Phase 3 ASCEMBL Study Meets Primary End Point In Patients with CML

August 26, 2020

The study is evaluating asciminib in adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who were previously treated with 2 or more tyrosine-kinase inhibitors.

The phase 3 ASCEMBL study met its primary end point of statistically significant superiority in major molecular response (MMR) rate at the primary analysis date of 24 weeks for asciminib (ABL001) versus bosutinib (Bosulif), according to Novartis, the developer of the agent.1

The study is evaluating asciminib in adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) who were previously treated with 2 or more tyrosine-kinase inhibitors (TKIs). Notably, patients with failure or intolerance to the most recently administered TKI therapy were also included in the trial.

“Our ability to treat patients with TKIs changed CML care forever. However, the risk of disease progression is a reality for many patients – especially those who experience resistance to sequential TKI therapy or those who cannot adhere to treatment due to the daily impact of intolerable side effects,” John Tsai, MD, head of Global Drug Development and chief medical officer at Novartis, said in a press release. “We are incredibly grateful to the patients and investigators around the world who participated in this study. These results with asciminib are a testament to our commitment to further transform CML care – this time through [specifically targeting the ABL myristoyl pocket; STAMP] inhibition, by exploiting a natural regulatory mechanism of the ABL kinase.”

Novartis indicated that data from the ASCEMBL trial will be submitted for presentation at an upcoming medical meeting, and results will be shared with regulatory authorities. The FDA has already granted asciminib fast track designation in this disease setting.

Earlier studies of asciminib were presented during past annual meetings of the European Hematology Association, showing promising results with the use of asciminib.2

Specifically, preliminary results from a phase 1 trial of asciminib in combination with ATP-competitive TKI in heavily pretreated patients with Ph+ CML-CP showed that among patients who at baseline did not achieve BCR-ABL1 International Scale less than 1% by 48 weeks, 60% (9/15) achieved molecular response less than 1% in an asciminib-plus-imatinib arm, and 43% (6/14) and 56% (5/9) of patients achieved molecular response less than 1% in asciminib-plus-nilotinib and asciminib-plus-dasatinib arms, respectively.

Moreover, in evaluable patients without MMR at baseline by 48 weeks, 42% achieved MMR with asciminib plus imatinib with a median treatment exposure of 54.6 weeks, and 31% of patients treated with a combination of asciminib plus nilotinib and 36% of patients treated with asciminib plus dasatinib, respectively, achieved MMR.

Even further, no patients with MMR at baseline lost MMR due to any of the 3 combination therapies, and all combinations demonstrated tolerable safety profiles in heavily pretreated patients with CML.

References:

1. Novartis investigational novel STAMP inhibitor asciminib (ABL001) meets primary endpoint of Phase III chronic myeloid leukemia study [news release]. Basel. Published August 26, 2020. Accessed August 26, 2020. https://www.novartis.com/news/media-releases/novartis-investigational-novel-stamp-inhibitor-asciminib-abl001-meets-primary-endpoint-phase-iii-chronic-myeloid-leukemia-study

2. Novartis continues to innovate in CML with long-term treatment-free remission results following Tasigna® use and promising combination data with investigational compound asciminib (ABL001) [news release]. Basel. Published June 14, 2019. Accessed August 26, 2020. https://www.novartis.com/news/media-releases/novartis-continues-innovate-cml-long-term-treatment-free-remission-results-following-tasigna-use-and-promising-combination-data-investigational-compound