Recently, Daiichi Sankyo and AstraZeneca announced a clinical trial collaboration to determine whether using a combination of TAGRISSO (osimertinib) and patritumab deruxtecan (U3-1402) would be effective in treating patients with EGFR-mutated non-small cell lung cancer (NSCLC).
NSCLC
According to the American Cancer Society, non-small cell lung cancer (NSCLC) is one of two main forms of lung cancer. They note:
About 80% to 85% of lung cancers are NSCLC. The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.
Adenocarcinomas begin in mucus-secreting or substance-secreting cells. Generally, this form of NSCLC affects current or former smokers. It occurs more in females than males, and often occurs in younger individuals. Next, squamous cell carcinomas begin in squamous cells, which line your airways. Again, this type of cancer is often linked to smoking. Finally, large cell carcinoma appears in any part of the lung. It often grows and metastasizes rapidly. There are also rarer forms of NSCLC, such as sarcomatoid carcinoma.
In patients with EGFR-mutated NSCLC, their bodies usually over-express epidermal growth factor receptor (EGFR). Up to 30% of patients with NSCLC have an EGFR mutation. An article in the Journal of Thoracic Disease notes that:
EGFR expression in NSCLC is associated with reduced survival, frequent lymph node metastasis, and poor chemosensitivity.
Symptoms include, but are not limited to:
- Fatigue
- Coughing up phlegm, blood, or mucus
- Chest pain
- Loss of appetite
- Unintended weight loss
- Shortness of breath
Learn more about NSCLC here.
HER3 Therapies
According to Dr. Gilles Gallant, BPharm, PhD:
“The majority of patients with EGFR-mutated NSCLC overexpress the HER3 protein in cancer cells.”
While current treatments like TAGRISSO, an EGFR tyrosine kinase inhibitor (TKI), are generally helpful in treating lung cancer, there is a potential problem. HER3 protein is able to resist TKIs, making them relatively ineffective in the case of patients with EGFR mutations. Unfortunately, there are no approved HER3 therapies.
However, that may change with patritumab deruxtecan (U3-1402), an investigational HER3 directed DXd antibody drug conjugate (ADC) developed by Daiichi Sankyo. Antibody drug conjugates deliver chemotherapy straight to cancer cells via a monoclonal antibody. This allows the therapy to bind to a specific target, making it a customized and targeted treatment option. In this case, U3-1402 is made of an anti-HER3 antibody which will target any cancer cells that express the protein.
In the collaboration with Daiichi Sankyo and Astrazeneca, the pair will hold a Phase 1 trial to determine whether a patritumab deruxtecan-TAGRISSO combination is safe and effective as a first- or second-line therapy.
During Phase 1, researchers will determine the safety, efficacy, and tolerability of different doses. This will help researchers establish a recommended dose for patients. Next, in Phase 2, researchers will examine the efficacy of U3-1402 alone or with TAGRISSO. The international study hopes to enroll 258 patients.
