Targeted combined immunotherapy is expected to treat metastatic NSCLC
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Targeted combined immunotherapy is expected to treat metastatic NSCLC (non-small cell lung cancer)
Lung cancer is the second most common cancer in the world and the leading cause of cancer-related deaths worldwide. It is expected that Dato-DXd combined with “K drug” can prolong the survival period of lung cancer patients.
Recently, Dato-DXd (Datopotamab Deruxtecan), an innovative antibody-drug conjugate targeting TROP2, combined with “K drug” pembrolizumab, has achieved positive data in clinical trials for the first-line treatment of metastatic non-small cell lung cancer. !
01. If there is no response to immunotherapy, what should NSCLC patients do?
Lung cancer is the second most common cancer in the world and the leading cause of cancer-related deaths worldwide. Among them, non-small cell lung cancer (NSCLC) accounts for about 80%-85%.
More than 50% of NSCLC patients are at an advanced stage when they are diagnosed, and the prognosis is poor. Even after first-line treatment, the condition will still get worse.
In recent years, the approval of targeted therapy and immunotherapy has greatly improved the prognosis of patients with advanced NSCLC. However, some cancer patients cannot detect genomic changes that can be targeted for therapy.
Currently, the first-line standard treatment for patients with metastatic NSCLC without targeted genetic changes is PD-L1 immunotherapy, with or without platinum chemotherapy.
Although these therapies can improve the survival of this subtype of NSCLC, at least 40-60% of tumors do not respond to the initial treatment, and there will be disease progression, and new treatments are urgently needed.
02. An important target protein in solid tumors: TROP2
TROP2 (trophoblast cell surface antigen 2) is a transmembrane glycoprotein that is overexpressed in many types of solid tumors including NSCLC.
Studies have shown that in a variety of solid tumors, high expression of TROP2 is related to tumor growth and proliferation and overall disease-free survival.
Although TROP2 is expressed in all lung cancer subtypes, a study from NSCLC shows that TROP2 is expressed in all adenocarcinoma cases and 92% of squamous cell carcinoma cases (the most common form of NSCLC); and another Studies have found that TROP2 is highly expressed in 64% of adenocarcinoma and 75% of squamous cell carcinoma cases.
Currently, no therapy targeting TROP2 has been approved for the treatment of NSCLC patients.
03. Innovative drug targeting TROP2: Dato-DXd
Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) that targets TROP2 under development. It mainly consists of three parts: monoclonal antibody targeting TROP2, topoisomerase inhibitor ( DXd) and a cleavable tetrapeptidyl linker. These are linked together and can be targeted to be delivered to the inside of cancer cells to destroy cancer cells.
Moreover, compared with usual chemotherapy, the drug can also reduce the systemic exposure of cytotoxic agents. Therapies similar to this principle such as Enhertu have been approved to treat breast and stomach cancer.
Previously, in 21 evaluable triple-negative breast cancer patients, Dato-Dxd monotherapy achieved 43% overall remission rate and 95% disease control rate.
In addition to lung cancer and triple-negative breast cancer, the drug has also been tested for its efficacy and safety in other solid tumors. It can be used as a single agent or in combination with other therapies to treat HR-positive/HER2-negative breast cancer, small cell lung cancer, and urothelial cancer. Clinical trials of, gastric cancer and esophageal cancer are also underway.
04. Innovative combination therapy is worth looking forward to!
Previously, in the phase 1b TROPION-Lung02 clinical study, the safety of Dato-DXd+pembrolizumab in combination with or without platinum-containing chemotherapy was evaluated in patients with advanced or metastatic NSCLC who have previously received or have not received treatment And effectiveness.
Based on the encouraging results of the ongoing Phase 1b study, the combination therapy has entered the Phase 3 study of first-line metastatic NSCLC.
And TROPION-Lung08 is a global, open-label, randomized phase 3 trial that will evaluate the combination of Dato-DXd and pembrolizumab. Compared with pembrolizumab alone, it will be used in untreated, PD- Efficacy and safety in patients with advanced or metastatic NSCLC with high L1 expression. These patients have no known targeted genomic changes, such as EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, etc.
The primary endpoint of the trial is the assessment of progression-free survival (PFS) and overall survival (OS). TROPION-Lung08 is expected to recruit approximately 740 patients in multiple locations in Asia, Europe, North and South America.
Although PD-L1 immunotherapy can improve the prognosis of advanced or metastatic NSCLC, the progression-free survival of most patients is still less than one year. Innovative combination therapy is expected to improve this situation. It is expected that Dato-DXd combined with “K drug” can prolong the survival of patients and change the current situation of patients without targeted gene mutations and who do not respond to immunotherapy.
(source:internet, reference only)
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