Rigosertib Plus Pembrolizumab in Treating Patients With Unresectable/Metastatic Melanoma Refractory to PD-1 Inhibitors (NCT05764395)

Usually NOT eligible if any of the following apply:

• Exclusion Criteria:
• Has a diagnosis of primary uveal or mucosal melanoma.
• A WOCBP who has a positive urine pregnancy test within 72 hours of the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication. Pregnancy testing will be obtained every three months while on study treatment; patients will be withdrawn from the study if pregnancy occurs.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (for immunotherapeutic agents) or within 2 weeks (for targeted therapeutics) prior to the first dose of study drug. If a subject has experienced adverse events (AE) from prior treatment, he/she must have recovered from all AEs to \< grade 1 or baseline. Patients with \< grade 2 neuropathy may be eligible. Patients with endocrine-related AEs \< 2 requiring treatment or physiologic steroid replacement may be eligible.
• Has received prior radiotherapy within 2 weeks of the first dose of study drug. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• If participant has had recent major surgery, the participant must has recovered adequately from the procedure and/or any complications from the surgery prior to the first dose of study drug.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with non-melanoma skin cancer (eg, basal cell carcinoma of the skin, squamous cell carcinoma of the skin) or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Subjects with untreated active central nervous system (CNS) metastases, active brain metastases or leptomeningeal metastatic foci. For the subjects with brain metastases, if they have received treatment and have no evidence of progressive disease on magnetic resonance imaging (MRI) at least 4 weeks after completion of the treatment and within 30 days prior to the first dose, they are eligible to participate in the study.
• Has a history of severe hypersensitivity (\>= grade 3), specifically infusion reaction or anaphylaxis to pembrolizumab and/or any of its excipients.