Precision Oncology, Bispecific Antibodies, and Next-Generation Targeted Therapies Are Reshaping NSCLC Care: With Chandler Park, MD; Stephen V. Liu, MD

In this episode of Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Stephen V. Liu, MD, the division chief of Hematology Oncology at MedStar Georgetown University Hospital, part of the MedStar Georgetown Cancer Institute, in Washington, DC.

Their discussion centered on the continued evolution of precision medicine in non–small cell lung cancer (NSCLC), highlighting advances in molecular testing, targeted therapies, immunotherapy, and emerging treatment strategies presented at the 2026 ASCO Annual Meeting. Drs Park and Liu explored how lung cancer has become a model for precision oncology and emphasized that therapeutic advances across multiple tumor types have collectively shaped the current treatment landscape. They discussed the importance of understanding oncogenic drivers, overcoming resistance mechanisms, and moving effective therapies into earlier-stage disease to improve long-term patient outcomes.

A major focus of the conversation was the phase 3 LIBRETTO-432 trial (NCT04819100) evaluating adjuvant selpercatinib (Retevmo) in patients with completely resected RET fusion–positive NSCLC. Dr Liu described the findings as immediately practice changing, citing the substantial improvement in event-free survival observed with adjuvant targeted therapy. He explained that the study reinforces the growing role of comprehensive next-generation sequencing (NGS) for all patients with resected NSCLC, noting that molecular testing is now essential to identify patients who may benefit from adjuvant EGFR-, ALK-, or RET-directed therapies. The experts also discussed the challenge of detecting early-stage lung cancers in patients without a smoking history, emphasizing the need for new screening strategies and greater research into the causes of oncogene-driven lung cancers that frequently fall outside current screening recommendations.

The discussion then shifted to the next generation of immunotherapy, focusing on bispecific antibodies targeting PD-1/PD-L1 and VEGF. Dr Liu reviewed encouraging data from studies evaluating ivonescimab (SMT112) and other investigational agents, highlighting improvements in progression-free survival and overall survival in advanced squamous NSCLC and noting that these agents also maintain a manageable safety profile. The experts examined the potential for these agents to replace conventional checkpoint inhibitors by enhancing antitumor immune responses through cooperative binding and stressed the importance of careful patient selection, particularly for those at increased risk of bleeding complications.

Drs Park and Liu also explored the evolving treatment landscape for KRAS-mutant NSCLC, discussing the investigational combination of divarasib (GDC-6036) plus pembrolizumab (Keytruda) in the phase 1b/2 Krascendo-170 Lung study (NCT05789082). Dr Liu emphasized that although the regimen has generated promising response rates, the key consideration remains preserving the long-term benefit of immunotherapy by minimizing treatment-related toxicities that could require discontinuation of checkpoint inhibition. He contrasted the differing roles of immunotherapy across molecular subtypes, noting that patients with tumors driven by EGFR, ALK, and ROS1 alterations generally derive less benefit from current checkpoint inhibitors than those with KRAS-mutated disease, underscoring the importance of tailoring treatment according to individual tumor biology.

The conversation concluded with highlights from several additional ASCO 2026 presentations that may further reshape the treatment paradigm. Dr Liu discussed the landmark 7-year follow-up from the phase 3 CROWN trial (NCT03052608) of lorlatinib (Lorbrena), which yielded durable disease control and sustained intracranial efficacy in patients with ALK-positive NSCLC. He also highlighted encouraging findings with the fourth-generation ALK inhibitor neladalkib (NVL-655), as well as data from the phase 2 NEOLORA study (NCT06682884), which showed high pathologic complete response rates with lorlatinib before surgery. Beyond the efficacy results, Dr Liu emphasized the scientific value of analyzing residual tumor tissue following neoadjuvant therapy to better understand resistance mechanisms and identify future combination strategies that could improve outcomes in both early-stage and metastatic disease.