Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Amino Acids

Asciminib

Bosutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients were randomized to asciminib 40mg BID

Patients were randomized to bosutinib 500mg QD

40 mg tablets was taken orally twice a day (BID)

500 mg tablets was taken orally once daily (QD)

Novartis Pharmaceuticals

The purpose of this pivotal study was to compare the efficacy of asciminib (ABL001) with that of bosutinib in the treatment of patients with CML-CP having previously been treated with a minimum of two prior ATP-binding site TKIs.

Patients intolerant to the most recent TKI therapy must have had BCR-ABL1 ratio \> 0.1% IS at screening and patients failing their most recent TKI therapy must have met the definition of treatment failure as per the 2013 European LeukemiaNet (ELN) recommendations.

Patients with documented treatment failure as per 2013 ELN recommendations while on bosutinib treatment had the option to switch to asciminib treatment within 96 weeks after the last patient has been randomized on study.

Patients were randomized in a 2:1 ratio to asciminib 40 mg BID or bosutinib 500 mg QD. Randomization was stratified by major cytogenetic response (MCyR) at screening. Patients with documented treatment failure (specifically meeting lack of efficacy criteria adapted from the 2013 ELN recommendations) while on bosutinib treatment were offered the option to switch to asciminib treatment within 96 weeks after the last patient was randomized to the study.

Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs

A Phase 3, Multi-center, Open-label, Randomized Study of Oral ABL001 Versus Bosutinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors

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

MMR was defined as a ≥ 3.0 log reduction in BCR-ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1% BCR-ABL1/ABL% by IS as measured by RQ-PCR.

To compare additional parameters of the efficacy asciminib versus bosutinib

To compare additional parameters of the efficacy of asciminib versus bosutinib. Cytogenic response will include Complete, Partial, Major, Minor, Minimal and no response.

To compare additional parameters of the efficacy of asciminib versus bosutinib

To characterize the PK of asciminib in the CML-CP population

Adverse Event (AE): Any sign or symptom that occurs during treatment plus 30 days after study treatment discontinuation.

Adverse events were analyzed in the Safety analysis set, which comprises all patients who received at least one dose of study treatment.

Patients randomized to asciminib 40mg BID

Patients randomized to bosutinib 500mg QD

Total

Age, Continuous

Sex: Female, Male

White

Asian

Black or African American

American Indian or Alaska Native

Other

Unknown

Race/Ethnicity, Customized

Full Analysis Set (FAS): The FAS comprised of all randomized patients.

In the asciminib arm, 2 patients died on-treatment and 2 patients died during survival follow-up. In the bosutinib arm, 1 patient died on-treatment.

Clinical Disclosure Office

Number of Participants With Major Molecular Response (MMR) Rate at 24 Weeks

Number of Participants With Major Molecular Response (MMR) Rate

Complete Cytogenetic Response Rate

Time to MMR

Duration of MMR

Time to CCyR

Duration of CCyR

Time to Treatment Failure

Progression Free Survival

Overall Survival

Trough Plasma Concentrations

PK Parameter: Cmax,

PK Parameter: Tmax

PK Parameter: AUC0-12h

PK Parameter: CL/F

Overall Study

Patients will receive asciminib (40 mg BID continuous)

Patients will receive best available therapy chosen by investigator

Asciminib comes in 20 mg and 40 mg tablets and is taken orally twice daily

asciminib

Best available treatment will be based on investigator's choice identified prior to randomization. Dose and frequency will depend on label and institutional guidelines for various BAT

best available treatment

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of asciminib versus best available therapy in Chinese patients with Chronic Myelogenous Leukemia in chronic phase, previously treated with 2 or more tyrosine kinase inhibitors to support related indication registration in China.

The primary objective of the study is to evaluate the Major Molecular Response (MMR) rate of asciminib treatment at 24 weeks.

The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of asciminib versus best available therapy (BAT) in Chinese patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) to support related indication registration in China.

This study will enroll the participants 1) who failed their most recent TKI therapy by meeting the definition of treatment failure as per the 2013 European Leukemia Net (ELN) guidelines, or 2) who were intolerant to the most recent TKI therapy and must have BCR-ABL1 ratio \> 0.1% IS at screening.

Eligible participants will be randomized into asciminib arm or the BAT arm on a 2:1 ratio, to receive asciminib treatment (continuous 40 mg BID) or BAT from Day 1 until the end of study treatment period defined as 96 weeks after the last participant receives the first dose.

Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors

A Randomized, Open-label, Multi-center, Phase II Study of Asciminib Versus Best Available Therapy in Chinese Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors

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

Evaluate the major molecular response rate at 24 weeks in asciminib arm

Evaluate the cytogenetic response rate (Complete, Partial, Major, Minor, Minimal, no response) at and by all scheduled data collection time points including 24, 48 and 96 weeks for both asciminib arm and best available treatment arm.

Evaluate the major molecular response rate at week 24 of best available treatment arm, and compare with asciminib arm

Evaluate the major molecular response rate, collected at all scheduled data collection time point (except week 24)

Evaluate the major molecular rate by all scheduled data collection time points including 24, 48 and 96 weeks by treatment group

Evaluate the time from the date of the first dose of study drug to the date of the first documented MMR by treatment group

First document major molecular response to loss of MMR up to 96 weeks after last participant receive the first dose

To evaluate the time from the date of randomization to the date of death (including the survival follow-up period)

Evaluate the time from the date of randomization to the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause (including progressions and deaths observed during the survival follow-up period)

Characterize PK of asciminib in the Chinese CML-CP population. Cmax is the maximum (peak) observed plasma drug concentration after dose administration (ng/mL).

Characterize PK of asciminib in the Chinese CML-CP population. Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (hr).

Characterize PK of asciminib in the Chinese CML-CP population. Trough plasma concentrations (Ctrough)

Characterize PK of asciminib in the Chinese CML-CP population. The partial area under the plasma concentration-time curve from dose time to tau (ng\*hr/mL). For a bid regimen, Tau=12h.

Characterize PK of asciminib in the Chinese CML-CP population. AUClast is the The AUC from the time of dosing to the time of the last measurable plasma concentration (Tlast) (ng\*hr/mL)

Blast Crisis

Antineoplastic Agents

Gastrointestinal Agents

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Nilotinib

Dasatinib

Imatinib Mesylate

Lactitol

Niacinamide

Niacin

Nicotinic Acids

Folic Acid

Vitamin B Complex

Trace Elements

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

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

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

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

Immune System Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Philadelphia Chromosome

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Translocation, Genetic

Chromosome Aberrations

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Anti-Inflammatory Agents

Blinatumomab

Prednisone

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

- Dose escalation will occur conventional Fibonocci 3+3 dose escalation scheme to determine a recommended phase 2 dose (RP2D)

* Dasatinib-Fixed doses oral once a day per cycle
* ABL001 is administered orally daily per cycle
* Prednisone-Fixed doses oral once a day per cycle.

  --- Prednisone will be tapered and stop during cycle 2.
* Blinatumomab - intravenous continuous infusion beginning no earlier than cycle 2 day 1
* Blinatumomab - Day 1-28 of each 42-day cycle, cycles 2-6, total of 5 cycles

•ABL001 is administered daily per 28 day cycle

ABL001

Fixed doses oral once a day per 28 day cycle

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs	NCT03106779	Chronic Myeloge...	Asciminib Bosutinib	18 Years -	Novartis
Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors	NCT04795427	Leukemia, Chron...	asciminib best available ...	18 Years -	Novartis
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
ABL001 + Dasatinib + Prednisone + Blinatumomab in BCR-ABL+ B-ALL or CML	NCT03595917	B-cell Acute Ly... Chronic Myeloid... Philadelphia Ch...	ABL001 Dasatinib Prednisone Blinatumomab	18 Years -	Dana-Farber Cancer Institute
Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation	NCT04666259	Chronic Myeloge...	ABL001	18 Years -	Novartis
Clinical Study of Asciminib in Previously Treated Indian Patients With Ph+ CML-CP Without T315I Mutation and in Patients With Ph+ CML-CP With T315I Mutation	NCT06427811	Philadelphia Ch...	Asciminib	18 Years -	Novartis
Managed Access Programs for ABL001, Asciminib	NCT04360005	Chronic Myeloid...	Asciminib	18 Years - 99 Years	Novartis
Asciminib Roll-over Study	NCT04877522	Chronic Myeloge... Leukemia, Myelo...	Asciminib singl... Asciminib Imatinib Nilotinib Bosutinib Dasatinib	18 Years -	Novartis
A Phase I Study of Oral Asciminib (ABL001) in Patients With CML or Ph+ ALL	NCT02081378	Chronic Myeloge... Philadelphia Ch...	Asciminib (ABL0... Nilotinib Imatinib Dasatinib	18 Years -	Novartis
Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs	NCT03106779	Chronic Myeloge...	Asciminib Bosutinib	18 Years -	Novartis

Spots Global Cancer Trial Database for abl001

Every month we try and update this database with for abl001 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for abl001

Every month we try and update this database with for abl001 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for abl001 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.