FDA Grants Priority Review to Asciminib in Newly Diagnosed Ph+ CML

Supporting data for the priority review designation came from the phase 3 ASC4FIRST trial (NCT04971226) assessing asciminib compared with standard first- or second-generation tyrosine kinase inhibitors (TKIs) in the aforementioned population.

The FDA has granted priority review to asciminib (Scemblix) as a treatment for adults with newly diagnosed Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase (CML-CP), according to a press release from the developer, Novartis.¹

Supporting data for the priority review designation came from the phase 3 ASC4FIRST trial (NCT04971226) assessing asciminib compared with standard first- or second-generation tyrosine kinase inhibitors (TKIs) in the aforementioned population.

“We welcome the FDA’s decision to grant priority review and breakthrough therapy designations to [asciminib] for [patients with] newly diagnosed CML, which underscores the substantial need for additional effective, safe and tolerable treatment options,” Rodney Gillespie, senior vice president and therapeutic area head of United States Oncology at Novartis, stated in the press release.¹ “The ASC4FIRST data indicate that [asciminib], if approved, has the potential to address a critical gap in CML by offering a highly effective treatment along with a favorable safety and tolerability profile.”

According to data from ASC4FIRST presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the 48-week major molecular response (MMR) rate was 67.7% with asciminib vs 49.0% with standard TKIs, representing an 18.9% increase (95% CI, 9.6-28.2; P <.001).² In the imatinib (Gleevec) stratum of both arms, the 48-week MMR rates were 69.3% with asciminib-based treatment vs 40.2% with imatinib alone, conferring a 29.6% increase with asciminib (95% CI, 16.9%-42.2%; P <.001). Data showed that asciminib elicited higher MMR rates across all prespecified demographic and prognostic subgroups compared with standard TKIs.

Grade 3 or higher adverse effects (AEs) occurred in 38.0% of patients treated with asciminib, 44.4% of those who received imatinib alone, and 54.9% of those who received second-generation TKIs. AEs leading to treatment discontinuation were reported in 4.5%, 11.1%, and 9.8% of each respective group. Additionally, AEs resulting in dose adjustments or interruptions occurred in 30.0%, 39.4%, and 52.9%, respectively.

Any-grade hematologic toxicities in the asciminib, imatinib, and second-generation TKI groups, respectively, included thrombocytopenia (28.0% vs 28.3% vs 34.3%), neutropenia (25.0% vs 31.3% vs 34.3%), and anemia (11.5% vs 26.3% vs 22.5%). Other common non-hematologic toxicities in each respective group included diarrhea (15.5% vs 26.3% vs 25.5%), fatigue (14.0% vs 14.1% vs 17.6%), and headaches (13.5% vs 8.1% vs 21.6%).

“This is the first study to compare a new drug, in this case asciminib, with any of the TKIs that are approved in the frontline setting of chronic-phase CML. We demonstrated a statistically superior response in terms of MMR at 48 weeks, both against imatinib and against all TKIs, and a safety and tolerability profile that favors asciminib against all of the TKIs, suggesting that this strong benefit-risk profile may change the treatment paradigm in CML,” Jorge E. Cortes, MD, the director of the Georgia Cancer Center at Augusta University, said in a press briefing on these findings.²

In the head-to-head, multicenter, open-label ASC4FIRST trial, 405 adults with newly diagnosed Ph-positive CML-CP were randomly assigned to receive asciminib orally at 80 mg once daily or investigator-selected first- or second-generation TKIs. Standard TKIs included imatinib, nilotinib (Tasigna), dasatinib (Sprycel), and bosutinib (Bosulif).

The trial’s primary end points were MMR at week 48 for asciminib vs all investigator-selected TKIs and MMR at week 48 for asciminib vs investigator-selected TKIs within the imatinib stratum. Secondary end points currently under assessment include MMR at 96 weeks and discontinuation of study therapy due to AEs by week 96.

References

1. Novartis Scemblix® granted FDA priority review for the treatment of adults with newly diagnosed CML. News release. Novartis. July 29, 2024. Accessed July 30, 2024. https://tinyurl.com/2ap664kx
2. Hughes TP, Hochhaus A, Takahashi N, et al. ASC4FIRST, a pivotal phase 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): primary results. J Clin Oncol. 2024;42(suppl 17):LBA6500. doi:10.1200/JCO.2024.42.17_suppl.LBA6500