May 31, 2024
  • Phase III ASC4FIRST trial met both primary endpoints with clinically meaningful and statistically significant results; Scemblix® (asciminib) demonstrated superior MMR rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%)1
  • Scemblix also demonstrated a favorable safety and tolerability profile vs. imatinib and 2G TKIs, with fewer grade ≥3 AEs, dose adjustments, and half the rate of AEs leading to treatment discontinuation1
  • TKIs have transformed CML treatment, but unmet need remains; many newly diagnosed patients do not meet molecular response goals, and many discontinue or change treatment due to intolerance2-17
  • Scemblix was granted US FDA Breakthrough Therapy Designation, submission is now in review under the agency’s Oncology Center of Excellence RTOR program; data will be presented as a plenary at EHA and today as a late-breaking abstract at ASCO

East Hanover, May 31, 2024 – Novartis today presents positive results from the pivotal Phase III ASC4FIRST trial as a late-breaking abstract at the 2024 American Society of Clinical Oncology (ASCO) meeting. Scemblix® (asciminib) demonstrated superior major molecular response (MMR) rates at week 48 compared to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) imatinib, nilotinib, dasatinib and bosutinib, and compared to imatinib alone in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP)1. Scemblix also showed a numerical improvement in MMR at week 48 vs. second generation (2G) TKIs (nilotinib, dasatinib and bosutinib)1. Additionally, Scemblix demonstrated a favorable safety and tolerability profile, with fewer adverse events (AEs) and treatment discontinuations vs. both imatinib and 2G TKIs1.

“Scemblix is the first CML treatment to show significantly better efficacy compared to investigator-selected standard-of-care TKIs,” said Prof. Tim Hughes, MD, South Australian Health & Medical Research Institute (SAHMRI). “When you combine superior response with the excellent safety and tolerability profile of Scemblix, we have a very promising potential frontline option for newly diagnosed patients to support them in achieving their treatment goals.”

The median follow-up was 16.3 and 15.7 months for Scemblix and investigator-selected SoC TKIs, respectively1. Nearly 20% more patients treated with Scemblix achieved MMR at week 48 vs. investigator-selected SoC TKIs and nearly 30% more patients achieved MMR at week 48 vs. imatinib alone1. Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs and imatinib alone1.



Scemblix (n=201)

vs. investigator-selected SoC TKIs (n=204)

Imatinib stratumb
Scemblix (n=101)

vs. imatinib (n=102)

2G TKI stratumc

Scemblix (n=100) vs. 2G TKIs (n=102)

Primary endpoints

Week 48 MMR rates

67.7% vs. 49.0%

69.3% vs. 40.2%


Week 48 MMR Treatment difference (95% CI)



Adjusted 1-sided





Secondary endpointsd

Week 48 MMR rates

66.0% vs. 57.8%

Week 48 MR4

39% vs. 21%

43% vs. 15%

35% vs. 26%

Week 48 MR4.5

17% vs. 9%

18% vs. 5%

16% vs. 13%

a All patients receiving Scemblix (n=201) or investigator-selected SoC TKIs (n=204). Treatment difference after adjusting for pre-randomization selected TKI and EUTOS long-term survival (ELTS) risk groups at baseline.

b The 203 patients within the pre-randomization-selected imatinib stratum were randomized to receive either Scemblix (n=101) or imatinib (n=102). Treatment difference after adjusting for ELTS risk groups at baseline.

c The 202 patients within the pre-randomization selected 2G TKIs stratum were randomized to receive either Scemblix (n=100) or 2G TKIs (n=102: nilotinib, 48%; dasatinib, 41%; bosutinib, 11%).

d Secondary endpoints were not powered for statistical significance.

In newly diagnosed patients, the safety profile was consistent with previous registration studies with no new safety concerns observed1. Fewer grade ≥3 AEs, dose adjustments to manage AEs, and half the rate of AEs leading to treatment discontinuation were reported for Scemblix vs. both imatinib and 2G TKIs1.





Grade ≥3 AEsa




AEs leading to treatment discontinuationa




AEs leading to dose adjustments/ interruptionsa




a In patients who experienced ≥1 adverse event.

“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, M.D., President, Development and Chief Medical Officer, Novartis. “The compelling ASC4FIRST data highlight the potential of Scemblix to achieve better results than standard-of-care in newly diagnosed adults, while maintaining a favorable safety and tolerability profile. These results reinforce Scemblix as a proven treatment in Ph+CML-CP, as we continue to build on our 20-year legacy in CML innovation.”

“CML is a chronic condition and the side effects of standard-of-care 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. “Effective care that can be tolerated long-term is a key unmet need. By potentially bringing Scemblix 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.”  

The trial remains ongoing, with the next scheduled analysis at week 96 to evaluate the key secondary endpoint (MMR at week 96) and additional secondary endpoints18.

These results have been submitted to the US Food and Drug Administration (FDA) via the Oncology Center of Excellence Real-Time Oncology Review (RTOR) program and Scemblix has been granted Breakthrough Therapy Designation. They will also be presented as a plenary at the European Hematology Association (EHA) 2024 Congress in June.

About ASC4FIRST Phase III Clinical Trial
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix® 80 mg QD vs. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP18. The two primary endpoints of the study are to compare efficacy of asciminib vs. investigator-selected SoC TKIs and to compare efficacy vs. that of TKI within the stratum of participants with imatinib as pre-randomization selected TKI, based on proportion of patients that achieve MMR at week 4818.

The study remains ongoing with key secondary endpoints of proportion of patients that achieve MMR at week 96 and a safety endpoint of discontinuation of study treatment due to an AE (TTDAE) by week 9618. The study also assesses additional secondary safety and efficacy endpoints, including MMR, MR4, MR4.5, complete hematological response (CHR) 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 survival18.

SCEMBLIX® (asciminib) tablets is a prescription medicine used to treat adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with 2 or more tyrosine kinase inhibitor (TKI) medicines. The effectiveness of SCEMBLIX in these patients is based on a study that measured major molecular response (MMR) rates. No clinical information is available to show if these patients treated with SCEMBLIX live longer or if their symptoms improve. Ongoing studies exist to find out how SCEMBLIX works over a longer period of time.

SCEMBLIX is also approved for use in adults with Ph+ CML in CP with the T315I mutation.

It is not known if SCEMBLIX is safe and effective in children.

Important Safety Information
SCEMBLIX® (asciminib) tablets may cause low platelet counts (thrombocytopenia), low white blood cell counts (neutropenia), and low red blood cell counts (anemia). Patients should tell their doctor right away if they have unexpected bleeding or easy bruising; blood in their urine or stools; fever; or any signs of an infection. SCEMBLIX may increase enzymes in the patient's blood called amylase and lipase, which may be a sign of inflammation of the pancreas (pancreatitis). Patients should tell their doctor right away if they have sudden stomach-area pain or discomfort, nausea, or vomiting. During treatment with SCEMBLIX, doctors may check their patients' blood pressure and treat any high blood pressure as needed. Patients should tell their doctor if they develop elevated blood pressure or symptoms of high blood pressure including confusion, headaches, dizziness, chest pain, or shortness of breath.

If a patient has an allergic reaction while on SCEMBLIX, they should stop taking SCEMBLIX and get medical help right away. Signs or symptoms of an allergic reaction include trouble breathing or swallowing; feeling dizzy or faint; swelling of the face, lips, or tongue; fever; skin rash or flushing; or a fast heartbeat. SCEMBLIX may cause heart and blood vessel problems, including heart attack; stroke; blood clots or blockage of patient's arteries; heart failure; and abnormal heartbeat which can be serious and may sometimes lead to death. These heart and blood vessel problems can happen in people with risk factors or a history of these problems and/or previously treated with multiple TKI medicines. Patients should tell their doctor right away if they get shortness of breath; chest pain or pressure; a feeling like their heart is beating too fast or they feel abnormal heartbeats; swelling in their ankles or feet; dizziness; weight gain; numbness or weakness on one side of their body; decreased vision or loss of vision; trouble talking; pain in their arms, legs, back, neck, or jaw; headache; or severe stomach-area pain.

Before taking SCEMBLIX, patients should tell their doctor about all of their medical conditions, including if they have a history of pancreatitis; a history of heart problems; or blood clots in their arteries and veins (types of blood vessels). SCEMBLIX can harm an unborn baby. Women should tell their doctor right away if they become pregnant or think they may be pregnant during treatment with SCEMBLIX. Women who are able to become pregnant should have a pregnancy test before they start SCEMBLIX and should use effective birth control during treatment and for 1 week after the last dose of SCEMBLIX. Women should not breastfeed during treatment and for 1 week after their last dose of SCEMBLIX.

Patients should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. SCEMBLIX and other medicines may affect each other, causing side effects. The most common side effects of SCEMBLIX include nose, throat, or sinus (upper respiratory tract) infections; muscle, bone, or joint pain; rash; tiredness; nausea; and diarrhea. The most common blood test abnormalities include decreased blood counts of platelets, white blood cells, and red blood cells; and increased blood levels of triglycerides, creatine kinase, liver enzymes, or pancreas enzymes (amylase and lipase).

Please see full Prescribing Information for SCEMBLIX, available at

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