Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin's Lymphomas

Inclusion Criteria:

• Patients must provide written informed consent.

• Patients with a diagnosis of R/R CLL or other B-cell neoplasms (i.e., ABC DLBCL, GCBDLBCL, Richter's transformation and tFL) who have no available approved therapies,or patients with a diagnosis of non-Hodgkin's lymphoma, which has relapsed and/or isrefractory to standard therapy. a. Patients with R/R CLL must have been exposed to Bruton's tyrosine kinase (BTK) orB-Cell CLL/Lymphoma 2 (BCL2) inhibitor-based therapy in prior lines of therapy butmust not have known Cys481 resistance mutation prior to study enrollment.

• Age ≥ 18 years.

• Life expectancy greater than 12 weeks.

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 0 or 1.

• Ability to swallow and retain capsules and/or tablets.

• Absence of uncontrolled intercurrent illnesses, including uncontrolled infections,cardiac conditions, or other organ dysfunctions.

• If the patient consents to an optional tumor biopsy, he/she must have a tumor thatcan be safely biopsied and undergo a baseline tumor biopsy procedure, or be willingto provide available archival tissue collected within 6 months of signing theInformed Consent Form (ICF), and one post-Cycle 1 treatment biopsy.

• Patients must have at least one target lesion according to Lugano Classification.Patients with R/R CLL are exempt from this requirement.

• Women of child-bearing potential must have a negative serum or urine pregnancy test.

• Women of child-bearing potential must agree to use 2 reliable methods ofcontraception beginning 4 weeks prior to the initiation of treatment, duringtherapy, and for at least 4 weeks after the last drug administration.

• Men must agree to use a latex or synthetic condom during sexual contact with apregnant female or a female of child-bearing potential, for the duration of thestudy and for at least 4 weeks after the last drug administration, even if they haveundergone a successful vasectomy.

Exclusion Criteria:

• Received prior systemic anticancer treatment within the following time frames:

1. Chemotherapy, immunotherapy, radiotherapy or any other investigational therapywithin 21 days prior to starting study treatment.

2. Targeted therapies within 5 biological half-lives prior to starting studytreatment.

• Patients with active infections requiring therapy are not eligible for entry intothe study until resolution of the infection; however, patients on prophylacticantibiotics, antifungals or antivirals are eligible for entry into the study.

• Pregnant or lactating individuals.

• Impaired hepatic or renal function as demonstrated by any of the followinglaboratory values:

1. Aspartate transaminase (AST) or alanine transaminase (ALT) > 2.5 x upper limitof normal (ULN); for patients with liver involvement, > 5 x ULN

2. Total bilirubin > 1.5 x ULN (Patients with a history of Gilbert's syndrome mayparticipate if total bilirubin is less than or equal to 3 x ULN and the AST/ALTand alkaline phosphatase meet the protocol-specified levels for eligibility)

3. Alkaline phosphatase > 2.5 x ULN

4. Glomerular filtration rate < 50 mL/min, as assessed using the standardmethodology at the investigating center (i.e., Cockcroft-Gault), or serumcreatinine > 1.5 x ULN

• International normalized ratio (INR) > 1.5 or other evidence of impaired hepaticsynthesis function.

• Absolute neutrophil count < 1.0 x 109/L or platelets < 100 x 109/L, unless due todisease-related bone marrow impairment as confirmed by bone marrow biopsy duringscreening or due to standard of care treatment within 2 months prior to signing ofinformed consent. Patients with bone marrow impairment will be excluded if theirabsolute neutrophil count (ANC) is < 0.5 x 109/L and platelets < 50 x 109/L.

• Previous allogeneic bone marrow transplant is restricted, unless transplant wasgreater than 3 months prior and there is no evidence of acute or chronic graftversus host disease.

• Central nervous system involvement with malignancy.

• Patients who have poorly controlled diabetes mellitus or whose glucose values cannotbe controlled with medical treatment.

• Current malignancies of another type, with the exception of adequately treated insitu cervical cancer and basal cell skin cancer, squamous cell carcinoma of the skinor other malignancies with no evidence of disease for 2 years or more.

• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B coreantibody, hepatitis B surface antigen, or hepatitis C antibody must have a negativepolymerase chain reaction (PCR) result before enrollment. Those who are PCR positivewill be excluded.

• Documented or known bleeding disorder.

• Requirement for anticoagulation treatment that increases INR or activated partialthromboplastin time above the normal range (low molecular weight heparin and heparinline flush allowed).

• Patients requiring the use of strong CYP3A4, CYP1A2, or P-gp inhibitors.

• Patients with a significant cardiovascular disease or condition, including:

1. myocardial infarction within 6 months of study entry,

2. New York Heart Association Class III or IV heart failure,

3. uncontrolled dysrhythmias or poorly controlled angina,

4. history of serious ventricular arrhythmia (ventricular fibrillation orventricular tachycardia, ≥ 3 beats in a row) and/or risk factors (e.g., heartfailure, hypokalemia, or family history of Long QT Syndrome),

5. baseline prolongation of QT/QTc interval (repeated demonstration of correctedQT interval (QTc) ≥ 450 msec for men and 470 msec for women), and

6. left ventricular ejection fraction (LVEF) < 45% by multiple gated acquisition (MUGA) and /or echocardiogram (ECHO).