IT’S TIME FOR A BISPECIFIC UPGRADE

Patients with advanced or metastatic GI cancers need innovation

Diverse GI cancers, including pancreatic, colorectal, BTC, and GEA, present a range of challenges. They're heterogeneous and complex, and most patients have advanced, metastatic disease at diagnosis.^1-3

These cancers are typically aggressive and difficult to treat. For example, patients with BTC or GEA face a dismal prognosis despite current treatment options.^1,2

Look for HER2 beyond breast cancer

Up to 26% of patients with GI cancers have HER2 overexpression.⁷

20%

of patients with BTC or GEA have HER2 alterations^7,8

 

 

 

The HER2 pathway plays a critical role in tumor growth, and current targeted options are limited^1,2,7,9

HER2 overexpression causes tumor growth by downstream signaling activation. When amplified in GI cancers, it leads to cell growth, migration, and proliferation^1,2,7,10

Current HER2-targeted approaches, including single-site binding mAbs and mAb combinations, may offer limited activity²

HER2-targeted options designed for improved inhibition are needed^2,7

 

 

 

BTC=biliary tract cancer; GEA=gastroesophageal adenocarcinoma; GI=gastrointestinal; mAb=monoclonal antibody.

Don’t let HER2 go undetected in GI cancers

Testing for HER2 is crucial to optimize therapy options for patients with advanced or metastatic
disease. Multiple modalities can be used to identify HER2^2,7,11,12:

 

 

 

Immunohistochemistry (IHC) is a common, cost-efficient modality that can be used to identify HER2 protein expression^2,11,12

 

 

 

 

 

 

Next-generation sequencing (NGS) can detect HER2 mutations and determine amplification¹¹

 

 

 

 

 

 

Other testing methods to confirm HER2 status include in situ hybridization (ISH) and fluorescence in situ hybridization (FISH)^2,7

 

 

 

The next generation of HER2 inhibition is bispecific

Dual-action bispecific antibodies can maximize HER2 inhibition.^13,14

Bispecific antibodies are designed to simultaneously bind to 2 separate receptors, or to 2 different sites on the same receptor, and to elicit antitumor activity.^15-17

Preclinical studies suggest bispecific HER2 antibodies may be able to enhance^13,14,17-19:

 

 

 

HER2 SIGNAL BLOCKADE

Breaks signal transmission to slow growth

IMMUNE-MEDIATED
CYTOTOXICITY

Recruits immune cells to kill tumor cells

HER2
INTERNALIZATION

Initiates receptor degradation

Bispecific targeting may improve HER2 inactivation.^7,14,15

 

 

 

BISPECIFIC ANTIBODIES COULD BE AN INHIBITION UPGRADE FOR PATIENTS WITH GI CANCERS^7,13,15

References: 1. Kim H, et al. Front Oncol. 2022;12:834104. 2. Zhao D, et al. J Hematol Oncol. 2019;12(1):50. 3. Sawada K, et al. Eur Onc Haematol. 2020;16(1):29-38. 4. Koshiol J, et al. BMC Cancer. 2022;22(1):1178. 5. Cancer Stat Facts: Stomach Cancer. Accessed November 2, 2023. https://seer.cancer.gov/statfacts/html/stomach.html. 6. Cancer Stat Facts: Esophageal Cancer. Accessed November 2, 2023. https://seer.cancer.gov/statfacts/html/esoph.html. 7. Oh DY, et al. Nat Rev Clin Oncol. 2020;17(1):33-48. 8. Moeini A, et al. JHEP Reports. 2021;3(2):1-13. 9. Harding JJ, et al. Lancet Oncol. 2023;24(7):772-782. 10. Yu S, et al. Exp Hematol Oncol. 2017;6:31. 11. Niu D, et al. Pathol Oncol Res. 2020;26:2577-2585. 12. Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-4625. 13. Cheng J, et al. Antibodies. 2020;9(3):49. 14. Li B, et al. Cancer Res. 2013;73(21):6471-6483. 15. Fan G, et al. J Hematol Oncol. 2015;8:130. 16. Huang S, et al. J Cancer Res Clin Oncol. 2020;146(12):3111-3122. 17. Ma J, et al. Front Oncol. 2021;12:626616. 18. Mando P, et al. Breast. 2021;60:15-25. 19. Li JY, et al. Cancer Cell. 2016;29(1):117-129.