Official Title
Managed Access Program (MAP) Cohort Treatment Plan CABL001A02401M to Provide Access to Asciminib for Patients With CML in Chronic Phase (CP) Without Documented T315I Mutation After Failure to or Intolerance of Two Prior TKI OR Patients in CML-CP With Documented T315I Mutation and Without Comparable or Satisfactory Alternative Therapy to Treat the Disease
Brief Summary

This program provides access to asciminib for patients with CML in chronic phase (CP) without documented T315I mutation after failure to or intolerance of two prior TKI OR patients in CML-CP with documented T315I mutation and without comparable or satisfactory alternative therapy to treat the disease

Chronic Myeloid Leukemia

Drug: Asciminib

Asciminib 20 or 40 mg strength tablets will be administered orally twice-daily, without food

Eligibility Criteria

Inclusion Criteria:

- Male or female patients ≥ 18 years of age

- Patients with CML in chronic phase who additionally meet one of the following

1. Patient with absence of T315I mutation, who were previously treated with at least
two prior TKIs and are relapsed, refractory to or intolerant of TKIs as
determined by the treating physician or

2. Patient with presence of T315I mutation who are failing or intolerant to all
available treatments or for whom available treatments are contraindicated

- Patient is deemed by the treating physician to have the initiative and means to be
compliant with treatment and follow-up requested

- Adequate end organ function, within 14 days before the first dose of asciminib
treatment. Patients with mild to severe renal and hepatic impairment are eligible:

- Total bilirubin ≤ 3.0 x ULN AST/ALT any

- Aspartate transaminase (AST) ≤ 5.0 x ULN

- Alanine transaminase (ALT) ≤ 5.0 x ULN

- Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value should be
considered not clinically significant and not associated with risk factors for acute

- Alkaline phosphatase ≤ 2.5 x ULN

- Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft-Gault formula

Exclusion Criteria:

1. History of hypersensitivity to any drugs or metabolites of similar chemical classes as
the product

2. Platelets ≤ 50 x 10^9/L; transient prior therapy related thrombocytopenia (< 50 x
10^9/L for ≤ 30 days prior to asciminib treatment start) is acceptable

3. Active uncontrolled cardiovascular conditions, including ongoing cardiac arrhythmias,
congestive heart failure, angina, myocardial infarction within the past 3-6 months

4. A current 12-lead ECG showing signs of QTcF prolongation

5. A history of active long QT syndrome or risk of Torsades de pointes (TdP) and risk
factors for TdP, such as uncorrected hypokalemia or hypomagnesemia (patient can be
corrected before start of asciminib treatment), any cardiac repolarization abnormality
or Co-administration of any QT prolonging agents.

6. A history of uncontrolled acute pancreatitis within 1 year prior to treatment start,
or chronic active pancreatitis

7. Acute or chronic active non-infectious liver disease

8. Active uncontrolled infection, including pneumonia, requiring systemic therapy or
other severe infections

9. Patients with active HBV and HCV infection, and/or with HCV/HBV viral load above the
limit of quantification after completing curative/suppressive antiviral treatment.

10. Patients with HIV infection with CD4+ T-cell count ≤ 350 cells/uL, and/or patients who
are using concurrent strong CYP3A4 inhibitors (e.g. ritonavir, cobicistat), and cannot
be switched to an alternate effective ART regimen before starting asciminib.

11. Significant other uncontrolled medical conditions, such as (but not limited to)
uncontrolled diabetes, pulmonary hypertension

12. Participation in a prior investigational study within 30 days prior to enrollment or
within 5 half-lives of the investigational product, whichever is longer

13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (> 5 mIU/mL)

14. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, UNLESS they are:

- Women whose sexual orientation precludes intercourse with a male partner

- Women whose partners have been sterilized by vasectomy or other means

- Using a highly effective method of birth control (i.e. one that results in a less
than 1% per year failure rate when used consistently and correctly, such as
implants, injectables, combined oral contraceptives, and some intrauterine
devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal,
post-ovulation methods) is not acceptable Reliable contraception should be
maintained throughout the period of treatment and for 14 days after treatment

Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous
amenorrhea with serum FSH levels > 40 mIU/mL or have had surgical bilateral
oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of
oophorectomy alone, only when the reproductive status of the woman has been confirmed
by follow up hormone level assessment is she considered not of child bearing

15. For US: Sexually active males must use a condom during intercourse while taking the
drug, and for 3 days after stopping treatment and should not father a child in this
period. This applies to men who are vasectomized and men with male partners in order
to prevent delivery of the drug via semen.

16. Not able to understand and to comply with treatment instructions and requirements.

17. Treatment with medications that belong to the below classes and that cannot be
discontinued at least one week prior to the start of treatment

- Strong inducers of CYP3A

- Strong inhibitors of CYP3A

Eligibility Gender
Eligibility Age
Minimum: 18 Years ~ Maximum: 99 Years

MAP requests are initiated by a licensed physician.https:// www.novart

Novartis Pharmaceuticals

Novartis Pharmaceuticals, Study Director
Novartis Pharmaceuticals

Novartis Pharmaceuticals
NCT Number
chronic myeloid leukemia
T315I mutation
MeSH Terms
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive