MRT-2359

DEVELOPMENT STEP phase-1

SPONSOR MATRIX Monte Rosa Therapeutics [GLUE]

MECHANISM TARGET // UNMAPPED_TARGET

[THERAPEUTIC_PROFILE]

Target Indications

Castration-resistant Prostate Cancer

Mechanism Abstract

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 androgen receptor (AR), MYC, and Cyclin D1-E2F, and demonstrated robust anti-tumor activity across multiple preclinical models of metastatic castration-resistant prostate cancer (mCRPC). In heavily pretreated mCRPC patients, MRT-2359 in combination with the AR inhibitor enzalutamide has demonstrated encouraging early signals of clinical response.

[3D_INTERACTIVE_CONFORMATION]

PUBCHEM CID: 164584214

INTERACTIVE_3D_CONFORMATION

     INITIALIZING_STRUCTURAL_BIOMATRIX... 

[CLINICAL_TRIALS_REGISTRY]

TOTAL EXTRACTED1

RECRUITING STATUS0

COMPLETED RUNS0

REGISTRY & PHASE

TESTED CONDITION

STUDY TITLE & LIFECYCLE TIMELINES

STATUS

➔

P-1NCT05546268

NSCLCSCLC+6 more

N=174Est. Finish: 2027-11

Study of Oral MRT-2359 in Selected Cancer Patients

active not recruiting

ENROLLMENT PATIENT CAPACITY174 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2022-10-12(actual)

Primary End:2026-05(estimated)

Study Finish:2027-11(estimated)

OFFICIAL PROTOCOL TITLE

A Phase 1/2 Study of Oral MRT-2359 in Patients With MYC-Driven and Other Selected Solid Tumors Including Lung Cancer and Diffuse B-Cell Lymphoma

[INVESTIGATORS_&_FACILITY_ROSTER]

// NO_EXPLICIT_INVESTIGATORS_OR_ROSTERS_LOGGED

[PRIMARY_SUCCESS_ENDPOINTS]

Phase 1 Evaluates safety and tolerability of MRT-2359 over a 28-day cycle by the occurrence and frequency of dose limiting toxicities (DLTs) for determination of the MTD and/or RP2D

Analysis Window: 28 days

Phase 2 Evaluates preliminary anti-tumor activity of MRT-2359 by overall response rate (ORR) as determined by RECIST 1.1

Analysis Window: 56 days (up to approximately 24 months from screening to end of study participation

[SECONDARY_SUCCESS_ENDPOINTS]

Phase 1 safety and tolerability of MRT-2359 (orally over a 28-day cycle) by the nature, incidence, and severity of all treatment-emergent adverse events (TEAEs), including treatment-related TEAEs and serious adverse events (SAEs)

Analysis Window: 18 months

Phase 1 preliminary anti-tumor activity: ORR (RECIST 1.1/Revised Response Criteria for Malignant Lymphoma),duration of response for complete response(CR)/partial response(PR), disease control rate, progression-free survival, overall survival

Analysis Window: 18 months

Phase 1 Dose Escalation characterizes the PK profile of MRT-2359 by standard primary PK parameters including, but not limited to, AUC, Cmax, tmax, and t1/2

Analysis Window: 28 days

Phase 1 Dose Escalation evaluates the effect of a high-fat meal on the relative bioavailability of MRT-2359 by standard primary PK parameters including, but not limited to, AUC and Cmax

Analysis Window: 7 days

Phase 2 Dose Expansion evaluates the safety and tolerability of MRT-2359 administered orally over a 28-day cycle by the nature, incidence, and severity of all TEAEs, including treatment-related TEAEs and SAEs according to the NCI CTCAE, version 5.0

Analysis Window: 24 months

Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as DoR (in patients with the best overall response of CR or PR)

Analysis Window: 24 months

Phase 2 Dose Expansion further characterizes the PK profile of MRT-2359 by evaluating MRT-2359 plasma concentration to establish PK parameters including, but not limited to, Cmax, tmax, AUC0-t, AUC0inf, mean residence time, accumulation ratio, etc.

Analysis Window: 28 days

Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as DCR

Analysis Window: 24 months

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

Phase 1 Dose Escalation

EXPERIMENTAL

Patients with NSCLC, SCLC, high-grade neuroendocrine cancer of any primary site, any solid tumors with L-MYC or N-MYC amplification, or DLBCL

Phase 2 Expansion - NSCLC

EXPERIMENTAL

Patients with NSCLC with high or low L-MYC or N-MYC expression

Phase 2 Expansion - SCLC

EXPERIMENTAL

Patients with SCLC

Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors

EXPERIMENTAL

Patients with L-MYC or N-MYC amplified solid tumors

Phase 2 Expansion - HR-positive, HER2-negative breast cancer

EXPERIMENTAL

Patients with HR-positive, HER2-negative breast cancer in combination with fulvestrant

Phase 2 Expansion - Prostate Cancer

EXPERIMENTAL

Patients with prostate cancer in combination with enzalutamide

[DOSING_&_INTERVENTION_SPECIFICITIES]

Oral MRT-2359DRUG

Orally administered tablets of MRT-2359.

Oral MRT-2359DRUG

Orally administered tablets of MRT-2359.

Oral MRT-2359DRUG

Orally administered tablets of MRT-2359.

Oral MRT-2359DRUG

Orally administered tablets of MRT-2359.

Oral MRT-2359DRUG

Orally administered tablets of MRT-2359 in conjunction with intramuscular administration of fulvestrant.

Oral MRT-2359DRUG

Orally administered tablets of MRT-2359 in conjunction with orally administered enzalutamide.

[BIOCHEMICAL_STRUCTURE_REGISTRY]

MOLECULAR FORMULAC22H17F4N3O6

MOLECULAR WEIGHT495.4 g/mol

PARTITION (XLogP)2.5

H-BOND DONORS2

H-BOND ACCEPTORS10

COMPLEXITY SCORE856

SMILES (CANONICAL / ISOMERIC)

C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=C(C=C3)COC(=O)NC4=C(C=CC(=C4)OC(F)(F)F)F

INCHI KEYHNTGMIGBGVFOBT-UHFFFAOYSA-N

3D_CONFORMER_VIEWPORT

View Registry Record in PubChem [CID: 164584214] →