Targeted therapies, including tyrosine kinase inhibitors, have transformed the treatment of late-stage non-small cell lung cancer (NSCLC). Kirsten rat sarcoma oncogene (KRAS) driver mutations occur in more than 25% of non-squamous NSCLC patients, but until recently, KRAS mutations were undruggable. Last May, Amgen ’s Lumakras (sotorasib) received accelerated US Food and Drug Administration (FDA) approval for the treatment of NSCLC patients harbouring the KRAS G12C mutation and having received at least one line of systemic therapy. GlobalData estimates that Lumakras is set to become a blockbuster agent in NSCLC.
In updated data from the Phase II CodeBreaK 100 trial submitted to the European Medicines Agency (EMA), Lumakras administration led to an objective response rate (ORR) of 37.1%, at a median duration of response of 11.1 months. Key opinion leaders (KOLs) interviewed by GlobalData expressed a preference for trying KRAS G12C inhibitors in combination with other agents to extend the progression-free survival (PFS) of patients. GlobalData forecasts that around 2,500 patients in the US will be treated with Lumakras this year, a number expected to rise to around 4,600 by 2029.
The closest competitor to Lumakras is Mirati Therapeutics’ adagrasib; in a Phase II KRYSTAL-1 trial, adagrasib demonstrated a similar ORR of 43% and PFS of 8.3 months in the same, pre-treated KRAS G12C patient population. With a new drug application (NDA) to the FDA imminent, adagrasib could reach the US market as early as next year. Lumakras’ first-mover advantage should give it great physician familiarity, but given the nature of accelerated approvals, updated long-term data could shift the balance in favour of either agent, especially if their safety profiles prove sufficiently different.
Lumakras also received EMA approval this month, putting it another step ahead of adagrasib and bolstering its prospects of achieving high commercial success. Both companies are, however, investigating their agents in label expansion trials in earlier lines of therapy, as well as in combination with other treatment modalities. As has been the case in other NSCLC patient populations, significant market dominance can be achieved after getting an early label expansion to first-line treatment, as well as to the adjuvant/neoadjuvant settings. GlobalData anticipates the delay in getting adagrasib to the market to result in an $822m difference in peak global sales by 2029, with Lumakras achieving $1.1bn and adagrasib $292m.