Andreas Hochhaus, MD, Comprehensive Cancer Center of Jena University Hospital, Jena, Jena, Germany, discusses results from the phase 3 ASC4START trial which evaluated the tolerability of asciminib compared with nilotinib among patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP).

The results of this analysis demonstrated superior tolerability for patients with CML-CP treated with asciminib versus nilotinib. Dr Hochhaus stated, “Overall, this study demonstrates again after ASC4FIRST that asciminib is a drug of choice for treatment of first-line patients with CML in chronic phase.”

Transcript:

My name is Andreas Hochhaus. I am the director of the Comprehensive Cancer Center of the Jena University Hospital in Jena, Germany. On behalf of my colleagues from 120 centers in 24 countries worldwide, it's my pleasure to report at this meeting at ASCO 2025, for the first time, the interim analysis of the ASC4START study.

ASC4START has been designed to treat patients with chronic myeloid leukemia in chronic phase, first-line with asciminib versus nilotinib to demonstrate tolerability of the drug. For the first time, we introduced a new end point in this study—that's time to treatment discontinuation for adverse events. The impact of first-line asciminib treatment has been demonstrated with the ASC4FIRST study, which was published in the New England Journal of Medicine in 2024, but now we want to focus more on the tolerability of the drug.

Asciminib is a BCR-ABL-specific inhibitor. It does not inhibit other kinases. It is therefore BCR-ABL-specific, and therefore has less impact on side effects because side effects are mainly produced by the inhibition of off-target kinase. This was the expectation and already demonstrated in the phase 1 and also in the registration trial for third-line treatment.

Now in this study, we treated 568 patients randomized to asciminib versus nilotinib. We expected for the interim analysis, 46 events, that means discontinuations due to adverse events, but actually the interim analysis was performed after 50 events. Therefore, we have the power in the background, and we demonstrated that 34 patients had to discontinue treatment in the nilotinib arm versus 16 in the asciminib arm. That means there's a clear advantage for asciminib for this discontinuation rate.

All other parameters, that means the adverse events in general, grades 2 and grade 3 adverse events, and also efficacy is advantageous for asciminib. We have seen very early responses, the 10% level by 3 months, but also major molecular responses and also deep molecular responses very early in the course of the disease after 12 weeks of treatment already. This will be presented here.

Overall, this study demonstrates again after ASC4FIRST that asciminib is a drug of choice for treatment of first-line patients with CML in chronic phase.

Source: 

Hochhaus A, Mahon FX, Brümmendorf TH, et al. Primary endpoint results of the phase 3b ASC4START trial of asciminib (ASC) vs nilotinib (NIL) in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP): Time to treatment discontinuation due to adverse events (TTDAE). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 6501.