Phase IIIa Study of AZD3470 Alone and with Datopotamab Deruxtecan in Adults with MTAP Deficient Advanced or Metastatic Solid Tumors

What this Trial Is About

Researchers are studying AZD3470, a new drug that inhibits PRMT5, in adults with advanced or metastatic solid tumors that lack the MTAP gene. This first-in-human Phase IIIa trial aims to evaluate the safety, tolerability, how the drug moves and acts in the body, and early signs of effectiveness. The study includes several parts to test AZD3470 alone or combined with other cancer drugs like Datopotamab deruxtecan Dato-DXd. New combination treatments may be added based on ongoing results. Participants will join different modules where they receive varying doses of AZD3470 alone or with Dato-DXd, or Dato-DXd alone as a control. The study starts with dose escalation and optimization phases to find the best dose. Later phases focus on evaluating AZD3470 combined with Dato-DXd versus Dato-DXd alone for efficacy and safety. Treatments are given in cycles of 21 days, and the study design allows for sequential evaluation across modules. Throughout the study, participants will undergo regular safety monitoring including adverse event tracking, laboratory tests, and imaging scans assessed by RECIST criteria. Pharmacokinetic and pharmacodynamic assessments will measure how AZD3470 behaves in the body. Researchers will also evaluate progression-free survival, tumor response, duration of response, and overall survival. Follow-up may continue up to two years after treatment to assess long-term effects and disease control.

A Study of AZD3470, a PRMT5 Inhibitor, Given as Monotherapy and in Combination in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors