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 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 nofurther 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 solidtumors or Revised Response Criteria for Malignant Lymphoma (Phase 1 only) (Cheson etal., 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 useacceptable 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 frominformed consent until 90 days after study discharge

Exclusion Criteria:

• Have received prior chemotherapy, definitive radiation, biological cancer therapy orany 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 prostatecancer, continuance of systemic therapies to maintain castration levels oftestosterone is allowed. Pre-menopausal patients with hormone-dependent breastcancer can continue on therapies used for suppression of ovarian function.

• Have received bisphosphonates or denosumab within 14 days before the firstadministration 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 lasttransplant

• Have received prior allogeneic hematopoietic stem cell transplantation within past 6months and/or have symptoms of graft-versus-host disease. Patients requiring minimalintervention 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 likelyto 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 carcinomatousmeningitis. Patients with treated and stable brain metastases (not progressing forat 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 antiviraltherapy with undetectable HIV RNA levels

• Have known hepatitis B or C infection(s) unless treated with undetectable hepatitisB DNA or hepatitis C RNA levels

• Clinically significant cardiac disease

• Be pregnant or breastfeeding