Asciminib Shows Superior Efficacy, Favorable Safety in Patients With Newly Diagnosed Chronic Myeloid Leukemia

Asciminib demonstrated stronger efficacy, safety, and tolerability, as well as less adverse events in patients compared with those who received investigator-selected standard-of-care tyrosine kinase inhibitors.

According to positive results from the phase 3 ASC4FIRST trial (NCT04971226), asciminib (Scemblix; Novartis) demonstrated a superior major molecular response (MMR) rate at week 48 in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Asciminib was compared with investigator-selected standard of care (SOC) tyrosine kinase inhibitors (TKIs)—imatinib, nilotinib, dasatinib, and bosutinib—and imatinib alone. According to the investigators, the findings will be presented as a plenary at the European Hematology Association 2024 Congress, which will be held June 13 to June 16.¹

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About the Trial

Trial Name: A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP

ClinicalTrials.gov ID: NCT04971226

Sponsor: Novartis Pharmaceuticals

Completion Date (Estimated): January 18, 2028

Asciminib is the first CML treatment that works by targeting the ABL myristoyl pocket—also known as a STAMP inhibitor—and currently approved treatments are TKIs which target the ATP-binding site. It is approved in over 70 countries for the treatment of Ph+ CML-CP in adult patients who received prior treatment with 2 or more TKIs, and in some countries, it is also approved in patients with the T315I mutation. Asciminib is an important treatment for those who are resistant or intolerant after 2 prior TKI therapies, and it is currently being studied as a monotherapy and combination therapy in patients with Ph+ CML-CP.^1,2

ASC4FIRST is a head-to-head, multicenter, open-label, randomized phase 3 trial that evaluated asciminib in patients with newly diagnosed Ph+ CML-CP. A total of 405 patients were randomly assigned to receive 80 mg of oral asciminib once per day (n = 201) or an investigator-selected TKI (n = 204) that includes 1 of the following treatments: 400 mg of imatinib once per day with food, 300 mg of nilotinib twice per day without food, 100 mg of dasatinib once per day either with or without food, and 300 mg of bosutinib once per day with food.^1,3

The trial’s 2 primary end points are to compare the efficacy of asciminib to investigator-selected standard-of-care (SOC) TKIs. The trial also compares the efficacy of asciminib with the TKI within the population of participants with imatinib as pre-randomization-selected TKI, based on the proportion of patients that achieve MMR at week 48. Secondary end points include progression-free survival, overall survival, MMR, MR4, MR4.5, complete hematological response, and BCR::ABL1 of 1% or less by all scheduled data collection time points, among others. According to the investigators, the study is currently evaluating key secondary end points of proportion of patients that achieve MMR at week 96 as well as discontinuation of study treatment due to an adverse event (TTDAE).^1-3

“[Asciminib] is the first CML treatment to show significantly better efficacy compared to investigator-selected SOC TKIs,” said Tim Hughes, MD, professor at South Australian Health & Medical Research Institute, in a news release. “When you combine superior response with the excellent safety and tolerability profile of [asciminib], we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals.”¹

Patients were evaluated at a median follow-up of 16.3 months and 15.7 months for asciminib and investigator-selected SOC TKIs, respectively. The findings demonstrated that nearly 20% of patients who were treated with asciminib achieved a MMR at week 48, compared with 30% of patients who received SOC TKIs. Patients who were treated with asciminib had also achieved deeper rates of MR4 and MR4.5 compared with those who received investigator-selected SOC TKIs or imatinib alone.¹

“Patients living with CML need efficacious and well-tolerated treatment options that help them achieve meaningful outcomes as they manage their chronic condition,” said Shreeram Aradhye, MD, president of development and chief medical officer at Novartis, in the news release. “The compelling ASC4FIRST data highlight the potential of [asciminib] to achieve better results than SOC in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce [asciminib] as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation.”¹

The trial also found that, in patients with newly diagnosed Ph+ CML-CP, the safety profile of asciminib was consistent with prior registration studies and demonstrated no new safety concerns. AEs that were grades 3 or higher were reported more frequently in those who received imatinib (44%) and 2G TKIs (55%) than those who received asciminib (38%). Additionally, there were more AEs that led to treatment discontinuation and dose adjustments or interruptions in the imatinib and 2G TKI groups than in the asciminib group (treatment discontinuation: 11%, 10%, and 5%, respectively; dose adjustments or interruptions: 39%, 53%, and 30%, respectively).^1,2

“CML is a chronic condition and the side effects of SOC can be challenging for patients. They often affect their daily life and can lead to high rates of treatment switching,” said Gerald Clements, CML caregiver, patient advocate, and Steering Committee Treasurer at CML Advocates Network, in the news release. “Effective care that can be tolerated long-term is a key unmet need. By potentially bringing [asciminib] to patients when they are first diagnosed, they may have an opportunity to be on a highly effective treatment while also maintaining their day-to-day from the start.”¹

References

1. Novartis. Novartis Scemblix® Phase III data first to show superior efficacy with a favorable safety and tolerability profile vs. standard-of-care TKIs in adults with newly diagnosed CML. News release. May 31, 2024. Accessed June 3, 2024. https://www.novartis.com/news/media-releases/novartis-scemblix-phase-iii-data-first-show-superior-efficacy-favorable-safety-and-tolerability-profile-vs-standard-care-tkis-adults-newly-diagnosed-cml

2. McGovern, G. Asciminib Demonstrated Better MMR Rates in Patients With Newly Diagnosed Ph+ CML-CP. Pharmacy Times. January 10, 2024. Accessed June 3, 2024. https://www.pharmacytimes.com/view/asciminib-demonstrated-better-mmr-rates-in-patients-with-newly-diagnosed-ph-cml-cp

3. A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP. ClinicalTrials.gov identifier: NCT04971226. Updated May 3, 2024. Accessed June 3, 2024. https://www.clinicaltrials.gov/study/NCT04971226