Recent data presented at the World Congress on Lung Cancer highlighted the potential of ifinatamab deruxtecan (I-DXd), an antibody-drug conjugate (ADC), in treating extensive-stage small cell lung cancer (ES-SCLC). The findings suggest a dose-dependent benefit, with higher doses of I-DXd demonstrating improved response rates.
Dose-Response Benefit of Ifinatamab Deruxtecan
Charles Rudin, MD, PhD, presented data on I-DXd, which consists of a chemotherapeutic payload (deruxtecan) attached to an antibody. The study evaluated two different dose levels of I-DXd: 8 mg/kg and 12 mg/kg. The overall response rate, assessed by standard RECIST criteria, was approximately 26% at the 8 mg/kg dose. Notably, the response rate nearly doubled to 56% when the 12 mg/kg dose was administered, indicating a clear dose-response relationship.
Potential for Combination with Immunotherapy
Researchers are also exploring the possibility of combining ADCs with immunotherapy. The mechanism of tumor cell death induced by the deruxtecan payload may trigger immunogenic cell death, potentially enhancing the effectiveness of immunotherapy agents when used in combination with I-DXd.
Advancements in Protein Engineering
The development of ADCs and bispecific antibodies represents a significant advancement in protein engineering. These technologies allow researchers to target specific tumor markers and deliver therapeutic payloads directly to cancer cells. Robert L. Ferris, MD, PhD, noted that these advancements enable the creation of protein-engineered molecules with distinct functionalities, designed to target tumors and activate the body's immune defenses.
The Evolving Landscape of Lung Cancer Treatment
The field of oncology is witnessing an explosion of novel payloads, antibody targeting strategies, and combination therapies. Bispecific antibodies, such as ivonescimab, are also being compared head-to-head with standard-of-care PD-1 and PD-L1 inhibitors in non-small cell lung cancer (NSCLC). These protein-engineered agents offer the potential to fine-tune treatment strategies and achieve objective improvements in clinical responses, marking a new era in targeted cancer therapy.
