Amgen's T-Cell Engager Tarlatamab Achieves 40% ORR in Phase II SCLC Trial; Competitor BI 764532 from Boehringer Ingelheim Advances with Fast Track Designation

Oct 24, 2023 07:20 CST Updated 07:20

Amgen

Developer of Treatment Drugs for Serious Diseases

October 24, 2023 / eMedClub News /--Today, Amgen'sBispecific T-cell engager（BiTE）Tarlatamab Shows Promising Prospects for Treating Small Cell Lung Cancer (SCLC). Tarlatamab Achieved Positive Phase II Clinical Results, with Data Presented at the 2023 European Society for Medical Oncology Congress and Published in The New England Journal of Medicine.

▲Amgen

▲Image Source:The New England Journal of Medicine

T-cell engagers for the treatment of SCLC

eMedClub

"SCLC is one of the biggest challenges in cancer treatment, with little progress made in fighting this deadly tumor over the past few decades," said David Reese, executive vice president of R&D at Amgen, in a statement.

SCLC is one of the most aggressive and devastating solid tumors.Accounting for approximately 10%-15% of lung cancer cases, thisThe median survival time after initial treatment of a disease is approximately 12 months for all stages.The 5-year relative survival rate is 7%.SCLC has a faster proliferation, higher malignancy, easier metastasis, and worse prognosis compared to non-small cell lung cancer (NSCLC).Approximately 60-70% of small cell lung cancer cases are diagnosed at the extensive stage.Most patients are prone to drug resistance and recurrence. Despite the high initial response rate to first-line platinum-based chemotherapy, patients quickly develop resistance to second-line and subsequent treatments, with a median survival time of 10 to 12 months after diagnosis. Additionally,There are currently no approved third-line treatment regimens for SCLC.。

▲ Lung Cancer Cells

Tarlatamab

eMedClub

Amgen's Tarlatamab recruits patients' T cells to tumor cells by targeting CD3 on immune cells and DLL3 on cancer cells.DLL3 is expressed on the surface of SCLC cells in approximately 85% to 94% of patients., andExpressed minimally in healthy cells, which plays a key role in Notch signaling. Once T cells are recruited and activated, they are able to attack cancer cells. Meanwhile, the therapy is also being tested in neuroendocrine prostate cancer.

Amgen stated that patients with SCLC typically have a response rate of 14% to 21% in third-line treatment for SCLC, with a median overall survival of less than six months. Clinical Phase II results for tarlatamab showed that, among 100 SCLC patients who had failed two or more prior treatments and were treated with a 10 mg dose of tarlatamab,The Objective Response Rate (ORR) reached 40%., andReach the primary endpoint of the study。The median overall survival was 14.3 months.，The median progression-free survival was only 5 months.。

Moreover, no new safety signals were observed compared to Phase 1 studies. Discontinuation due to treatment-related adverse events (TRAEs) was infrequent (4%). The most common treatment-emergent adverse events (TEAEs) reported in the 10mg dose group of tarlatamab were cytokine release syndrome (CRS; 49%), fever (38%), decreased appetite (25%), and dysgeusia (24%). Compared to previous data, the therapeutic potential of tarlatamab in patients with relapsed or refractory SCLC has been further validated.

Bispecific T-cell engagers are a new type of bispecific antibody. In addition to tarlatamab, BI 764532 from Boehringer Ingelheim also targets the DLL3/CD3 combination. Boehringer Ingelheim is a clinical-stage oncology company with therapies based on immuno-oncology and antibody-drug conjugates (ADC).Also under development is a T-cell-engaging SCLC antibody.。

Tarlatamab

eMedClub

BI 764532A treatment for SCLC and other neuroendocrine tumor patientsDLL3/CD3-IgG-like T-cell engagerUsed for the treatment of extensive-stage small cell lung cancer (ES-SCLC) and advanced or metastatic extrapulmonary neuroendocrine carcinoma (epNEC).

The discovery of BI 764532 was based on a successful collaboration initiated in 2013, leveraging Oxford BioTherapeutics' (OBT) proprietary OGAP® drug discovery platform to identify the DLL3 antigen, along with Boehringer Ingelheim's longstanding expertise in oncology and biologics development.

▲Boehringer Ingelheim

▲Oxford BioTherapeutics

BI 764532 has the same receptor target as tarlatamab.。Currently undergoing Phase I dose escalation trialAt the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO), Boehringer Ingelheim presented data from its Phase I first-in-human dose-escalation trial. These Phase I dataDemonstrated clinically acceptable safety and early efficacy in DLL3-positive ES-SCLC and epNEC patients. Just earlier this month (October 3rd),BI 764532 Granted Fast Track Designation by U.S. FDAIt is worth mentioning that the clinical trial of this candidate drug has been approved in China.

Conclusion

eMedClub

I am glad to see the research results of bispecific T-cell engagers in SCLC, a difficult-to-treat disease. Regardless of which T-cell engager is approved earlier, it will advance the treatment of SCLC, a refractory condition.

References:

1.https://www.biospace.com/article/amgen-s-t-cell-engager-shows-phase-ii-promise-in-tough-to-treat-lung-cancer-/

Statement and Copyright Notice

Disclaimer: This article aims to convey industry development information and explore the frontier progress of biopharmaceuticals. The content of the article represents the author's viewpoint and does not represent the position of EurekaMed, nor does it constitute any value judgment, investment advice, or medical guidance. If needed, please consult a professional for investment or visit a正规 hospital for medical advice.

Copyright Statement:This article is from the content team of Yi Mai Ke. Individuals are welcome to share it on their social media platforms, but unauthorized reproduction by media or organizations in any form on other platforms is prohibited. For reprint authorization, please leave a message at the bottom of the article.

Dian Dian "Share”、“Like" and "In view", charge me up a bit~"