Advancing to Phase 3 Designs for Advanced NSCLC

Photo Credit: Dzmitry Dzemidovich

At the 2023 North American Conference on Lung Cancer, held December 1-3 in Chicago, Karen L. Reckamp, MD, presented “Rechallenging with Immunotherapy” as part of the“Immunotherapy for Advanced NSCLC”session.

Dr. Reckamp recently co-authored a paper that addresses the need for cautious progression from phase 1 to phase 3 trials for advanced NSCLC, which we summarize here: 

Moving Toward Rationale Phase 3 Designs for Advanced NSCLC

 J Thorac Oncol. 2023 Dec;18(12):1629-1631. 

Summary: While immune checkpoint inhibitors (ICIs) have transformed advanced NSCLC treatment, challenges persist with tumor resistance, prompting exploration of combination therapies; however, the expedited progression from phase 1 safety assessment to phase 3 trials poses complexities in addressing unmet needs. Despite initial promise, a phase 3 trial evaluating bintrafusp alfa, a bifunctional fusion protein inhibiting both programmed death-ligand 1 (PD-L1) and the transforming growth factor β (TGF-β) pathways, was discontinued early in the first-line setting for advanced NSCLC with high PD-L1 expression. The study showed a non-significant increase in progression-free survival with bintrafusp alfa compared to pembrolizumab, but raised concerns with higher treatment-related adverse events, leading to early discontinuation. The results underscore the challenges of ICI combination therapies, emphasizing the need for cautious progression from phase 1 to phase 3 trials and the importance of diverse patient representation in clinical studies to ensure equitable outcomes in oncology research.