This study is for adults with pancreatic cancer that has spread, causing weight loss and tiredness. It aims to test how well a new medicine called ponsegromab works when combined with standard cancer treatments. Cachexia means severe weight loss and muscle wasting. Participants will receive either the new medicine or a placebo (a harmless substance with no treatment) alongside their chemotherapy. Systemic chemotherapy means the medicine spreads throughout the body to kill cancer cells. The study is randomized, meaning participants are randomly assigned different treatments, and double-blind, so neither the participants nor the researchers know who gets which treatment. This study will also check how safe and tolerable the new medicine is.

• The study involves regular visits for tumor assessments every 6 to 8 weeks.
• Participation may last until the study ends or if you decide to stop.
• Caregivers can join a sub-study to see if the new medicine helps them, too.