Week 2, September 2024: Non-Small Cell Lung Cancer

News from the IASLC 2024 World Conference on Lung Cancer (WCLC24) has provided several updates on the clinical trial space for non-small cell lung cancer (NSCLC), with several antibody-based drugs at the forefront. NSCLC is the most common type of lung cancer, accounting for about 85% of all cases. It typically grows and spreads more slowly than small cell lung cancer and includes several subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. NSCLC is often diagnosed in its later stages due to a lack of early symptoms, making it more challenging to treat. Treatment options for NSCLC include surgery, radiation therapy, chemotherapy, targeted therapy, and immunotherapy, depending on the cancer's stage and molecular characteristics. 

Akeso presented positive results for their bispecific antibody ivonescimab, besting Merck's anti-PD-1 drug Keytruda (pembrolizumab) as a frontline treatment for patients with advanced, PD-L1-positive non-small cell lung cancer in a Phase III trial. Ivonescimab targets both PD-1 and VEGF. In the study, it lowered the risk of disease progression or death by a great 49% compared with Keytruda in Chinese patients and is highly statistically significant.

On the other hand, we had disappointing news with AstraZeneca and Daiichi Sankyo’s Dato-DXd failing to significantly improve overall survival in a Phase III NSCLC trial. The investigational TROP2-directed antibody-drug conjugate (ADC) datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Nevertheless, the likelihood of approval remains high, though the FDA is now more likely to convene an advisory committee ahead of its target action date. 

Likewise, Gilead's Trodelvy triplet regimen showed underwhelming results. A combination of Trodelvy, Keytruda and carboplatin triggered 43.1% and 39% tumor response rates in treatment-naïve NSCLC patients with nonsquamous and squamous histologies, respectively, according to results from a Phase 2 EVOKE-02 trial. Trodelvy (sacituzumab govitecan-hziy) is a TROP2-directed ADC, while Keytruda is a humanized monoclonal antibody and PD-1 inhibitor.