This trial is for people with melanoma. This trial is testing the V940 (mRNA-4157) vaccine given in combination with pembrolizumab in people who have surgery to remove their melanoma. The vaccine has multiple patient-specific neoantigens that could improve the recurrence-free survival after the surgery. Each participant will participate in the study for approximately 7 years from the time the participant provides full documented informed consent through the final contact. There is a screening window of up tp 56 days where the participants receives tumor scan, brain scan, pathology report, hematology, coagulation tests, hormones, enzymes, and blood for genetic sequencing and vaccine generation. After a screening period of up to 56 days, each participant will be receiving assigned intervention for a maximum of approximately 56 weeks. The participants will be assigned to the two arms in the study randomly after the genetic testing confirms eligibility based on disease risk and age. Arm A will receive and a V940 injection in the muscle every 3 weeks for a total of 9 doses and pembrolizumab ever 6 weeks for a total of 9 cycles. Arm B will receive Placebo every 3 weeks for 9 dose and pembrolizumab every 6 weeks for 9 cycles. After the end of treatment each participant will be followed for approximately 6 years. V940 monotherapy has been well tolerated, but injection site observations included edema and pain/tenderness, and systemic inflammatory observations, including flu like symptoms, fever, fatigue, and myalgias/arthralgias, all of which have typically resolved 1 to 2 days after dosing). The clinical safety profile of V940 does not significantly overlap with pembrolizumab. Pembrolizumab has a positive benefit-risk profile and is well tolerated. Some possible risks associated with pembrolizumab are fatigue, pruritus , rash , diarrhea, nausea, hypothyroidism, pneumonitis, colitis, pyrexia and autoimmune hepatitis, pneumonia, adrenal insufficiency and hyponatremia.

The purpose of this study is to evaluate investigational treatments (study drug) for locally advanced or metastatic solid tumors with oncogene amplifications to determine if any of these study treatments improve overall survival as compared to standard treatments.

The goal is to determine the optimal dose level, safety, and tolerability for the study drug BBI-355. This is the first study to test the study medicine BBI-355 in humans; BBI-355 is not FDA approved by the U.S. Food and Drug Administration (FDA). Treatment for this study may be up to 3 years. The procedures include taking study drug orally, blood and urine samples, diary entries, and CT scans. Risks include diarrhea, nausea, vomiting, fatigue, muscle weakness, dizziness, and headaches. You may or may not receive a direct benefit from participating in this trial, however, information learned from the trial may help other people in the future.