This research is being done to better understand how anti-cancer drugs affect cells within a tumor. Injecting very small amounts (microdoses) of pembrolizumab alone or in combination with MK-0482 or MK-4830 above may help the developer of these drugs to understand more about how these drugs work and what changes they make on the tumor. Subjects in this study will have their tumor injected with anti-cancer drugs using a CIVO device. The CIVO device delivers microdoses of multiple drugs or drug combinations directly into the tumor. Some of the procedures in this study include ultrasound assisted placement for tumor injection, a mucrodose injection of anti-cancer drugs into the tumor, and surgery to remove the tumor. Participation in the study will take 5 visits over a period if 56 days. The screening portion will be 28 days and the treatment portion will be 28 days from the time of the injection to the time of follow-up contact by the study team.

The purpose of this study is to assess the feasibility and safety of modified surgical eyeglasses to view bevonescein intraoperatively and the safety of bevonescein as it shows nerve tissue in the body. Bevonescein is an investigational drug being developed to help doctors identify nerves within the body during surgery.
The drug is administered through a vein in the arm and into the blood stream.t Bevonescein then travels through the blood where it makes nerve tissue fluorescent so that it can then be detected by the modified surgical eyeglasses used in this study by a surgeon. This may help the surgeon (study doctor) to tell the difference between nerve tissue and other tissue during surgery. Bevonescein and the modified surgical eyeglasses that your surgeon will wear (ReVealTM 475) are considered investigational because they are not approved by the Food and Drug Administration (FDA) to help with the visualization of nerves during surgery Alternatives to this study can include to undergo surgery without the study drug.

The duration of this study is about 2 months. The procedures of this study include administration of the study drug once (500 mg), collection of blood and urine samples, and ECGs. Surgery will happened as planned by the study doctor but as part of the research, the surgeon will ear modified surgical eyeglasses to view nerves and may take pictures or video clips. The glasses are FDA cleared but the modified filter and its use in combination with bevonescein is considered experimental.

The most commonly expected risks of fluorescein are nausea, vomiting, and stomach discomfort. Because bevonescein is cleared through the urine, there may be a potential risk to the kidneys and renal (kidney) system. The most serious risks of fluorescein may include severe local tissue damage, anaphylaxis, convulsions, cardiac arrest, and death.

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.