Trial Title:
Study of Oral MRT-2359 in Selected Cancer Patients
NCT ID:
NCT05546268
Condition:
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
Conditions: Official terms:
Prostatic Neoplasms
Carcinoma, Neuroendocrine
Conditions: Keywords:
Small Cell Lung Cancer
Non-Small Cell Lung Cancer
L-MYC Amplification
N-MYC Amplification
L-MYC expression
N-MYC expression
High-grade neuroendocrine
Diffuse Large B-Cell Lymphoma
Molecular glue degrader
Anti-tumor
GSPT1
HR-positive
HER2-negative
Breast Cancer
Prostate Cancer
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
Single Group
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Oral MRT-2359
Description:
Orally administered tablets of MRT-2359.
Arm group label:
Phase 1 Dose Escalation
Intervention type:
Drug
Intervention name:
Oral MRT-2359
Description:
Orally administered tablets of MRT-2359.
Arm group label:
Phase 2 Expansion - NSCLC
Intervention type:
Drug
Intervention name:
Oral MRT-2359
Description:
Orally administered tablets of MRT-2359.
Arm group label:
Phase 2 Expansion - SCLC
Intervention type:
Drug
Intervention name:
Oral MRT-2359
Description:
Orally administered tablets of MRT-2359.
Arm group label:
Phase 2 Expansion - L-MYC or N-MYC amplified solid tumors
Intervention type:
Drug
Intervention name:
Oral MRT-2359
Description:
Orally administered tablets of MRT-2359 in conjunction with intramuscular administration
of fulvestrant.
Arm group label:
Phase 2 Expansion - HR-positive, HER2-negative breast cancer
Intervention type:
Drug
Intervention name:
Oral MRT-2359
Description:
Orally administered tablets of MRT-2359 in conjunction with orally administered
enzalutamide.
Arm group label:
Phase 2 Expansion - Prostate Cancer
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.
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.
Criteria for eligibility:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Honor Health Research Institute
Address:
City:
Scottsdale
Zip:
85258
Country:
United States
Status:
Recruiting
Facility:
Name:
Hoag Memorial Hospital Presbyterian
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Status:
Recruiting
Facility:
Name:
University of California San Diego
Address:
City:
San Diego
Zip:
92037
Country:
United States
Status:
Recruiting
Facility:
Name:
Yale University
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
Lake Mary
Zip:
32746
Country:
United States
Status:
Recruiting
Facility:
Name:
Indiana University
Address:
City:
Bloomington
Zip:
46202
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Kansas Cancer Center
Address:
City:
Lawrence
Zip:
66044
Country:
United States
Status:
Recruiting
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Facility:
Name:
Henry Ford Cancer Institute
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Recruiting
Facility:
Name:
Columbia University Irving Medical Centre
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
Mary Crowley Cancer Research
Address:
City:
Dallas
Zip:
75251
Country:
United States
Status:
Recruiting
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030-4009
Country:
United States
Status:
Recruiting
Facility:
Name:
South Texas Accelerated Research Therapeutics (START)
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Facility:
Name:
Virginia Cancer Specialists Research Institute
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Facility:
Name:
Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Facility:
Name:
Cross Cancer Institute
Address:
City:
Edmonton
Zip:
T6G 1Z2
Country:
Canada
Status:
Recruiting
Facility:
Name:
Princess Margaret Hospital
Address:
City:
Toronto
Zip:
M5G 2C4
Country:
Canada
Status:
Recruiting
Start date:
October 12, 2022
Completion date:
November 2027
Lead sponsor:
Agency:
Monte Rosa Therapeutics, Inc
Agency class:
Industry
Source:
Monte Rosa Therapeutics, Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05546268
