On August 24, 2026 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported that the first patient has been dosed in MODeFIRe-1 (clinicaltrials.gov identifier NCT07745361), a Phase 2 study evaluating MRT-2359 in combination with apalutamide, a second-generation androgen receptor (AR) inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) with AR mutations. The study follows encouraging clinical data previously shared from the Company’s Phase 1/2 study of MRT-2359 in combination with enzalutamide in heavily pretreated mCRPC patients. MRT-2359 is an investigational, orally bioavailable, GSPT1-directed MGD discovered and developed by Monte Rosa.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Dosing the first patient in MODeFIRe-1 is an important step in advancing MRT-2359 as a potential therapy for patients with mCRPC with AR mutations, a population with limited therapeutic options," said Filip Janku, M.D., Ph.D., Chief Medical Officer of Monte Rosa Therapeutics. "This study builds on the encouraging results we observed in our Phase 1/2 study of MRT-2359 in combination with enzalutamide. As we disclosed previously, in that study of heavily pretreated, advanced CRPC patients – including those who had progressed on prior second-generation AR inhibitors, chemotherapy, and radioligand therapy – 5 of 5 patients with AR mutations demonstrated a PSA response, with a 100% disease control rate and two RECIST responses. MODeFIRe-1 pairs MRT-2359 with apalutamide using a design intended to efficiently further evaluate and potentially confirm clinical activity in this population. We believe this study can position MRT-2359 for advancement into registrational development if the data continue to support our earlier results, with the potential to also extend clinical benefit to additional AR-driven patient populations including patients without prior second-generation AR inhibitors, as well as into combinations with radioligand therapies independent of AR status."

MODeFIRe-1 will evaluate MRT-2359 at a dose of 0.5 mg administered orally on a 21 days on, 7 days off schedule over 28-day cycles, in combination with apalutamide. The study will enroll up to 25 patients with mCRPC with AR mutations, utilizing a Simon’s two-stage design. Eligible patients must have AR mutations, PSA with or without RECIST-measurable disease, and prior treatment with a second-generation AR inhibitor. Study endpoints include PSA response, RECIST response, duration of response, radiographic progression-free survival (rPFS), PSA progression-free survival, and safety.

Enrollment in the initial Phase 1/2 study expansion arm in patients with advanced CRPC has been completed. A total of 6 patients with AR mutations were enrolled and treated with MRT-2359 in combination with enzalutamide. Monte Rosa plans to provide an update on this patient subset by the end of the year. Interim data were presented at the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in February.

About MRT-2359
MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) of GSPT1. MYC-driven cancers, including prostate cancer, depend on enhanced translation of oncoproteins to support rapid growth. MRT-2359 exploits this therapeutic vulnerability by disrupting translation through selective degradation of the translation termination factor GSPT1. MRT-2359 treatment reduced cellular abundance of many prostate cancer-relevant oncoproteins, including AR, MYC, and Cyclin D1-E2F, and demonstrated robust anti-tumor activity across multiple preclinical models of metastatic castration-resistant prostate cancer (mCRPC). MRT-2359 is being evaluated in combination with apalutamide in MODeFIRe-1, a Phase 2 study in mCRPC patients with AR mutations. In a Phase 1/2 study, the combination of MRT-2359 with the AR inhibitor enzalutamide demonstrated encouraging early signals of clinical response in mCRPC patients with AR mutations.

(Press release, Monte Rosa Therapeutics, AUG 24, 2026, View Source [SID1234670308])