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Participants with CML or ALL, from Novartis sponsored asciminib studies, including but not limited to ABL001A2301, ABL001A2302, ABL001X2101, ABL001A2202, ABL001AUS04 and ABL001AUS08 studies, that were receiving asciminib

Participants with CML-CP, from Novartis sponsored asciminib study ABL001A2301, that were receiving bosutinib

Participants with CML-CP, from Novartis sponsored asciminib study ABL001A2301 that were receiving bosutinib treatment and switched to asciminib when entering this study or during the course of this study

Participants with CML from Novartis sponsored asciminib studies ABL001E2201 or CABL001X2101 that were receiving asciminib combined with imatinib

Participants with CML or ALL from Novartis sponsored asciminib studies ABL001E2201or CABL001X2101 that were receiving asciminib combined with nilotinib

Participants with CML-CP, from Novartis sponsored asciminib study ABL001E2201 that were receiving imatinib

Participants with CML-CP, from Novartis sponsored asciminib study ABL001E2201 that were receiving nilotinib

Participants with CML from Novartis sponsored study ABL001X2101 that were receiving asciminib with dasatinib

Taken orally, twice daily (BID) or once daily (QD), in fasting state

Asciminib single agent

Taken orally, once daily, in the morning with low-fat meal or twice daily in fasting state

Taken orally, once daily, in the morning with low-fat meal

Imatinib

Taken orally, twice daily, on an empty stomach

Taken orally, once daily in a fasted state, 1 or 2 hours before a meal

Novartis Pharmaceuticals

Moshe Talpaz

Dalisa Espinosa

Michael Mauro

Koji Sasaki

This is a long term safety study for patients who have completed a Novartis sponsored asciminib study and are judged by the investigator to benefit from continued treatment

This is an open-label, multi-center, global roll-over study designed to assess long term safety and provide continued treatment to participants who have previously participated in an asciminib Novartis sponsored study and who, in the opinion of the investigator, would benefit from continued treatment as in the parent study, or from switching to asciminib (if they were on bosutinib in the parent study), but are unable to access this treatment outside of the clinical study.

Asciminib Roll-over Study

An Open Label, Multi-center Asciminib Roll-over Study to Assess Long-term Safety in Patients Who Have Completed a Novartis Sponsored Asciminib Study and Are Judged by the Investigator to Benefit From Continued Treatment

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

All AEs and SAEs will be tabulated and listed for participants in the Safety Set by treatment group. From day of first administration of study treatment to 30 days after the last study treatment.

Investigators' assessment of clinical benefit will collected through the Investigator confirming that the patient is still benefiting from treatment. This will be evaluated and tabulated for participants in the Safety Set by treatment group at each visit.

Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily

Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily

Asciminib 60 mg or 40 mg taken orally once daily.

Asciminib add-on

Nilotinib 300 mg taken orally twice daily (total daily dose of 600 mg)

To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib versus asciminib 80mg in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)

The study is a Phase 2, multi-center, open-label, randomized study of asciminib in two different doses (40 mg or 60 mg) in combination with imatinib 400 mg versus continued imatinib versus switch to nilotinib, versus asciminib 80mg single agent in subjects with chronic myeloid leukemia in chronic phase (CML-CP) who have been previously treated with imatinib first line therapy for at least one year and have not achieved deep molecular response (DMR). Eighty-four eligible subjects were randomized 1:1:1:1 to receive asciminib 60 mg once daily (QD) as add-on therapy to imatinib 400 mg QD, or 40 mg QD as add-on therapy to imatinib 400 mg QD, or to continue imatinib 400 mg QD, or to switch to nilotinib 300 mg twice a day (BID).

The asciminib single agent cohort will be conducted as an open label cohort. Approximately 20 eligible subjects will be enrolled to receive asciminib 80 mg QD. Amendment 3 aims to add the asciminib single agent cohort to assess whether asciminib single agent at the recommended dose of 80mg QD leads to similar efficacy and safety as observed in the add-on arms of asciminib and imatinib. This additional cohort will help to evaluate if the combination of asciminib with imatinib is needed to increase the likelihood of achieving DMR, or if this can be achieved by asciminib alone.

An interim analysis was performed to gain an early insight into the safety and efficacy of the asciminib add-on combination. The interim analysis was planned to be performed when at least 40 (50%) patients have been randomized and have been followed for their 24 weeks visit assessment or have discontinued treatment. The interim analysis cut-off was on 22-July-2020. No change in study conduct were performed based on the benefit/risk balance.

The primary analysis cut-off was on 10-Jan-2022. Eighty-four patients have been randomized in the study.

Subjects on the imatinib continuation arm who had not achieved MR4.5 at 48 weeks were allowed to cross-over (CO) to receive the add-on treatment within 4 weeks after week 48 visit. to receive the asciminib 60 mg combination add-on treatment, as this dose provided higher exposure. The cross-over is at the discretion of the investigator and the patient. Apart from a polymerase chain reaction (PCR) result of below MR4.5 at Week 48 visit, there are no other entry criteria for the cross-over part. Subjects on nilotinib are not allowed to cross- over to receive the add-on treatment.

Subjects on the study will continue on the allocated treatment until treatment failure, intolerability, or for up to 96 weeks (in arms 1 to 4) / or 48 weeks (in asciminib single agent cohort) after the last randomized subject received the first dose of treatment. After the last dose received, every subject will be followed up for safety for 30 days.

Treatment arms 1 - 4 randomized; New Treatment arm 5 (asciminib single agent cohort) not randomized

Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

A Phase 2, Multi-center, Open-label, Randomized Study of Oral Asciminib Added to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients With CML-CP Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Percentage of subjects still treated with the randomized treatment at 48 weeks and are in MR4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks (± assessment window), among all subjects randomized to the respective treatment arm.

Percentage of subjects with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib

Difference in the percentage of subjects with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib

Percentage of subjects with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks

Best observed rate of MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) under randomized treatment up to the specific time point

Percentage of participants who are in MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks and who have no loss of MR\^4.5.

Time to MR\^4.5 is the time from randomization to first MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) computed only for subjects who achieved MR\^4.5

Time from first MR\^4.5 until loss of MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%).

To characterize the safety and tolerability profile of asciminib 60 mg or 40 mg + imatinib vs continued imatinib or switch to nilotinib or asciminib 80mg QD

The maximum (peak) observed drug concentration after dose administration

The time to reach maximum (peak) drug concentration after dose administration

The AUC from time zero to the last measurable concentration sampling time (Tlast)

The AUC calculated to the end of a dosing interval (tau) at steady-state

The percentage of subjects on asciminib 80mg QD with MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks

For subjects on asciminib 80mg QD: Time to MR\^4.5 is the time from randomization to first MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) computed only for subjects who achieved MR\^4.5

Time from first MR\^4.5 until loss of MR\^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) for subjects on asciminib 80mg QD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Asciminib Roll-over Study	NCT04877522	Chronic Myeloge... Leukemia, Myelo...	Asciminib singl... Asciminib Imatinib Nilotinib Bosutinib Dasatinib	18 Years -	Novartis
Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)	NCT03578367	CML Chronic Myeloge... Leukemia, Myelo... Hematologic Dis...	Asciminib add-o... Imatinib Nilotinib Asciminib singl...	18 Years -	Novartis
Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)	NCT03578367	CML Chronic Myeloge... Leukemia, Myelo... Hematologic Dis...	Asciminib add-o... Imatinib Nilotinib Asciminib singl...	18 Years -	Novartis
Asciminib Roll-over Study	NCT04877522	Chronic Myeloge... Leukemia, Myelo...	Asciminib singl... Asciminib Imatinib Nilotinib Bosutinib Dasatinib	18 Years -	Novartis

Spots Global Cancer Trial Database for asciminib single agent