Monte Rosa Therapeutics Inc (NASDAQ: GLUE) shares declined 4.8% on Monday after the company initiated a Phase 2 clinical trial of its experimental drug MRT-2359 in combination with apalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring androgen receptor (AR) mutations.
The MODeFIRe-1 study has dosed its first patient and aims to enroll up to 25 participants under a Simon’s two-stage design. Eligible patients must have prior exposure to a second-generation AR inhibitor, measurable disease per RECIST criteria, or elevated PSA levels. Primary endpoints include PSA response, radiographic progression-free survival, and safety, with secondary measures covering duration of response and disease control.
MRT-2359, an orally bioavailable GSPT1-directed molecular glue degrader, will be administered at 0.5 mg on a 21-day-on, 7-day-off schedule within 28-day cycles. The trial follows promising data from a prior Phase 1/2 study, where all five AR-mutant patients treated with MRT-2359 plus enzalutamide achieved PSA responses, a 100% disease control rate, and two RECIST-confirmed responses. An expansion cohort of six AR-mutant patients has completed enrollment, with Monte Rosa planning an update on this subset by year-end.
The biotech’s stock reaction reflects investor caution typical for early-stage clinical progress, though the mechanistic rationale and preliminary efficacy signals provide support for the program’s advancement.
