The emergence of bispecific antibodies (BsAbs) is marking a significant advancement in lung cancer treatment, with over 100 such therapies currently in clinical development. Unlike traditional monoclonal antibodies that target single antigens, these next-generation therapeutics can simultaneously bind to two different sites, potentially offering more comprehensive and durable treatment outcomes.
Amivantamab: A Dual-targeting Approach for NSCLC
Amivantamab (Rybrevant) represents a breakthrough in non-small cell lung cancer (NSCLC) treatment, specifically targeting both EGF and MET receptors on cancer cells. The drug's efficacy was definitively demonstrated in the phase 3 MARIPOSA trial, which enrolled more than 1,000 patients. The combination of amivantamab with lazertinib achieved a median progression-free survival of 23.7 months, significantly outperforming osimertinib's 16.6 months. The response durability was equally impressive, with a median duration of 25.8 months compared to 16.8 months for osimertinib.
The FDA has approved amivantamab for multiple NSCLC indications, including first-line treatment in combination with lazertinib for patients with specific EGFR mutations (exon 19 deletion or exon 21 L858R substitution). The therapy is also approved in combination with chemotherapy for various disease stages and mutation profiles.
Tarlatamab: New Hope for Small Cell Lung Cancer
Tarlatamab (Imdelltra) has emerged as a promising immunotherapy option for small cell lung cancer (SCLC), employing an innovative mechanism that bridges tumor cells and T cells. The drug specifically targets DLL3 on tumor cells and CD3 on T cells, facilitating immune-mediated tumor destruction.
The DeLLphi-301 trial, which led to FDA approval, demonstrated tarlatamab's effectiveness in heavily pretreated patients. Among 220 participants who had received a median of two prior treatment lines, the drug achieved a 40% objective response rate at 10 months. The durability of response was particularly noteworthy, with 68% of responders maintaining their response at 6 months and 40% beyond 12 months.
Clinical Implementation and Safety Considerations
Both therapies require careful management of potential adverse events. Amivantamab's administration protocol includes weight-based dosing and split initial infusions to minimize infusion-related reactions. Common side effects include elevated hepatic enzymes, fatigue, and musculoskeletal pain.
Tarlatamab requires close monitoring, particularly during initial doses, with patients needing 22-24 hours of observation after their first infusions. The dosing schedule begins with 1 mg intravenously on cycle 1, day 1, followed by 10 mg doses on specific intervals. Healthcare providers must be vigilant for cytokine release syndrome, neurotoxicity, and other potential adverse events.
These advancements are particularly significant for SCLC patients, who historically face limited treatment options and poor outcomes in later therapy lines. The durability of response observed with tarlatamab offers new hope for this challenging disease setting.
