Expert Takeaway From WCLC Congress Highlights Innovative ADC Showing Promise in SCLC

Robert L. Ferris, MD, PhD, Lineberger distinguished professor, executive director, UNC Lineberger Comprehensive Cancer Center and chief of Oncology Services UNC Health System Chapel Hill, NC, highlights groundbreaking advancements presented by Charles Rudin, MD, PhD, the Sylvia Hassenfeld Professor and chief of Thoracic Oncology and co-director of the Druckenmiller Center for Lung Cancer Research at Memorial Sloan Kettering Cancer Center, at the recent World Congress on Lung Cancer held in San Diego, California.

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00:10 | From the World Congress on Lung Cancer, some exciting data were recently presented by Charles Rudin regarding an antibody drug conjugate [ADC], I believe is pronounced ifinatamab deruxtecan [I-DXd, DS-7300]. The deruxtecan is the payload, a type of chemotherapeutic attached to an antibody. It is a very common payload that can be attached to almost any antibody target. Depending on what the antibody is specific for, then it would apply to all types of different cancers.

00:46 | Rudin presented at the World Congress on Lung Cancer [the] targeting of [extended] stage SCLC, and this ifinatamab deruxtecan, which is an antibody drug conjugate, was tested at 2 different dose levels: 8 mg/kg and 12 mg/kg. The overall response rate by standard RESIST was quite impressive, about 26% at the 8 mg/kg and 56%, doubling, when they tested the 12 mg/kg. Thus, there was a dose response benefit with the agent. Interestingly, there may be the possibility to combine antibody drug conjugates with immunotherapy, because the type of tumor cell death based on the deruxtecan chemotherapy type payload may induce an immunogenic cell death.

01:45 | What attracted me to these approaches, an ADC or a bispecific, is that this modern protein engineering allows us to envision and conceive of different targets, identify targets, which has been a major effort for 20 or 30 years, since HER2 and herceptin [trastuzumab] 30 years ago. Now we have a whole shelf, a whole pipeline of different targets that we can mix and match specificities of these dual specific or bispecific antibodies.

02:20 | If you can imagine a strategy where the payload is on a single antibody, you could put a payload on a bispecific. You can have 1 or multiple targets with the bispecific antibody and begin adding chemotherapy-type payloads to induce tumor cell death, as well as immunogenic qualities and immune stimulation.

02:46 | Much like watching science fiction movies featuring crazy walkie-talkies and laser guns, the ability to create protein-engineered molecules with distinct front sides and back sides—each designed to target tumors and activate the body’s immune defenses—is truly amazing. It [shows] just how far we have come. And if you think just 3 to 5 years ago, all the advances, projecting another 3 to 5 years into the future, I think we are going to see a logarithmic expansion and growth of these exciting protein engineered targeted therapies.

For the full article from Ferris featuring his takeaways from WCLC, including new advancements in bispecific antibodies in NSCLC click HERE.