Asciminib Delivers Superior Responses in Phase 3 Ph+ CML Trial

Microscopic images of red blood cells activated platelets and white blood cells are showcased in the photographs as a result of leukemia: © AkuAku - stock.adobe.com

Asciminib (Scemblix) demonstrated superior major molecular response (MMR) rates compared with standard-of-care tyrosine kinase inhibitors (TKIs) in patients with Philadelphia chromosome (Ph)-positive newly diagnosed chronic myeloid leukemia (CML), according to findings from the phase 3 ASC4FIRST trial (NCT04971226).¹

The study met its primary end point of MMR of asciminib at week 48 compared with investigator-selected TKIs including imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Sprycel), and bosutinib (Bosulif). Asciminib also demonstrated favorable safety and tolerability profiles, and patients on asciminib had fewer reported adverse events (AEs) and treatment discontinuations compared with patients on the investigator-selected TKIs. No new safety signals for asciminib were identified.

The next planned data readout is at week 96. More data will be presented at an upcoming medical conference and presented to regulatory authorities this year, according to Novartis, the manufacturer of asciminib.

“We are excited that [asciminib] may help people newly diagnosed with CML achieve their treatment goals while continuing to live their lives,” said Shreeram Aradhye, MD, president of development and chief medical officer, Novartis, in a press release. “Given the chronic nature of their condition, patients often need to be on TKI therapy for many years, so treatment options that are well tolerated and highly efficacious are crucial to support adherence. This study outcome builds on our 20-year legacy in CML innovation as we strive to continue to address the remaining unmet needs for people living with this blood cancer.”

About the ASC4FIRST Trial

ASC4FIRST is a phase 3, multi-center, open-label, randomized study of asciminib vs investigator-selected TKIs in patients with newly diagnosed Ph-positive CML. The primary end point is MMR at week 48, and the secondary end points include MMR at week 96, time to discontinuation of study treatment due to AEs, complete hematological response, complete cytogenic response at weeks 48 and 96, duration of MMR, time to first MMR, time to treatment failure, failure-free survival, event-free survival, progression-free survival, and overall survival.²

Patients in the experimental arm are receiving 80 mg of oral asciminib daily under fasting conditions. Patients in the active comparator arm are receiving either 400 mg of imatinib daily with food, 300 mg of nilotinib twice daily while fasting, 100 mg of dasatinib daily with or without food, or 400 mg of bosutinib daily with food.

Eligibility criteria includes a diagnosis of CMLO with cytogenetic confirmation of Philadelphia chromosome, an ECOG performance status of 0 or 1.5, adequate organ function, and evidence of typical BCR-ABL1 transcript at the time of screening. Patients are not eligible to participate in the trial if they have received previous CML treatment, have a known central nervous system infiltration, impaired cardiac function, history of a bleeding disorder unrelated to cancer, history of acute pancreatitis, or history of chronic liver disease.

REFERENCES:

1. Novartis Scemblix shows superior major molecular response (MMR) rates vs. standard-of-care TKIs in phase 3 trial for newly diagnosed patients with chronic myeloid leukemia. News release. Novartis. January 8, 2024. Accessed January 8, 2024. http://tinyurl.com/59v4yfxw

2. A study of oral asciminib versus other TKIs in adult patients with newly diagnosed PH+ CML-CP. ClinicalTrials.gov. Updated November 2, 2023. Accessed January 8, 2024. https://clinicaltrials.gov/study/NCT04971226