A Phase I Dose Escalation Study of the Safety and Pharmacokinetics of LAM-002A In Patients With Non-Hodgkin's Lymphoma

LAM-002A is supplied as 25-mg or 50-mg capsules and will be administered two times daily or three times daily by mouth in repeated 28-day cycles. Patients will be advised to take the doses at the same time each day.

A 3 + 3 design will be utilized to define a maximum tolerated dose (MTD). The MTD is defined as the highest dose at which no more than 1 of 6 patients (i.e., < 33%) experiences a dose-limiting toxicity (DLT) in the dose cohort.

Once the dose and schedule are established, additional patients will be treated to better characterize the safety, tolerability,PK, PD, and anti-tumor activity of LAM-002A when administered alone or in combination with rituximab or atezolizumab.

Inclusion criteria

• Able to understand and comply with the protocol requirements and has signed the informed consent document.
• Confirmed diagnosis of B-cell Non-Hodgkin's lymphoma limited to follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), primary mediastinal B-cell lymphoma (PMBL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that has progressed and for which standard curative measures do not exist or are no longer effective. Prior therapy must have included a rituximab-based regimen.
• Patients with DLBCL: Cancer progression after transplant, or be unwilling, unable or not an appropriate candidate for an autologous stem cell or bone marrow transplant
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of 1 or more lesions that measure at least 2.0 cm in the longest dimension (as assessed radiographically)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less.
• Adequate organ and marrow function.
• Able to swallow oral capsules without difficulty.
• Acceptable birth control.
• Women of childbearing potential : negative pregnancy test
• Adequate archival or fresh tumor tissue (from biopsy, bone marrow, or peripheral blood) for analysis of potential predictive biomarkers.

Exclusion criteria

• Patients with central nervous system (CNS) lymphoma are not eligible for the trial unless the disease had been treated and the subject remains without symptoms with no active CNS lymphoma.
• Not recovered from toxicity due to all prior therapies.
• Other uncontrolled significant illness.
• History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of LAM-002A
• Major surgery within 28 days prior to first dose of study drug.
• Past history of tuberculosis (TB) or active infection with TB, human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
• Lactation or breast feeding.
• Unable or unwilling to abide by the study protocol or cooperate fully with the Investigator or designee.

This is a shortened list and additional criteria may apply.