Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies.

Inclusion Criteria

- Main Inclusion Criterion:

1. Patient has a MAPK pathway-altered solid tumor(s), including but not limited to

KRAS, NRAS, HRAS, BRAF, MEK, and ERK mutations.

- Other Inclusion Criteria:

1. In the opinion of the treating physician, the patient has exhausted or has

inadequate response to available anti-cancer treatments.

2. In the opinion of the treating physician, the patient has adequate organ function

to tolerate ulixertinib as defined in section 6.1

3. Male or female patients aged ≥ 12 years.

4. Patient must be able to swallow and retain orally administered medication.

Note: Ulixertinib is primarily absorbed in the duodenum and therefore patients

with any prior stomach or duodenal resection should be evaluated with that

understanding.

5. For females, evidence of post-menopausal status or negative urinary or serum

pregnancy test for pre-menopausal patients.

6. Highly effective contraception for both male and female patients throughout the

treatment and for at least 4 months after last treatment administration. In

patients under the age of 18, who are not sexually active, abstinence is an

acceptable form.

7. Toxicities related to any prior treatments are either stable, stable on

supportive therapy, resolved, or in the opinion of the treating physician,

clinically non-significant

8. Ability to understand a written informed consent document, and the willingness to

sign it. Assent will be obtained when appropriate based on the patient's age.

Exclusion Criteria

1. Patient is already participating in or qualifies for and is able to enroll in a

clinical trial of ulixertinib (BVD-523).

2. Patient has received systemic therapy with an investigational agent within 5

half-lives or 14 days prior to starting ulixertinib treatment, whichever is shorter.

3. Patient has received radiotherapy within 14 days prior to the first dose of

ulixertinib treatment other than for the allowable treatment of symptomatic bone

metastasis.

4. A history of current evidence/risk of retinal vein occlusion (RVO) or central serous

retinopathy (CSR)

5. Current evidence of uncontrolled, significant intercurrent illness that would, in the

treating physician's judgment, contraindicate the patient's treatment with ulixertinib

due to safety concerns.

6. Patients who, in the opinion of the treating physician, have not fully recovered from

recent major surgery to a sufficient extent to tolerate treatment with ulixertinib.

7. Known hypersensitivity to ulixertinib or any component in its formulation.

8. Patients taking prohibited medications as described in current Investigator's

Brochure.

Note: Patients who require treatment with Drugs that are strong inhibitors or inducers

of CYP1A2, CYP2D6, and CYP3A4 (see Appendix 3) were excluded from the FIH study of

ulixertinib and should be discussed with xCures to review if any potential benefits

outweigh the potential risks.

9. Patient is actively breastfeeding.

10. Prior stomach or duodenal resection that in the opinion of the treating physician

would affect the breakdown and absorption of ulixertinib.