): 1-9. [cited by applicant]
RU Office Action in Russian Application No. 2021136185, dated Oct. 20, 2023, 24 pages (with English translation). [cited by applicant]
Yu et al., “A novel asymmetrical anti-HER2/CD3 bispecific antibody exhibits potent cytotoxicity for HER2-positive tumor cells”, J Exp Clin Cancer Res., 2019, 38(1): 355, 16 pages. [cited by applicant]