Study of Oral MRT-2359 With Apalutamide in Prostate Cancer

Inclusion Criteria:

* Age \> 18 years
* A predicted life expectancy of ≥ 3 months and an ECOG performance status ≤ 1
* Have histologically or cytologically confirmed castration-resistant adenocarcinoma of the prostate without small cell histology and with androgen receptor (AR) mutations
* Have not had prior treatment with more than 1 prior taxane-based chemotherapy regimen for castration-resistant prostate cancer
* Have no prior treatment with an AR degrader, opevesostat, or similar therapy
* Has ongoing (chemical or surgical) androgen deprivation with serum testosterone \< 50 ng/dL (\< 1.7 nM)
* Has received prior treatment with poly(ADP-ribose) polymerase (PARP) inhibitor, if appropriate, or deemed ineligible to receive treatment by the Investigator, or has refused PARP inhibitor treatment
* Has received prior treatment with at least 1 line of ARPi
* Have disease measurable per Prostate Cancer Working Group 4 (PCWG4) criteria, with or without measurable disease by RECIST 1.1
* Be able to provide a tumor biopsy for biomarker analysis during the Screening period
* Have adequate organ function

Exclusion Criteria:

* • Have received prior chemotherapy, definitive radiation, or biological cancer therapy within 21 days before the first dose of study treatment or have any AEs that have failed to recover to baseline

  * Have received prior therapy with a GSPT1 degrader that was discontinued due to an AE
  * Have received prior auto-HCT and have not fully recovered from effects of the last transplant
  * Have received allogeneic hematopoietic stem cell transplantation within past 6 months and/or have symptoms of graft-versus-host disease
  * Current use of chronic systemic steroid therapy in excess of replacement doses
  * Have clinically active central nervous system involvement and/or carcinomatous meningitis
  * Have a confirmed history of (noninfectious) pneumonitis that required steroids
  * Clinically significant cardiac disease