Dr Florez on Emerging Strategies to Address Checkpoint Inhibitor Resistance in NSCLC

“ADCs, vaccines, cell therapy, and anti-angiogenic combos are all very promising [strategies to overcome immune checkpoint inhibitor resistance].”

Narjust Florez, MD, the associate medical director of the Cancer Care Access Program and a thoracic medical oncologist at the Dana-Farber Brigham Cancer Center, a member of faculty at Harvard Medical School, and co-chair of the 2025 Bridging the Gaps in Lung Cancer meeting, discussed audience perspectives on emerging strategies to address immune checkpoint inhibitor (ICI) resistance in non–small cell lung cancer (NSCLC) during the meeting’s final polling session.

When asked about the most promising therapeutic approaches to overcome ICI resistance, audience responses varied by platform. On X, 50% of respondents favored anti-angiogenic combinations, whereas on LinkedIn, no respondents selected this option; instead, 50% identified cell therapies as the leading strategy. Florez attributed these discrepancies in part to small sample sizes, noting that the poll was closed within 15 minutes of opening.

Florez highlighted anti-angiogenic combinations as a particularly notable area of development, referencing the phase 3 HARMONi trial (NCT06396065) evaluating ivonescimab (SMT112), a bispecific antibody targeting PD-1 and VEGF, in combination with chemotherapy vs chemotherapy plus placebo.

Antibody-drug conjugates (ADCs) were also identified as a promising modality. According to Florez, successful integration of ADCs will depend on selecting the optimal patient population and ensuring that the linker and cytotoxic payload are appropriately matched to the tumor’s biology to maximize efficacy and minimize toxicity.

Therapeutic cancer vaccines remain in earlier stages of development, with ongoing efforts to refine antigen selection and immune priming strategies. Florez emphasized that these agents may require significant additional time before demonstrating a clinically meaningful benefit in NSCLC.

Cell-based therapies, including adoptive T-cell transfer and engineered T-cell receptor approaches, are advancing in parallel, offering the potential to circumvent mechanisms of ICI resistance through direct tumor targeting. Although these strategies remain largely investigational, their inclusion among top audience selections reflects growing interest in their potential role in treatment-refractory disease, she concluded.