• Patients with unresectable or metastatic melanoma with an NF1 mutation; Variance of NF1 of unknown/ uncertain significance will not be eligible; The genetic analysis for somatic mutations must be performed in a lab that has obtained CLIA certification.

• Patients must have a report of NF1 sequencing analysis performed at CLIA-certified laboratory (by either tissue-based sequencing or liquid biopsy)

• Must have been previously treated with

‣ anti PD-1/PD-L1 antibody; AND anti CTLA-4 antibody and/or anti LAG3 antibody;

⁃ UNLESS these standard checkpoint inhibitors are not clinically indicated or suitable (for example, comorbid conditions, such as autoimmune disease, or significant toxicity with prior checkpoint inhibitor treatment)

• Tumors must be progressing at the time of the enrollment

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

• Patients must be ≥ 18 years of age

• Patients must have measurable metastatic disease according to RECIST 1.1

• Patients must have adequate organ function, defined as follows:

• Absolute neutrophil count ≥ 1,500/μL

• Platelets ≥ 100,000/μL

• Hemoglobin ≥ 9 g/dL

• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Grade ≤1). • Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)

• Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN (Grade ≤1) unless liver metastases are present, in which case they must be ≤ 5 x ULN (Grade ≤2).

• Adequate coagulation function, as determined by:

• International Normalized Ratio (INR) ≤ 1.5 × ULN (Grade ≤ 1). If the participant receives anticoagulant therapy, the INR \> 1.5 × ULN is permitted, but the dose must be stable for at least 2 weeks before the start of the study treatments.

• PTT ≤ 1.5 × ULN.

• Adequate cardiac function, as determined by:

• Systolic blood pressure \< 160 mmHg and diastolic blood pressure \< 100 mmHg (Grade ≤ 2).

• LVEF ≥ 50% by MUGA or ECHO.

• No clinically significant ECG waveform abnormalities assessments at screening (one triplicate).

• Have normal serum calcium and phosphate levels (calcium level may be corrected for albumin level).

• Female patients are eligible to enroll and participate in the study if:

• Patient is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:

∙ has had a hysterectomy.

‣ has had a bilateral oophorectomy (ovariectomy).

‣ has had bilateral tubal ligation.

‣ is postmenopausal (total cessation of menses for ≥1 year), OR

• Women of child-bearing potential must agree to use highly effective contraceptive methods (hormonal or barrier method of birth control or abstinence) during the trial period through at least six months after the last dose. Male patients or their partners must be surgically sterile or agree to use adequate contraception while receiving trial treatment and for three months thereafter. Contraceptive use by men or women should be consistent with Clinical Trials Coordination Group (CTCG) guidance.

• Patients must be able to understand the study procedures and agree to participate in the study by providing written informed consent.