Tremendous strides in science have led to a wave of precision medicine-based approaches for patients that consider each patient’s underlying genetics and what makes each patient’s cancer unique.
Tremendous strides in science have led to a wave of precision medicine-based approaches for patients that consider each patient’s underlying genetics and what makes each patient’s cancer unique. In 2020 alone, the FDA approved 19 precision medicines, accounting for 39% of new drug approvals.1
Yet, even with the availability of these precision medicines, non-targeted therapies are prescribed for the majority of cancer patients.
By focusing on difficult-to-treat cancers and relentlessly pursuing innovative modalities and targets in a variety of tumor types – including non-small cell and small cell lung cancer (NSCLC/SCLC), gastric cancer, and prostate cancer – Amgen Oncology is embracing precision medicine to quickly identify patients, tailor treatments and improve patient outcomes.
Through precision medicine-based research, Amgen scientists have been pursuing one of cancer research’s toughest challenges of the last 40 years by researching a potential targeted therapy for patients with KRAS G12C-mutated non-small cell lung cancer.
KRAS is the most prevalent driver mutation in NSCLC,2 and nearly 1/2 of all KRAS mutations in NSCLC in the U.S. are KRAS G12C.3,4 KRAS G12C occurs in roughly 13% of patients with NSCLC in the U.S.5
Despite decades of research, KRAS remained an elusive target for drug research because of the protein’s relatively smooth surface and a lack of pockets for drug binding by conventional molecules.6 Patients whose cancers harbor the KRAS mutation have limited therapeutic options and, until recently, no treatments designed to specifically target their disease.
Despite recent therapeutic advances in the treatment of gastric cancer, the fourth leading cause of cancer-related death worldwide, outcomes for patients remain poor.7 The 5-year survival rate for advanced gastric cancer continues to be among the worst of any cancer, at just 6%.8
Furthermore, until recently, it had been more than a decade since the FDA approved a new front-line treatment for advanced gastric cancer patients, and chemotherapy remains the standard of care for most HER2-negative patients across the globe.9
We recognize the need gastric cancer patients have for additional therapeutic options – and believe that the answer lies in precision medicine. One of the newest additions to Amgen’s pipeline is a potential first-in-class investigational antibody targeting the overexpression of fibroblast growth factor receptor 2b (FGFR2b) in patients with advanced gastric and gastroesophageal junction (GEJ) cancer.10 Approximately 80-85% of patients with advanced gastric and GEJ cancers are HER2-negative, and approximately 30% of these patients present with FGFR2b overexpression.11,12
Amgen’s investigational molecule, bemaritzumab, is designed to bind specifically to FGFR2b to block signaling, and enhance antibody-dependent cell-mediated toxicity. Patients with gastric/GEJ cancer whose tumors have amplification of the FGFR2 gene tend to have a worse prognosis,13-15 suggesting that inhibition of FGFR2 may be an important therapeutic strategy.16-19 FGFR2b overexpression has also been observed in several other cancers, including colorectal cancer, pancreatic cancer, breast cancer, and liver cancer.
Immuno-oncology (IO) has transformed the cancer treatment landscape. However not all patients have benefited, and we know that in certain tumor types, current IO therapies may not be effective. New and different options are needed to deliver the benefits of IO to these patients.
Amgen is working to meet this need and advance IO for patients with our innovative Bispecific T-Cell Engager or BiTE® platform, which is being investigated across a range of solid and hematological malignancies.
The BiTE platform is a targeted IO platform engineered to engage a patient’s own T cells against cancer. BiTE therapies are bispecific, meaning they are engineered from two antibodies – one of which is designed to engage with CD3 on T cells, and the other with a selected tumor antigen.20
This versatile technology has been studied in thousands of patients21 and is currently being investigated in a variety of cancers with tumor-associated antigens – including DLL3 in small-cell lung cancer and neuroendocrine prostate cancer, PSMA in prostate cancer, MUC17 and CLDN18.2 in gastric cancer, and BCMA in multiple myeloma.22 The BiTE platform is designed to not depend on the ex-vivo manipulation of a patient’s T cells, with the goal of being readily available to patients regardless of treatment setting.
Targeted approaches in oncology represent a hopeful leap forward in certain treatment paradigms by allowing patients to be treated based on their individual tumor rather than with non-specific therapies. However, the benefits of some of these targeted treatments can’t be realized without biomarker testing to understand each patient’s unique genetic makeup and assess whether targeted therapy is appropriate.
For that reason, Amgen is committed to driving broad accessibility to biomarker testing, thus ensuring that patients and physicians have access to high quality diagnostics to inform treatment options during the course of their disease.
For over 40 years, a core part of Amgen’s mission has been to identify areas of unmet medical need for cancer patients and bring innovative treatment options to those patients – such as precision medicine – as quickly as possible. At Amgen, we believe we are on the cusp of the next generation of targeted cancer treatments, and our hope is that this work will accelerate the use of precision medicine to benefit all cancer patients.
1. Personalized Medicine Coalition. Personalized Medicine at FDA. Available at: http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/PM_at_FDA_The_Scope_Significance_of_Progress_in_2020.pdf?_zs=02X7b&_zl=ihuQ2. Accessed 5/5/21.
2. Pakkala S, et al. JCI Insight. 2018:e120858.
3. Arbour KC, et al. Clin Cancer Res. 2018;24:334-340.
4. Cox AD, et al. Nat Rev Drug Discov. 2014;13:828-851.
5. Amgen Data on File: Analysis of AACR Genie v8, 7-A-Table.
6. Ryan MB, et al. Nat Rev Clin Oncol. 2018;15:709-720.
7. World Health Organization. Globocan 2020: Stomach. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf. Accessed 5/5/2021
8. American Cancer Society. Stomach Cancer Survival Rates. Available at: https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html. Accessed 5/5/2021.
9. United States Food and Drug Administration. FDA Approves First Immunotherapy for Initial Treatment of Gastric Cancer. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-initial-treatment-gastric-cancer. Accessed 5/5/2021.
10. Catenacci DV, et al. Future Oncol. 2019;15:2073-2082.
11. Shitara K et al. N Engl J Med. 2020; 382;25:2419-2430.
12. Wainberg ZA, et al. Presented at: ASCO Gastrointestinal Cancer Symposium; January 15-16, 2021; Online Virtual Scientific Program (Abstract LBA160 and oral presentation).
13. Su X , et al. Br J Cancer. 2014;110: 967–975.
14. Seo S, et al. Oncotarget. 2017;8:33844–33854.
15. Ahn S, et al. Mod Pathol. 2016;29:1095-1103.
16. Jung EJ, et al. Hum Pathol. 2012;43:1559-1566.
17. Matsumoto K, et al. Br J Cancer. 2012;106:727-732.
18. Zhao WM, et al. Clin Cancer Res. 2010;16:5750-5758.
19. Xie L, et al. Clin Cancer Res. 2013;19:2572-2583.
20. Baeuerle PA, et al. Curr Opin Mol Ther. 2009;11:22-30.
21. Amgen Data on File, 2019.
22. Amgen Pipeline. Available at : https://www.amgenpipeline.com/-/media/themes/amgen/amgenpipeline-com/amgenpipeline-com/pdf/amgen-pipeline-chart.pdf. Accessed May 10, 2021.