Phase III Trial Data for Scemblix Show Clinically Meaningful Response in Chronic Myeloid Leukemia

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Findings from the Phase III ASC4FIRST (NCT04971226) trial show that Novartis’ Scemblix (asciminib) plus investigators’ choice of tyrosine kinase inhibitor (TKI) produced positive results in patients newly diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Both of the primary endpoints for the trial of major molecular response (MMR) rate for Scemblix vs. investigator-selected TKIs—either imatinib, nilotinib, dasatinib, and bosutinib compared to imatinib—showed clinically meaningful and statistically significant data.¹

“We are very encouraged by these results given that a significant proportion of patients with newly diagnosed chronic myeloid leukemia, or CML, do not achieve their treatment goals,” prof. Tim Hughes, MD, South Australian Health & Medical Research Institute, said in a press release.¹ “There remains a significant need in first-line therapy of CML for tolerable treatment options, allowing people with CML to balance their treatment alongside their quality of life.”

CML is a rare myeloproliferative disorder comprising approximately 15% of total leukemia cases.² Therapeutic advances have altered the landscape for patients with CML, as it has become a chronic disease that has a life expectancy comparable to the general population, which subsequently means tolerability is a key goal of treatment, according to Novartis. Despite the benefit that patients with CML gain from current TKI therapies, the prevalence of intolerance and adverse events (AEs) has led to discontinuation rates related to AEs of up to 25% by five years. Further, more than 60% of patients who are newly diagnosed with CML are unable to achieve 12-month molecular response goals.¹

Scemblix has been shown to have a unique mechanism of action as a STAMP inhibitor of BCR-ABL1, which produces activity in patients with CML with resistance or intolerance to prior therapies. The FDA approved Scemblix in October 2021 for patients with CP-CML previously administered two or more TKIs and for adults with CP-CML with the T315I mutation based on findings from the CABL001X2101 and ASCEMBL trials (NCT02081378 and NCT03106779).³

The head-to-head, multi-center, open-label, randomized ASC4FIRST trial compared oral Scemblix 80 mg QD vs. investigator-selected first- or second-generation TKI among 405 adults with newly diagnosed Ph+ CML-CP1. The ongoing trial’s primary endpoints evaluated the efficacy of Scemblix compared with TKIs within the stratum of patients with imatinib as pre-randomization selected TKI, based on proportion of those who achieve MMR at week 481.

The trial’s key secondary endpoint is proportion of patients who achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE by week 96. Investigators are also analyzing additional secondary safety and efficacy endpoints, such as MMR, MR4, MR4.5, complete hematological response and BCR::ABL1 ≤1% at and by all scheduled data collection time points; duration of and time to first MMR, MR4, and MR4.5; time to treatment failure; event-free survival, failure-free survival, progression-free survival, and overall survival.¹

Novartis stated that trial data will be presented at an upcoming medical conference and included as part of regulatory submissions this year.

“We are excited that Scemblix may help people newly diagnosed with CML achieve their treatment goals while continuing to live their lives,” Novartis President, Development and Chief Medical Officer Shreeram Aradhye, MD, said in a press release.¹ “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.”

References

1. Novartis Scemblix® shows superior major molecular response (MMR) rates vs. standard‐of‐care TKIs in Phase III trial for newly diagnosed patients with chronic myeloid leukemia. Novartis. News release. January 8, 2024. Accessed January 8, 2024. https://www.novartis.com/news/media-releases/novartis-scemblix-shows-superior-major-molecular-response-mmr-rates-vs-standard-care-tkis-phase-iii-trial-newly-diagnosed-patients-chronic-myeloid-leukemia

2. Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. Am J Hematol. 2020;95(6):691-709. doi:10.1002/ajh.25792. Accessed January 8, 2024.

3. Scemblix. Prescribing information. Novartis; 2021. Accessed January 8, 2024. https://tinyurl.com/5epcyv83