2024 Hot Topic in Basic & Translational Science: Tolerance & Resistance to Targeted Therapy in NSCLC - Posters-PP01.03: Characterization of Mutated KRAS Genotype and Clinical Outcomes in Patients With Advanced NSCLC Treated With Mecbotamab Vedotin, a CAB-AXL-ADC

PP01.03: Characterization of Mutated KRAS Genotype and Clinical Outcomes in Patients With Advanced NSCLC Treated With Mecbotamab Vedotin, a CAB-AXL-ADC

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The study presented at the IASLC 2024 conference in Washington, D.C., focused on evaluating the efficacy and safety of mecbotamab vedotin (Mec-V), a new antibody-drug conjugate, in patients with non-small cell lung cancer (NSCLC) featuring KRAS mutations. Mec-V targets the AXL receptor, often overexpressed in KRAS-mutated tumors, potentially leading to resistance against traditional treatments.<br /><br />Key findings highlighted that Mec-V was well-tolerated with a manageable safety profile, showing notable antitumor responses across multiple KRAS variants. The trial involved 78 patients with advanced, AXL-positive NSCLC, who had previously undergone significant treatment, including anti-PD-(L)1 therapies. Out of the 24 patients with KRAS mutations, the objective response rate was approximately 28.6%, with one patient maintaining a complete response for over two years.<br /><br />Mec-V's efficacy was underscored by the median overall survival (mOS) in the mKRAS subgroup, which remains unreached but was noted to be extended, contrasting with 8.7 months for wild-type KRAS (wtKRAS) patients. Previous studies reported modest mOS figures of about 11.3 months with therapies like docetaxel.<br /><br />Overall, the study suggests Mec-V could be a significant therapeutic option for KRAS-mutated NSCLC, especially for the heavily pretreated, treatment-refractory population. The promising results from the exploratory analysis support the forthcoming randomized trial comparing Mec-V against standard care for patients with mKRAS NSCLC. The study was funded by BioAtla, Inc., and supported by additional research partners and contributors. While common adverse events included fatigue and diarrhea, no grade 5 related adverse events were reported. Further research and longer follow-ups are in progress to consolidate these findings.

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Julia Rotow

Keywords

IASLC 2024

mecbotamab vedotin

NSCLC

KRAS mutations

AXL receptor

antibody-drug conjugate

objective response rate

median overall survival

treatment-refractory

BioAtla