A Phase 1/2 Study of Oral MRT-2359 in Selected Cancer Patients

Sponsor
Monte Rosa Therapeutics, Inc (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05546268
Collaborator
(none)
133
8
4
61
16.6
0.3

Study Details

Study Description

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 mRNA expression or amplification of L-MYC and N-MYC genes.

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
133 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
Single GroupSingle 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
Anticipated Study Start Date :
Oct 1, 2022
Anticipated Primary Completion Date :
May 1, 2026
Anticipated Study Completion Date :
Nov 1, 2027

Arms and Interventions

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 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)

Experimental: Phase 2 Expansion - NSCLC

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

Drug: Oral MRT-2359
Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)

Experimental: Phase 2 Expansion - SCLC

Patients with SCLC with high or low L-MYC or N-MYC mRNA expression

Drug: Oral MRT-2359
Orally administered tablets of MRT-2359 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)

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 taken once a day on Days 1 through 5 and Days 15 through 19 of a 28-day cycle (5 days of dosing followed by 9 days of no dose)

Outcome Measures

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 [28 days]

  2. 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 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 SAEs [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 [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 [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 [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 [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), DCR, PFS, and OS [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, AUC0-inf, mean residence time, accumulation ratio, etc. [28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 known amplification

  • NSCLC or SCLC with known L-MYC or N-MYC mRNA expression status (testing will be provided)

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

  • 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Honor Health Research Institute Scottsdale Arizona United States 85258
2 Indiana University Bloomington Indiana United States 46202
3 Dana Farber Cancer Institute Boston Massachusetts United States 02215
4 Memorial Sloan Kettering Cancer Center New York New York United States 10021
5 Sarah Cannon Research Institute Nashville Tennessee United States 37203
6 Mary Crowley Cancer Research Dallas Texas United States 75251
7 MD Anderson Cancer Center Houston Texas United States 77030-4009
8 South Texas Accelerated Research Therapeutics (START) San Antonio Texas United States 78229

Sponsors and Collaborators

  • Monte Rosa Therapeutics, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Monte Rosa Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT05546268
Other Study ID Numbers:
  • MRT-2359-001
First Posted:
Sep 19, 2022
Last Update Posted:
Sep 19, 2022
Last Verified:
Sep 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 19, 2022