This study explores a new treatment using an anti-cancer drug called DT2216 with the usual chemotherapy, irinotecan, for kids and young adults with tough-to-treat cancers. DT2216 works by stopping a protein that cancer cells need to survive. Irinotecan is a medication that helps stop cancer cells from growing by blocking a specific enzyme. The study is divided into two parts: Phase I checks the safest and best dose, while Phase II looks at how well the treatment works. Participants receive DT2216 and irinotecan through IV (intravenously) on specific days every 21 days, and this can go on for up to 2 years.

• Study involves frequent hospital visits for IV treatment every 21 days, potentially lasting up to 2 years.
• Participants are monitored closely for safety and side effects throughout the study.
• Eligible ages are 1-21 for Phase I and 1-39 for Phase II.

After finishing treatment, follow-up visits continue for several years. This study aims to find out if combining DT2216 with irinotecan is safe and effective, but there may be side effects since it is in early trial phases.