Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05546268
Other study ID # MRT-2359-001
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date October 12, 2022
Est. completion date November 2027

Study information

Verified date April 2024
Source Monte Rosa Therapeutics, Inc
Contact Monte Rosa Therapeutics
Phone 617-865-4792
Email Clinicaltrials@monterosatx.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This Phase 1/2, open-label, multicenter study is conducted in patients with previously treated selected solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), high-grade neuroendocrine cancer of any primary site, diffuse large B-cell lymphoma (DLBCL), and tumors with L-MYC or N-MYC amplification. Patients receive escalating doses of a GSPT1 molecular glue degrader MRT-2359 to determine safety, tolerability, maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of MRT-2359. Once the MTD and/or RP2D is identified, additional patients enroll to Phase 2 study, which includes molecular biomarkers stratification or selection, namely expression or amplification of L-MYC and N-MYC genes, hormone receptor positive (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer and prostate cancer.


Description:

This Phase 1/2, open-label, multicenter, dose escalation and expansion study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary clinical activity of MRT-2359 in patients with previously treated selected solid tumors, including lung cancer (NSCLC and SCLC), high-grade neuroendocrine cancer of any primary site, and DLBCL. - The primary aim of Phase 1 part is safety, tolerability, MTD and/or RP2D of MRT-2359. - The primary aim of Phase 2 part is assessment of preliminary anti-tumor activity of MRT-2359.


Recruitment information / eligibility

Status Recruiting
Enrollment 174
Est. completion date November 2027
Est. primary completion date May 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Phase 1 enrollment population: - NSCLC - SCLC - High-grade neuroendocrine cancer of any primary site - Any solid tumors with L-MYC or N-MYC amplification - DLBCL Phase 2 enrollment population: - Any solid tumors with L-MYC or N-MYC amplification - NSCLC with high or low L-MYC or N-MYC expression status (testing will be provided) or SCLC - HR-positive, HER2-negative breast cancer - MRT-2359 in combination with fulvestrant - Non-neuroendocrine prostate cancer - MRT-2359 in combination with enzalutamide Phase 1 and Phase 2 Inclusion Criteria: - Have a selected advanced solid tumor or DLBCL (listed above) for which there are no further standard therapeutic options available - Be age = 18 years and willing to voluntarily complete the informed consent process - A predicted life expectancy of = 3 months and an ECOG performance status = 2 - Have measurable disease by RECIST 1.1 (Eisenhauer et al., 2009) in case of solid tumors or Revised Response Criteria for Malignant Lymphoma (Phase 1 only) (Cheson et al., 2014) in case of DLBCL - Have adequate organ function defined by the selected laboratory parameters - If female of childbearing potential, avoid becoming pregnant and agree to use acceptable methods of contraception after informed consent, throughout the study, and for 90 days after the last dose of MRT-2359 - Male of reproductive potential must use an approved methods of contraception from informed consent until 90 days after study discharge Exclusion Criteria: - Have received prior chemotherapy, definitive radiation, biological cancer therapy or any investigational agent within 21 days before the first dose of study treatment, or have any AEs that have failed to recover to baseline. In patients with prostate cancer, continuance of systemic therapies to maintain castration levels of testosterone is allowed. Pre-menopausal patients with hormone-dependent breast cancer can continue on therapies used for suppression of ovarian function. - Have received bisphosphonates or denosumab within 14 days before the first administration of the study drug unless they were given for acute hypercalcemia - Inability to swallow oral medication - Have received prior therapy with a GSPT1 degrader that was discontinued due to an AE - Have received prior auto-HCT and not fully recovered from effects of the last transplant - Have received prior allogeneic hematopoietic stem cell transplantation within past 6 months and/or have symptoms of graft-versus-host disease. Patients requiring minimal intervention such as topical steroids are eligible - Have received a live vaccine within 90 days before the first dose of study treatment - COVID-19 immunization within 14 days of receiving the first dose of MRT-2359 - Current use of chronic systemic steroid therapy in excess of replacement doses (prednisone = 10 mg/day is acceptable) - Have clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug - Have a history of a second malignancy, unless controlled not requiring therapy - Have clinically active central nervous system involvement and/or carcinomatous meningitis. Patients with treated and stable brain metastases (not progressing for at least 4 weeks prior to enrollment) not requiring steroids are eligible - Have a confirmed history of (non-infectious) pneumonitis that required steroids - Have known human immunodeficiency virus (HIV) unless the patient is on antiviral therapy with undetectable HIV RNA levels - Have known hepatitis B or C infection(s) unless treated with undetectable hepatitis B DNA or hepatitis C RNA levels - Clinically significant cardiac disease - Be pregnant or breastfeeding

Study Design


Intervention

Drug:
Oral MRT-2359
Orally administered tablets of MRT-2359.
Oral MRT-2359
Orally administered tablets of MRT-2359.
Oral MRT-2359
Orally administered tablets of MRT-2359.
Oral MRT-2359
Orally administered tablets of MRT-2359.
Oral MRT-2359
Orally administered tablets of MRT-2359 in conjunction with intramuscular administration of fulvestrant.
Oral MRT-2359
Orally administered tablets of MRT-2359 in conjunction with orally administered enzalutamide.

Locations

Country Name City State
Canada Cross Cancer Institute Edmonton Alberta
Canada Princess Margaret Hospital Toronto Ontario
United States Indiana University Bloomington Indiana
United States Dana Farber Cancer Institute Boston Massachusetts
United States Mary Crowley Cancer Research Dallas Texas
United States Henry Ford Cancer Institute Detroit Michigan
United States Virginia Cancer Specialists Research Institute Fairfax Virginia
United States MD Anderson Cancer Center Houston Texas
United States Sarah Cannon Research Institute Lake Mary Florida
United States University of Kansas Cancer Center Lawrence Kansas
United States Sarah Cannon Research Institute Nashville Tennessee
United States Yale University New Haven Connecticut
United States Columbia University Irving Medical Centre New York New York
United States Memorial Sloan Kettering Cancer Center New York New York
United States Hoag Memorial Hospital Presbyterian Newport Beach California
United States Washington University Saint Louis Missouri
United States South Texas Accelerated Research Therapeutics (START) San Antonio Texas
United States University of California San Diego San Diego California
United States Honor Health Research Institute Scottsdale Arizona
United States Fred Hutchinson Cancer Center Seattle Washington
United States Moffitt Cancer Center Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Monte Rosa Therapeutics, Inc

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 28 days
Primary Phase 2 Evaluates preliminary anti-tumor activity of MRT-2359 by overall response rate (ORR) as determined by RECIST 1.1 56 days (up to approximately 24 months from screening to end of study participation
Secondary 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) 18 months
Secondary 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 18 months
Secondary 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 28 days
Secondary 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 7 days
Secondary 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 24 months
Secondary 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) 24 months
Secondary 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. 28 days
Secondary Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as DCR 24 months
Secondary Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as PFS 24 months
Secondary Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as OS 24 months
Secondary Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as PSA response 24 months
See also
  Status Clinical Trial Phase
Recruiting NCT05540392 - An Acupuncture Study for Prostate Cancer Survivors With Urinary Issues Phase 1/Phase 2
Recruiting NCT05613023 - A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT Phase 3
Recruiting NCT05156424 - A Comparison of Aerobic and Resistance Exercise to Counteract Treatment Side Effects in Men With Prostate Cancer Phase 1/Phase 2
Completed NCT03177759 - Living With Prostate Cancer (LPC)
Completed NCT01331083 - A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer Phase 2
Recruiting NCT05540782 - A Study of Cognitive Health in Survivors of Prostate Cancer
Active, not recruiting NCT04742361 - Efficacy of [18F]PSMA-1007 PET/CT in Patients With Biochemial Recurrent Prostate Cancer Phase 3
Completed NCT04400656 - PROState Pathway Embedded Comparative Trial
Completed NCT02282644 - Individual Phenotype Analysis in Patients With Castration-Resistant Prostate Cancer With CellSearch® and Flow Cytometry N/A
Recruiting NCT06305832 - Salvage Radiotherapy Combined With Androgen Deprivation Therapy (ADT) With or Without Rezvilutamide in the Treatment of Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer Phase 2
Recruiting NCT06037954 - A Study of Mental Health Care in People With Cancer N/A
Recruiting NCT05761093 - Patient and Physician Benefit/ Risk Preferences for Treatment of mPC in Hong Kong: a Discrete Choice Experiment
Completed NCT04838626 - Study of Diagnostic Performance of [18F]CTT1057 for PSMA-positive Tumors Detection Phase 2/Phase 3
Recruiting NCT03101176 - Multiparametric Ultrasound Imaging in Prostate Cancer N/A
Completed NCT03290417 - Correlative Analysis of the Genomics of Vitamin D and Omega-3 Fatty Acid Intake in Prostate Cancer N/A
Completed NCT00341939 - Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
Completed NCT01497925 - Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer Phase 1
Recruiting NCT03679819 - Single-center Trial for the Validation of High-resolution Transrectal Ultrasound (Exact Imaging Scanner ExactVu) for the Detection of Prostate Cancer
Completed NCT03554317 - COMbination of Bipolar Androgen Therapy and Nivolumab Phase 2
Completed NCT03271502 - Effect of Anesthesia on Optic Nerve Sheath Diameter in Patients Undergoing Robot-assisted Laparoscopic Prostatectomy N/A