Phase I/II, First in Human, Dose Escalation Trial of TL-895 Monotherapy in Subjects with Relapsed/Refractory B-Cell Malignancies and Expansion of TL-895 Monotherapy and Combination Therapy with Navtemadlin in Treatment-Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Subjects and Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Small Lymphocytic Lymphoma

Prior treatment

• Prior anticancer treatment with any BTK, MDM2 inhibitor or PI3K inhibitor
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
• Arms 1, 2, 5 and 7 - Prior therapy with: • Anticancer treatment with chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or with any other anticancer therapy within 28 days prior to first dose of study treatment. • Any investigational agent within 28 days prior to first dose of study treatment. Participation in observational study is permitted. • Allogeneic stem cell transplant or active graft versus host disease following allogeneic transplant within 6 months prior to first dose of study treatment. • Autologous stem cell transplant within the last 3 months prior to first dose of study treatment
• Arms 3, 4 and 6 – Any prior therapy used for treatment of CLL/SLL
• Received major surgical intervention within 28 days prior to first dose of study treatment, or history of major organ transplant.
• Subjects with active fever (temperature higher than 38.2°C [100.8°F]) within 14 days prior to the first dose of study treatment
  • For the full list of exclusion criteria please refer to the Protocol
• Subjects with indwelling surgical drains (e.g., peritoneal, CNS, or pleural)

Other illness

• Known history of central nervous system lymphoma or leukemia
• History of Richter’s transformation or prolymphocytic leukemia
• Having history of difficulty of swallowing, gastric or small bowel surgery with history of malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study treatment.
• Uncontrolled intercurrent illness including, but not limited to clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric illness/ social situations that would limit compliance with study requirements.
• Subjects with uncontrolled bacterial, fungal, parasitic, or viral infection. Subjects with acute bacterial infections requiring antibiotic use should not enroll until the infection is stable in the judgement of the treating physician; these subjects may be on antibiotics at time of screening
• Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Subjects with known history of human immunodeficiency virus (HIV)
• Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma.

Lab values

• Grade 2 or higher QTc prolongation (> 480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0]).

Other

• Women who are pregnant or breastfeeding.

• Adults ≥18 years of age
• Arms 1 and 2 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)
• Arms 3 and 4 - Subject population (treatment-naive CLL or treatment-naïve SLL)
• Arm 5 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)
• Arm 6 - Subject population (treatment-naive CLL or treatment-naïve SLL)
• Arm 7 - Subject population (relapsed/refractory CLL or relapsed/refractory SLL)
• For the full list of inclusion criteria please refer to the Protocol