Monte Rosa Therapeutics said the first patient has been dosed in MODeFIRe-1, a Phase 2 study of investigational MRT-2359 combined with apalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) carrying androgen receptor (AR) mutations. The company’s shares fell 4.8% Monday after the announcement. The study will administer 0.5 milligrams of MRT-2359 orally on a 21-days-on, seven-days-off schedule in 28-day cycles and enroll up to 25 patients under a Simon’s two-stage design. Its endpoints include PSA and RECIST responses, duration of response, radiographic progression-free survival (rPFS), PSA progression-free survival and safety. The trial follows early data from a Phase 1/2 study combining MRT-2359 with enzalutamide in heavily pretreated advanced CRPC. All five patients with AR mutations in that group showed a PSA response, with a 100% disease-control rate and two RECIST responses. Enrollment in the expansion arm has been completed, with six AR-mutated patients treated, and Monte Rosa plans to provide updated data by the end of the year. MRT-2359 is an oral, investigational GSPT1-directed molecular glue degrader, a small molecule designed to selectively eliminate a target protein. Monte Rosa said positive further data could support advancement into registrational development, subject to discussions with regulatory authorities, and potentially broaden testing to AR-driven patients without prior second-generation AR inhibitors and to combinations with radioligand therapies regardless of AR status.