Castration-Resistant Prostate Cancer, Castration-Resistant Prostate Cancer (CRPC), Prostate Cancer, Prostate Cancer (Adenocarcinoma)
Conditions
Keywords
MRT-2359, apalutamide, castration-resistant prostate cancer, CRPC, androgen receptor mutation, AR mutation, PSA response, androgen receptor inhibitor, molecular glue degrader, GSPT1
Brief summary
This Phase 2, open-label, multicenter study is conducted in patients with castration-resistant prostate cancer. Patients in this study receive MRT-2359, an investigational oral medicine, in combination with apalutamide, an oral medicine used to treat prostate cancer. The main purpose of the study is to assess whether this treatment combination can lower prostate-specific antigen (PSA) The study will also evaluate the safety and tolerability of the treatment combination and assess additional measures of anti-tumor activity.
Detailed description
This Phase 2, open-label, multicenter study is designed to assess the efficacy, safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of MRT-2359 in combination with apalutamide in patients with castration-resistant prostate cancer. The primary aim of the study is to assess the PSA response rate of MRT-2359 in combination with apalutamide as determined by PCWG4 criteria. Secondary aims include further evaluation of safety and tolerability, additional measures of anti-tumor activity, and characterization of the PK profile of MRT-2359 in combination with apalutamide.
Interventions
DRUGOral MRT-2359
Orally administered tablets of MRT-2359
DRUGApalutamide
Orally administered apalutamide
Sponsors
Monte Rosa Therapeutics, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single group assignment, all participants will receive MRT-2359 in combination with apalutamide.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the efficacy of MRT-2359 combined with apalutamide | 14 months | Assess the efficacy of MRT-2359 combined with apalutamide using the PSA response rate as determined by PCWG4 criteria in participants with measurable and/or evaluable disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Further evaluation of the safety and tolerability of MRT-2359 administered orally in combination with apalutamide | 20 months | Further evaluate the safety and tolerability of MRT-2359 administered orally in combination with apalutamide over a 28-day cycle by the nature, incidence, and severity of all adverse events |
| To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide | 20 months | Objective response rate as determined by RECIST 1.1 |
| To characterize the population pharmacokinetic profile of MRT-2359 in combination with apalutamide | 20 months | Peak Plasma Concentration (Cmax) |
Countries
United States
Contacts
CONTACTMonte Rosa Therapeutics Sponsor
Outcome results
None listed