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

Phase 1

Completed

Brief Summary: This is a Phase 1 dose-exploration study of LAM-002A administered by mouth in patients with relapsed or refractory B-cell NHL. Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD),and preliminary anti-tumor activity will be evaluated.

Detailed Description: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Intermittent monotherapy	LAM-002A	All patients will receive LAM-002A at escalating dose levels two times daily by mouth for 3 days on therapy followed by 4 days off therapy every week until cancer progression or intolerability.
Continuous monotherapy	LAM-002A	All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability.
LAM-002A + rituximab	Rituximab	All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and rituximab 375 mg/m2 by vein every week for 4 weeks and then every 8 weeks for 4 times (total of 8 infusions)
LAM-002A + atezolizumab	Atezolizumab	All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and atezolizumab 1200 mg by vein every 3 weeks until cancer progression or intolerability

Primary Outcome Measures

Name	Time	Method
Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A	28 days	MTD was determined by testing increasing doses up to 125 mg twice a day or 75 mg three times a day orally on dose escalation cohorts with 3 to 6 participants each. In the dose escalation, the cohort sizes of 3 to 6 subjects allow evaluation of regimen safety using a standard definition of MTD (ie, the highest starting dose associated with DLT in \<33% of subjects during the first cycle of therapy) when administered continuously (daily administration) and then when administered intermittently (repeated courses of 3 days on and 4 days off).

Secondary Outcome Measures

Name	Time	Method
Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A	8 days	Evaluation of the Area under the concentration-time curve from time-zero to the time of the last quantifiable concentration (AUClast) of LAM-002ALAM-002A and its metabolites in plasma on Day 1 and Day 8.
Peak Plasma Concentration (Cmax) of LAM-002A	8 days	Evaluation of the peak plasma concentration (Cmax) of LAM-002A and its metabolites in plasma on Day 1 and Day 8.
Objective Response Rate	1 cycle (28 days) up to a maximum of 24 cycles	Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria by Disease Type and Cohort

Locations (10): Clearview Cancer Institute
🇺🇸
Huntsville, Alabama, United States
Winship Cancer Institute at Emory University
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Atlanta, Georgia, United States
Horizon Oncology Research, Inc.
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Lafayette, Indiana, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
New York University School of Medicine
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New York, New York, United States
Virginia Cancer Specialists
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Fairfax, Virginia, United States
Virginia Mason Medical Center
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Seattle, Washington, United States
University of Texas MD Anderson Cancer Center
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Houston, Texas, United States
Mayo Clinic
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Rochester, Minnesota, United States
Weill Cornell Medical College
🇺🇸
New York, New York, United States