Study of PCLX-001 in R/R Advanced Solid Malignancies and B-cell Lymphoma

Inclusion Criteria

• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained before any study-specific procedures are performed.
• Male or female patients aged ≥ 18 years
• Dose Escalation
• Participants with histologically-confirmed advanced solid tumor who have failed at least one prior therapy and/or are not eligible for therapies expected to provide clinical benefit.
• Histologically-confirmed B-cell lymphomas that are expected to express CD20 including DLBCL, HGBL, FL (grades 1 to 3b), MCL, and Burkitt lymphoma who have failed at least two prior therapies and/or are not eligible for therapies expected to provide clinical benefit (including autologous stem cell transplantation). Transformed large B-cell lymphoma patients are eligible. FL patients should meet criteria for requiring treatment.

Dose Expansion Cohort A: Participants with histologically-confirmed advanced breast, NSCLC, SCLC, colorectal, and bladder cancers who have failed at least one prior therapy and/or are not eligible for therapies expected to provide clinical benefit.

Cohort B: Participants with histologically-confirmed R/R B-cell lymphomas that are expected to express CD20 including DLBCL, HGBL, FL (grades 1-3a), FL (grade 3b), MCL, and Burkitt lymphoma who have failed at least two prior therapies and/or are not eligible for therapies expected to provide clinical benefit. Transformed large B-cell lymphoma patients are eligible. FL patients should meet criteria for requiring treatment.

• Patients must have evaluable or measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Life expectancy of at least 12 weeks
• Patients must have adequate bone marrow, liver, kidney and cardiac function.
• Patients must have adequate coagulation.
• Women of childbearing potential must have a negative pregnancy test.
• Women of childbearing potential and fertile men must agree to use adequate contraception when sexually active from signing of the informed consent form for the full study until at least 6 months after the last study drug administration.

Exclusion Criteria

• Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study.
• History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class > II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry, or uncontrolled cardiac arrhythmias.
• Uncontrolled arterial hypertension despite optimal medical management.
• Moderate or severe hepatic impairment.
• Patients with known human immunodeficiency virus (HIV) infection.
• Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
• Infections not responding to therapy or active clinically serious infections.
• Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months from definitive therapy, has a stable imaging study and is clinically stable. Patients with asymptomatic brain metastases must not be on steroid therapy.
• Current or past history of central nervous system (CNS) lymphoma.
• Uncontrolled seizure disorder requiring therapy.
• History of organ allograft transplantation or autologous stem cell transplantation ≤ 3 months prior to the first dose of study drug. Patients who received prior CAR-T or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to study drug administration.
• Evidence or history of bleeding disorder within 4 weeks before the first dose of study drug.
• Serious, non-healing wound, ulcer, or bone fracture.
• Any malabsorption condition.
• Breastfeeding. Female patients must not breastfeed during treatment and until 4 months after last study drug administration.
• Treatment with systemic ster