Advanced Physician Search: 3rd Line and Beyond

This phase II trial compares the effect of giving cabozantinib with or without cemiplimab in patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), and that cannot be removed by surgery (unresectable) or that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib with cemiplimab may kill more tumor cells in patients with locally advanced unresectable or recurrent/metastatic adrenocortical cancer.

Procedure: Biospecimen Collection, Drug: Cabozantinib, Biological: Cemiplimab, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging

This is a two-stage Phase 2 trial evaluating the efficacy and safety of ONC206 in participants with Pheochromocytoma and Paraganglioma (PCPG).

Drug: ONC206: Dose 2

The investigators hypothesize that zanzalintinib maintenance therapy after initial cytotoxic chemotherapy can prolong the progression-free survival (PFS) in patients with high-grade NENs.

Drug: Zanzalintinib

This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of RYZ101 compared with investigator-selected standard of care (SoC) therapy in Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following treatment with Lutetium 177-labelled somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or 177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity [HA]-DOTATATE.

Drug: RYZ101

This study is Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Tumors

Drug: [203Pb]VMT-α-NET, Drug: [212Pb]VMT-α-NET