This study investigates how inhibiting a protein called RIPK1 might affect the immune system in patients with pancreatic cancer. RIPK1 is a gene that has been linked to resistance against immunotherapy, a type of cancer treatment that helps the immune system fight cancer. In animal studies, blocking RIPK1 in pancreatic cancer changed the types of immune cells around the tumor, making it easier for the body to attack the cancer. The purpose of this study is to see if similar effects occur in humans and if it can make pancreatic tumors more responsive to treatment.

Participants in this study will undergo procedures that include providing tumor samples through biopsies. A biopsy is a procedure where a small piece of the tumor is removed to be examined. Participants will need to provide a sample before starting the treatment and another one after about five weeks of treatment. These samples will help researchers understand how the treatment affects the tumor and the immune cells around it.

• Who can participate: Adults aged 18 and older with locally advanced or recurrent pancreatic cancer, non-small cell lung cancer, triple negative breast cancer, or melanoma that has not responded to standard treatments may be eligible. Participants should have adequate organ function and must not have had certain prior treatments or health conditions.
• Study details: Participants will receive an investigational medication to test its effects on their cancer. Some may receive a placebo, which is an inactive substance that looks like the investigational medicine but does not contain any medicine. Participants will need to follow specific guidelines regarding contraception and provide biopsies during the study.