Individual Patient Expanded Access for Velzatinib (GSK6042981) in Patients With Gastrointestinal Stromal Tumours With KIT Mutations

Specific eligibility criteria must be met for access outside of a clinical trial. These include:

1. There is no satisfactory alternative treatment for the patient including approved standard of care treatments for their diagnosis of Gastrointestinal Stromal Tumour (GIST)
2. There is reason to believe that the benefit of the patient using GSK6042981 (IDRX-42) outweighs the risk
3. Patient does not qualify for other ongoing clinical trials

Additional inclusion and exclusion criteria are detailed below.

Inclusion Criteria:

Patients are eligible to be included in the Programme only if all the following criteria apply:

1. Patient is diagnosed with Gastrointestinal Stromal Tumour (GIST) and positive for a KIT mutation (in one of exons 9, 11, 13, 17)
2. Patient has had at least 3 prior lines of therapy
3. Patient has adequate organ system function
4. Written informed consent can be obtained from the patient or legally authorized representative
5. Patient is 18 years or older
6. Required Contraception
7. Female participants of childbearing potential, if not postmenopausal or surgically sterile, must agree to abstain from heterosexual intercourse or use a highly effective form of contraception with their sexual partners during the dosing period and for a period of at least 30 days after the end of treatment.

Male participants with partners of childbearing potential must agree that they will abstain from heterosexual intercourse or use condoms and their partners will use highly effective contraceptive methods during the dosing period until at least 30 days after the last dose of study drug

Exclusion Criteria:

Patients are excluded from the Programme if any of the following criteria apply:

1. Active uncontrolled infection
2. Known hypersensitivity to GSK6042981 or any of the formulation excipients
3. Women who are pregnant or currently breastfeeding
4. ALT >2.5xULN or (for patients with documented liver metastases/tumour infiltration) has an ALT value >5xULN
5. Total bilirubin >1.5xULN; patients with Gilbert's syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is ≤1.5xULN.
6. Cirrhosis or current unstable liver or biliary disease per physician assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if patient otherwise meets entry criteria).

7. Patients with Hepatitis B will be excluded unless the following conditions are met: for patients who are hepatitis B core antibody positive and hepatitis B surface antigen negative (HbcAb+, HBsAg-), HBV DNA must be undetectable at screening and the patient must be monitored according to standard of care during programme treatment, with antiviral therapy instituted if HBV DNA becomes detectable. For patients who are hepatitis B surface antigen positive (HBsAg+) at screening or within 3 months prior to the first dose of programme treatment, HBV DNA must be undetectable at screening, highly effective antiviral treatment must be initiated at least 4 weeks prior to the first dose of programme treatment and maintained throughout programme treatment, and the patient must be monitored and managed according to standard of care.

   Note: Presence of isolated Hep B surface antibody (HBsAb) indicating previous vaccination will not exclude a patient

8. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of programme treatment unless the patient can meet the following criteria:

   1. RNA test negative
   2. Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks.