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

• Other Inclusion Criteria:

1. In the opinion of the treating physician, the patient has exhausted or hasinadequate response to available anti-cancer treatments.

2. In the opinion of the treating physician, the patient has adequate organfunction 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 patientswith any prior stomach or duodenal resection should be evaluated with thatunderstanding.

5. For females, evidence of post-menopausal status or negative urinary or serumpregnancy test for pre-menopausal patients.

6. Highly effective contraception for both male and female patients throughout thetreatment and for at least 4 months after last treatment administration. Inpatients under the age of 18, who are not sexually active, abstinence is anacceptable form.

7. Toxicities related to any prior treatments are either stable, stable onsupportive therapy, resolved, or in the opinion of the treating physician,clinically non-significant

8. Ability to understand a written informed consent document, and the willingnessto sign it. Assent will be obtained when appropriate based on the patient'sage.

Exclusion Criteria:

1. Patient is already participating in or qualifies for and is able to enroll in aclinical trial of ulixertinib (BVD-523).

2. Patient has received systemic therapy with an investigational agent within 5half-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 ofulixertinib treatment other than for the allowable treatment of symptomatic bonemetastasis.

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

5. Current evidence of uncontrolled, significant intercurrent illness that would, inthe treating physician's judgment, contraindicate the patient's treatment withulixertinib due to safety concerns.

6. Patients who, in the opinion of the treating physician, have not fully recoveredfrom recent major surgery to a sufficient extent to tolerate treatment withulixertinib.

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

8. Patients taking prohibited medications as described in current Investigator'sBrochure. Note: Patients who require treatment with Drugs that are strong inhibitors orinducers of CYP1A2, CYP2D6, and CYP3A4 (see Appendix 3) were excluded from the FIHstudy of ulixertinib and should be discussed with xCures to review if any potentialbenefits outweigh the potential risks.

9. Patient is actively breastfeeding.

10. Prior stomach or duodenal resection that in the opinion of the treating physicianwould affect the breakdown and absorption of ulixertinib.