Immuno-Oncology (IO) therapies have revolutionized cancer therapy and are becoming the standard of care for many cancers. Monitoring how well IO therapies work against cancer is difficult due to the complexity of the immune system and the fact that an immune response may initially increase, rather than decrease, the size of a tumor. An early response marker would be beneficial to determine which patients should remain on a given treatment or combination of treatments, and which patients should seek other treatment options. 18F-LY3546117 is a radiolabeled tracer that binds to a specific protein (Granzyme B) that is found in the human immune system and is thought to trigger programmed cell death. It is thought that imaging Granzyme B activity in tumors and elsewhere in the body using a Positron Emission Tomography (PET) scan will allow doctors to monitor the progress of IO therapy.

Inclusion Criteria (Cohort 1):

• At least one imageable tumor greater than or equal to 15 mm in the longest diameter
• Confirmed diagnosis of cancer with a high likelihood of response to immuno-oncology therapy (melanoma or non-small cell lung cancer, or other malignancies with sponsor approval) and planned mono- or combination therapy with immuno-oncology therapy
• Life expectancy of greater than 6 months

Inclusion Criteria (Cohort 2):

• At least one imageable tumor greater than or equal to 15 mm in the longest diameter or a tumor assessable by PET in the opinion of the radiologist
• Received treatment with an immune checkpoint inhibitor with evidence of response
• Life expectancy of greater than 6 months

Exclusion Criteria:

• Subjects who plan to receive chemotherapy or radiation therapy during study participation
• Prior history of failed immune checkpoint inhibitor therapy
• Subjects who require steroid or other immunosuppressive medications within 2 weeks of the PET scan.
• Females of childbearing potential who are not surgically sterile, not refraining from sexual activity, or not using effective methods of contraception. Females of childbearing potential must not be pregnant or breastfeeding at screening and agree to avoid becoming pregnant for 24 hours following study drug administration.
• Females and males must agree to refrain from sexual activity or to use effective contraceptive methods for 24 hours following study drug administration and during study participation