Dr Simon on the ALK Inhibitor Selection Process in ALK+ NSCLC 

George R. Simon, MD, FACP, FCCP, senior member, Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center, delineates the process of selecting appropriate ALK inhibitors for the treatment of patients with 

-positive non–small cell lung cancer(NSCLC).

Simon begins by highlighting alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena), which are all approved by the FDA for the treatment of patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test. He also points to ensartinib (X-396), which is 

 for the treatment of patients with metastatic 

-positive NSCLC. Notably, on April 18, 2024, 

the regulatory agency expanded the indication for alectinib

 when it approved the agent for use as adjuvant treatment following tumor resection in patients with ALK-positive NSCLC whose tumors are at least 4 cm or node positive.

When selecting an ALK inhibitor in the metastatic setting, Simon notes that the decision-making process is multifaceted, including the consideration of patient-specific factors such as baseline health. Potential resistance mechanisms can be associated with each of the approved ALK inhibitors; however, alternative medications can sometimes counteract these mechanisms, Simon explains. The known safety profile of each agent is also discussed when selecting between these agents, Simon adds.

Furthermore, when choosing an ALK inhibitor for eligible patients with metastatic NSCLC, it is crucial to account for the specific genetic mutation or alteration detected in an individual patient, Simon continues. For example, in patients with 

 G1202R mutations, lorlatinib has been the only agent associated with efficacy in this subgroup, Simon explains. Determining the specific 

 alteration and consulting a treatment algorithm to match mutations with corresponding sensitive drugs can help facilitate personalized treatment plans for individual patients, Simon emphasizes.

Simon underscores the importance of individualized therapy selection in ALK inhibitor treatment. By integrating patient health status, known resistance mechanisms, drug toxicities, and mutation-specific sensitivities, oncologists can optimize treatment for patients with 

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George R Simon, MD, FACP, FCCP on selecting ALK inhibitors in ALK-positive non–small cell lung cancer.

George Simon, MD, FACP, FCCP, chair, Department of Medical Oncology, Advent Health, department chair, Medical Oncology, Moffit Cancer Center, discusses the evaluation of datopotamab deruxtecan (DS-1062) in TROP-2–overexpressing solid tumors. 

The phase 1 TROPION-PanTumor01 trial (NCT03401385) evaluated the safety and tolerability of the TROP-2–targeting antibody-drug conjugate (ADC), datopotamab deruxtecan.

The goal of the study was to understand how TROP-2–overexpressing solid tumors reacted to datopotamab deruxtecan, Simon adds. 

The trial served as a preliminary step before ADC is evaluated in combination with other therapies and against the current standard of care, Simon continues. The phase 1 study will inform a more detailed portfolio of studies that will come down the line, Simon concludes.

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George Simon, MD, FACP, FCCP, discusses the evaluation of datopotamab deruxtecan in TROP-2–overexpressing solid tumors.


George R. Simon, MD

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Dr Simon on the ALK Inhibitor Selection Process in ALK+ NSCLC

Dr. Simon on the Evaluation of Datopotamab Deruxtecan in TROP-2–Expressing Solid Tumors