Castration-Resistant Prostate Cancer (CRPC)Phase 2MODeFIRe-1NCT07745361
Study of Oral MRT-2359 With Apalutamide in Prostate Cancer
A Phase 2 study testing Oral MRT-2359 and Apalutamide in people with Castration-Resistant Prostate Cancer (CRPC) and Castration-Resistant Prostate Cancer, run by Monte Rosa Therapeutics, Inc at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Castration-Resistant Prostate Cancer (CRPC), Castration-Resistant Prostate Cancer, Prostate Cancer
- What is being tested?
- Oral MRT-2359 and Apalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 14 sitesUnited States
- Study dates
- 18 Aug 2026to Apr 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- • 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
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
14 sites in 1 country
United States14 sites, 14 recruiting
- Not yet recruiting
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
- Not yet recruiting
Levine Cancer Institute
Charlotte, North Carolina, 28204
- Not yet recruiting
Rocky Mountain Cancer Center
Colorado Springs, Colorado, 80907
- Recruiting
START New Jersey
East Brunswick, New Jersey, 08816
- Not yet recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
- Not yet recruiting
Kansas University Cancer Center
Kansas City, Kansas, 66160
- Not yet recruiting
Lancaster Urology
Lancaster, Pennsylvania, 17601
- Recruiting
START Los Angeles
Los Angeles, California, 90025
- Not yet recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
- Not yet recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
- Not yet recruiting
Henry Ford
Novi, Michigan, 48377
- Recruiting
XCancer Omaha
Omaha, Nebraska, 68130
- Recruiting
University of Washington Medical Center
Seattle, Washington, 98195
- Recruiting
START Mountain Region
West Valley City, Utah, 84119
About this study
Official title: MODeFIRe-1 (Molecular Degrader for Inhibitor Resistance): A Phase 2, Open-Label, Multicenter Study of Oral MRT-2359 in Combination With Apalutamide in Patients With Castration-Resistant Prostate Cancer
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.
Read the 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.
- Conditions
- Castration-Resistant Prostate Cancer (CRPC), Castration-Resistant Prostate Cancer, Prostate Cancer, Prostate Cancer (Adenocarcinoma)
- Being tested
- Oral MRT-2359, Apalutamide
- Keywords
- MRT-2359, apalutamide, castration-resistant prostate cancer, CRPC, androgen receptor mutation, AR mutation, PSA response, androgen receptor inhibitor, molecular glue degrader, GSPT1
- Medical subject headings
- Prostatic Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral MRT-2359Drug
Orally administered tablets of MRT-2359
ApalutamideDrug
Orally administered apalutamide
| Study group | Role | What they receive |
|---|---|---|
| MRT-2359 + Apalutamide | Experimental | Participants with castration-resistant prostate cancer will receive MRT-2359 in combination with apalutamide. Receives: Drug: Oral MRT-2359; Drug: Apalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the efficacy of MRT-2359 combined with apalutamide
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
Measured: 14 months
Secondary outcomes (11)
Further evaluation of the safety and tolerability of MRT-2359 administered orally in combination with apalutamide
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
Measured: 20 months
To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide
Objective response rate as determined by RECIST 1.1
Measured: 20 months
To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide
Duration of response (DoR) in participants with CR or PR per RECIST 1.1
Measured: 20 months
To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide
Duration of response (DoR) in participants with the best overall response of PSA50 per PCWG4
Measured: 20 months
To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide
Disease control rate (DCR) per RECIST 1.1
Measured: 20 months
To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide
Radiographic progression free survival (PFS)
Measured: 20 months
To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide
PSA progression free survival (PFS)
Measured: 20 months
To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide
Overall survival (OS)
Measured: 20 months
To characterize the population pharmacokinetic profile of MRT-2359 in combination with apalutamide
Peak Plasma Concentration (Cmax)
Measured: 20 months
To characterize the population pharmacokinetic profile of MRT-2359 in combination with apalutamide
Minimum Plasma Concentration (Cmin)
Measured: 20 months
To characterize the population pharmacokinetic profile of MRT-2359 in combination with apalutamide
Area Under the Plasma Concentration-time Curve (AUC)
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2026
- Study start18 Aug 2026
- Primary completionOct 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Castration-Resistant Prostate Cancer (CRPC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group assignment, all participants will receive MRT-2359 in combination with apalutamide.
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monte Rosa Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07745361
- Sponsor's protocol ID
- MRT-2359-002
- Acronym
- MODeFIRe-1
- Status last verified
- Oct 2026
- First submitted
- 29 Jul 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No