Study of Oral MRT-2359 in Selected Cancer Patients

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