Amgen Explores First-Line Use of KRAS Inhibitor Lumakras in NSCLC Treatment

Amgen's Lumakras Shows Promise in First-Line NSCLC Treatment

Amgen is exploring the potential of its KRAS inhibitor, Lumakras (sotorasib), as a first-line treatment for patients with KRAS-mutated non-small cell lung cancer (NSCLC). This comes in response to a slowdown in the drug's uptake as a second-line therapy, prompting the company to investigate its efficacy in previously untreated patients.

Clinical Trial Results

Recent findings from the phase 1b CodeBreaK 101 trial, presented at the World Conference on Lung Cancer (WCLC), have shown promising results. The study involved 20 patients treated with Lumakras in combination with chemotherapy drugs carboplatin and pemetrexed. The results indicated that:

• 65% Objective Response Rate (ORR): Two-thirds of the patients experienced tumor shrinkage.
• 100% Disease Control Rate: All patients saw stabilization in tumor growth.

Davide Reese, Amgen's head of R&D, highlighted the significance of these findings, stating, "These results validate our approach to move Lumakras earlier within the treatment paradigm through novel therapeutic combinations."

Implications for KRAS-Mutated NSCLC

The trial also revealed a similar ORR of 62% in a subgroup of patients with KRAS-positive tumors and very low PD-L1 expression (<1%). These findings support earlier studies suggesting the efficacy of Lumakras combined with chemotherapy in treatment-naïve KRAS-mutated NSCLC.

Future Directions

Amgen has initiated a phase 3 study, CodeBreaK 202, to further evaluate the triple therapy's effectiveness in first-line KRAS-mutant PD-L1-negative advanced NSCLC. Enrollment for this study is expected to commence by the end of 2023.

Market and Strategic Considerations

Despite the promising clinical data, Lumakras's sales plateaued at $77 million in the second quarter of 2023. This stagnation has tempered analysts' expectations for the KRAS inhibitor market. However, expanding Lumakras's label to include first-line NSCLC treatment could rejuvenate its market performance and solidify its role in Amgen's growth strategy.

Conclusion

The exploration of Lumakras as a first-line treatment for KRAS-mutated NSCLC represents a significant shift in the therapeutic landscape. With ongoing clinical trials and promising early results, Amgen is poised to potentially redefine the standard of care for this challenging cancer subtype.