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Study of Oral MRT-2359 in Selected Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05546268
Recruitment Status : Recruiting
First Posted : September 19, 2022
Last Update Posted : May 8, 2024
Sponsor:
Information provided by (Responsible Party):
Monte Rosa Therapeutics, Inc

Brief 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.

Condition or disease Intervention/treatment Phase
NSCLC SCLC High Grade Neuroendocrine Cancer DLBCL L-MYC and N-MYC Amplified Solid Tumors NSCLC With High or Low L-MYC or N-MYC Expression HR-positive, HER2-negative Breast Cancer Prostate Cancer Drug: Oral MRT-2359 Phase 1 Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Single Group
Masking: None (Open Label)
Masking Description: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 12, 2022
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : November 2027


Arm Intervention/treatment
Experimental: Phase 1 Dose Escalation
Patients with NSCLC, SCLC, high-grade neuroendocrine cancer of any primary site, any solid tumors with L-MYC or N-MYC amplification, or DLBCL
Drug: Oral MRT-2359
Orally administered tablets of MRT-2359.

Experimental: Phase 2 Expansion - NSCLC
Patients with NSCLC with high or low L-MYC or N-MYC expression
Drug: Oral MRT-2359
Orally administered tablets of MRT-2359.

Experimental: Phase 2 Expansion - SCLC
Patients with SCLC
Drug: Oral MRT-2359
Orally administered tablets of MRT-2359.

Experimental: Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors
Patients with L-MYC or N-MYC amplified solid tumors
Drug: Oral MRT-2359
Orally administered tablets of MRT-2359.

Experimental: Phase 2 Expansion - HR-positive, HER2-negative breast cancer
Patients with HR-positive, HER2-negative breast cancer in combination with fulvestrant
Drug: Oral MRT-2359
Orally administered tablets of MRT-2359 in conjunction with intramuscular administration of fulvestrant.

Experimental: Phase 2 Expansion - Prostate Cancer
Patients with prostate cancer in combination with enzalutamide
Drug: Oral MRT-2359
Orally administered tablets of MRT-2359 in conjunction with orally administered enzalutamide.




Primary Outcome Measures :
  1. 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 [ Time Frame: 28 days ]
  2. Phase 2 Evaluates preliminary anti-tumor activity of MRT-2359 by overall response rate (ORR) as determined by RECIST 1.1 [ Time Frame: 56 days (up to approximately 24 months from screening to end of study participation ]

Secondary Outcome Measures :
  1. 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) [ Time Frame: 18 months ]
  2. 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 [ Time Frame: 18 months ]
  3. 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 [ Time Frame: 28 days ]
  4. 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 [ Time Frame: 7 days ]
  5. 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 [ Time Frame: 24 months ]
  6. 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) [ Time Frame: 24 months ]
  7. 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. [ Time Frame: 28 days ]
  8. Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as DCR [ Time Frame: 24 months ]
  9. Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as PFS [ Time Frame: 24 months ]
  10. Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as OS [ Time Frame: 24 months ]
  11. Phase 2 Dose Expansion evaluates additional measures of the preliminary anti-tumor activity of MRT-2359 such as PSA response [ Time Frame: 24 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05546268


Contacts
Layout table for location contacts
Contact: Monte Rosa Therapeutics 617-865-4792 Clinicaltrials@monterosatx.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Monte Rosa Therapeutics, Inc
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Responsible Party: Monte Rosa Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT05546268    
Other Study ID Numbers: MRT-2359-001
First Posted: September 19, 2022    Key Record Dates
Last Update Posted: May 8, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Monte Rosa Therapeutics, Inc:
High-grade neuroendocrine
Small Cell Lung Cancer
Non-Small Cell Lung Cancer
L-MYC Amplification
N-MYC Amplification
L-MYC expression
N-MYC expression
Diffuse Large B-Cell Lymphoma
Molecular glue degrader
Anti-tumor
GSPT1
HR-positive
HER2-negative
Breast Cancer
Prostate Cancer
Additional relevant MeSH terms:
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Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Prostatic Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue