Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Conditions
Keywords
Phase 1, Safety, Apilimod dimesylate, Pharmacokinetics, Non-Hodgkin Lymphoma, Chronic lymphocytic leukemia
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.
Interventions
DRUGLAM-002A
25 mg capsules or 50 mg capsules
DRUGRituximab
375 mg/m2 by vein
DRUGAtezolizumab
1200 mg by vein
Sponsors
OrphAI Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to understand and comply with the protocol requirements and has signed the informed consent document. 2. 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. 3. 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 4. 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) 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less. 6. Adequate organ and marrow function. 7. Able to swallow oral capsules without difficulty. 8. Acceptable birth control. 9. Women of childbearing potential : negative pregnancy test 10. Adequate archival or fresh tumor tissue (from biopsy, bone marrow, or peripheral blood) for analysis of potential predictive biomarkers.
Exclusion criteria
1. 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. 2. Not recovered from toxicity due to all prior therapies. 3. Other uncontrolled significant illness. 4. History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of LAM-002A 5. Major surgery within 28 days prior to first dose of study drug. 6. Past history of tuberculosis (TB) or active infection with TB, human immunodeficiency virus (HIV), hepatitis B or hepatitis C. 7. Lactation or breast feeding. 8. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 12 study centers in the United States, 11 of which enrolled subjects to the trial.
Participants by arm
| Arm | Count |
|---|---|
| LAM-002A Continuous Monotherapy - 50 mg BID All participants took 50 mg LAM-002A two times daily by mouth every day until cancer progression or intolerability.
LAM-002A: 25 mg capsules or 50 mg capsules | 3 |
| LAM-002A Continuous Monotherapy - 100 mg BID All participants took 100 mg LAM-002A two times daily by mouth every day until cancer progression or intolerability.
LAM-002A: 25 mg capsules or 50 mg capsules | 8 |
| LAM-002A Continuous Monotherapy - 150 mg BID All participants took 150 mg LAM-002A two times daily by mouth every day until cancer progression or intolerability.
LAM-002A: 25 mg capsules or 50 mg capsules | 5 |
| LAM-002A Continuous Monotherapy - 75 mg TID All participants took 75 mg LAM-002A three times daily by mouth every day until cancer progression or intolerability.
LAM-002A: 25 mg capsules or 50 mg capsules | 4 |
| LAM-002A Intermittent Monotherapy - 150 mg BID All participants received LAM-002A at 150 mg two times daily by mouth for 3 days on therapy followed by 4 days off therapy every week until cancer progression or intolerability.
LAM-002A: 25 mg capsules or 50 mg capsules | 3 |
| LAM-002A Continuous Monotherapy - 125 mg All participants took 125 mg LAM-002A two times daily by mouth every day until cancer progression or intolerability.
LAM-002A: 25 mg capsules or 50 mg capsules | 20 |
| LAM-002A + Rituximab All participants received LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and rituximab by vein (IV) every week for 4 weeks and then every 8 weeks for 4 times (total of 8 infusions) or one dose of rituximab IV followed by rituximab subcutaneous (SC) for 3 weeks and then SC every 8 weeks for 4 times (total of 8 doses).
Rituximab: 375 mg/m\^2 IV or rituximab (hyaluronidase) (1,400 mg rituximab and 23,400 Units hyaluronidase human) SC | 12 |
| LAM-002A + Atezolizumab All participants received 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
Atezolizumab: 1200 mg by vein | 7 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 4 | 1 | 0 | 6 | 1 | 1 |
| Overall Study | Disease Progression | 3 | 7 | 0 | 2 | 2 | 12 | 5 | 5 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 |
| Overall Study | Progressive Leukocytosis | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Substantial noncompliance | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | LAM-002A Continuous Monotherapy - 50 mg BID | LAM-002A Continuous Monotherapy - 100 mg BID | LAM-002A Continuous Monotherapy - 150 mg BID | LAM-002A Continuous Monotherapy - 75 mg TID | LAM-002A Intermittent Monotherapy - 150 mg BID | LAM-002A Continuous Monotherapy - 125 mg | LAM-002A + Rituximab | LAM-002A + Atezolizumab | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized Age Category <65 years | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 9 Participants | 7 Participants | 2 Participants | 24 Participants |
| Age, Customized Age Category ≥65 years | 1 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 11 Participants | 5 Participants | 5 Participants | 38 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0, fully active, able to carry on all predisease performance without restrictions | 0 Participants | 5 Participants | 1 Participants | 1 Participants | 1 Participants | 7 Participants | 3 Participants | 0 Participants | 18 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1, restricted in physically strenuous activity but ambulatory and able to do light or sedentary work | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 11 Participants | 9 Participants | 6 Participants | 39 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2, ambulatory and capable of all self-care but unable to work. Up more than 50% of waking hours | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3, capable of only limited self-care, confined to bed or chair more than 50% of waking hours | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic/Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic/Latino | 3 Participants | 8 Participants | 5 Participants | 3 Participants | 3 Participants | 16 Participants | 12 Participants | 7 Participants | 57 Participants |
| Race/Ethnicity, Customized Race Black/African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Race White | 3 Participants | 6 Participants | 4 Participants | 3 Participants | 3 Participants | 16 Participants | 11 Participants | 7 Participants | 53 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 4 Participants | 2 Participants | 2 Participants | 9 Participants | 4 Participants | 3 Participants | 30 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 11 Participants | 8 Participants | 4 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 8 | 1 / 5 | 0 / 4 | 0 / 3 | 3 / 20 | 0 / 12 | 3 / 7 |
| other Total, other adverse events | 3 / 3 | 8 / 8 | 5 / 5 | 4 / 4 | 3 / 3 | 20 / 20 | 12 / 12 | 7 / 7 |
| serious Total, serious adverse events | 0 / 3 | 3 / 8 | 1 / 5 | 2 / 4 | 0 / 3 | 9 / 20 | 5 / 12 | 6 / 7 |
Outcome results
Primary
Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A
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).
Time frame: 28 days
Population: Full analysis set=All subjects who receive ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Determination of the Maximum Tolerated Dose (MTD) of Continuous Oral LAM-002A | 125 mg BID |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A
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.
Time frame: 8 days
Population: The PK population included all evaluable subjects who were dosed and had sufficient concentration-time data to estimate ≥1 of the planned PK parameters, as determined by the study pharmacokineticist.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 1 | 542 h*ng/mL | Standard Deviation 214 |
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 8 | 374 h*ng/mL | Standard Deviation 119 |
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 1 | 238 h*ng/mL | Standard Deviation 88.1 |
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 8 | 653 h*ng/mL | Standard Deviation 365 |
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 1 | 312 h*ng/mL | Standard Deviation 156 |
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 8 | 433 h*ng/mL | Standard Deviation 195 |
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 1 | 238 h*ng/mL | Standard Deviation 91.2 |
| All Participants | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 8 | 308 h*ng/mL | Standard Deviation 164 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 8 | 2070 h*ng/mL | Standard Deviation 1430 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 8 | 1040 h*ng/mL | Standard Deviation 780 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 1 | 583 h*ng/mL | Standard Deviation 290 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 1 | 280 h*ng/mL | Standard Deviation 216 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 8 | 1140 h*ng/mL | Standard Deviation 818 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 1 | 1020 h*ng/mL | Standard Deviation 659 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 8 | 1040 h*ng/mL | Standard Deviation 483 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 1 | 526 h*ng/mL | Standard Deviation 291 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 8 | 1130 h*ng/mL | Standard Deviation 930 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 1 | 1120 h*ng/mL | Standard Deviation 550 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 8 | 1810 h*ng/mL | Standard Deviation 1240 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 8 | 959 h*ng/mL | Standard Deviation 343 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 1 | 762 h*ng/mL | Standard Deviation 371 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 8 | 1360 h*ng/mL | Standard Deviation 796 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 1 | 622 h*ng/mL | Standard Deviation 372 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 1 | 515 h*ng/mL | Standard Deviation 221 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 1 | 443 h*ng/mL | Standard Deviation 325 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 8 | 1270 h*ng/mL | Standard Deviation 875 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 1 | 625 h*ng/mL | Standard Deviation 419 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 1 | 562 h*ng/mL | Standard Deviation 234 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 1 | 1180 h*ng/mL | Standard Deviation 587 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 8 | 1860 h*ng/mL | Standard Deviation 1160 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 8 | 746 h*ng/mL | Standard Deviation 509 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 8 | 1290 h*ng/mL | Standard Deviation 1040 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 8 | 556 h*ng/mL | Standard Deviation 397 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 1 | 700 h*ng/mL | Standard Deviation 290 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 1 | 936 h*ng/mL | Standard Deviation 734 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 8 | 1040 h*ng/mL | Standard Deviation 572 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 1 | 785 h*ng/mL | Standard Deviation 923 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 8 | 1060 h*ng/mL | Standard Deviation 85.7 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 1 | 1590 h*ng/mL | Standard Deviation 1420 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 8 | 1320 h*ng/mL | Standard Deviation 211 |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 8 | 760 h*ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 1 | 968 h*ng/mL | Standard Deviation 547 |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 1 | 1700 h*ng/mL | Standard Deviation 843 |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5944 - Day 8 | 1350 h*ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-5908 - Day 8 | 690 h*ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 8 | 563 h*ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | STA-6048 - Day 1 | 869 h*ng/mL | Standard Deviation 415 |
| LAM-002A Intermittent Monotherapy - 150 mg | Area Under the Plasma Concentration Versus Time Curve (AUC) of LAM-002A | Apilimod - Day 1 | 777 h*ng/mL | Standard Deviation 437 |
Secondary
Objective Response Rate
Anti-tumor response as assessed by investigator according to modified Hallek or Lugano Response Criteria by Disease Type and Cohort
Time frame: 1 cycle (28 days) up to a maximum of 24 cycles
Population: Full Analysis Set: All participants who received ≥1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| All Participants | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| All Participants | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| All Participants | Objective Response Rate | MZL (marginal zone lymphoma) | 0 Participants |
| All Participants | Objective Response Rate | FL (follicular lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 75 mg TID | Objective Response Rate | FL (follicular lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 75 mg TID | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 75 mg TID | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 75 mg TID | Objective Response Rate | MZL (marginal zone lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 75 mg TID | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 100 mg BID | Objective Response Rate | FL (follicular lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 100 mg BID | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 100 mg BID | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 100 mg BID | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 100 mg BID | Objective Response Rate | MZL (marginal zone lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 125 mg BID | Objective Response Rate | MZL (marginal zone lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 125 mg BID | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 125 mg BID | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 125 mg BID | Objective Response Rate | FL (follicular lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 125 mg BID | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 150 mg BID | Objective Response Rate | MZL (marginal zone lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 150 mg BID | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 150 mg BID | Objective Response Rate | FL (follicular lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 150 mg BID | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| LAM-002A Continuous Monotherapy - 150 mg BID | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| LAM-002A Intermittent Monotherapy - 150 mg | Objective Response Rate | MZL (marginal zone lymphoma) | 0 Participants |
| LAM-002A Intermittent Monotherapy - 150 mg | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| LAM-002A Intermittent Monotherapy - 150 mg | Objective Response Rate | FL (follicular lymphoma) | 2 Participants |
| LAM-002A Intermittent Monotherapy - 150 mg | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| LAM-002A Intermittent Monotherapy - 150 mg | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| LAM-002A + Rituximab | Objective Response Rate | MZL (marginal zone lymphoma) | 1 Participants |
| LAM-002A + Rituximab | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| LAM-002A + Rituximab | Objective Response Rate | FL (follicular lymphoma) | 5 Participants |
| LAM-002A + Rituximab | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| LAM-002A + Rituximab | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| LAM-002A + Atezolizumab | Objective Response Rate | CLL/SLL (chronic lymphocytic leukemia/ small lymphocytic lymphoma) | 0 Participants |
| LAM-002A + Atezolizumab | Objective Response Rate | MCL (mantle cell lymphoma) | 0 Participants |
| LAM-002A + Atezolizumab | Objective Response Rate | DLBCL (diffuse large B-cell lymphoma) | 0 Participants |
| LAM-002A + Atezolizumab | Objective Response Rate | MZL (marginal zone lymphoma) | 0 Participants |
| LAM-002A + Atezolizumab | Objective Response Rate | FL (follicular lymphoma) | 2 Participants |
Secondary
Peak Plasma Concentration (Cmax) of LAM-002A
Evaluation of the peak plasma concentration (Cmax) of LAM-002A and its metabolites in plasma on Day 1 and Day 8.
Time frame: 8 days
Population: The PK population included all evaluable subjects who were dosed and had sufficient concentration-time data to estimate ≥1 of the planned PK parameters, as determined by the study pharmacokineticist.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 1 | 112 ng/mL | Standard Deviation 85 |
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 8 | 140 ng/mL | Standard Deviation 95.1 |
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 1 | 117 ng/mL | Standard Deviation 69.6 |
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 8 | 103 ng/mL | Standard Deviation 43.7 |
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 1 | 209 ng/mL | Standard Deviation 145 |
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 8 | 188 ng/mL | Standard Deviation 101 |
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 1 | 63.2 ng/mL | Standard Deviation 40.2 |
| All Participants | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 8 | 60.6 ng/mL | Standard Deviation 32 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 8 | 239 ng/mL | Standard Deviation 195 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 8 | 154 ng/mL | Standard Deviation 113 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 1 | 158 ng/mL | Standard Deviation 61.6 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 1 | 59.9 ng/mL | Standard Deviation 54 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 8 | 436 ng/mL | Standard Deviation 334 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 1 | 114 ng/mL | Standard Deviation 71.6 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 8 | 339 ng/mL | Standard Deviation 215 |
| LAM-002A Continuous Monotherapy - 75 mg TID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 1 | 243 ng/mL | Standard Deviation 124 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 8 | 331 ng/mL | Standard Deviation 273 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 1 | 215 ng/mL | Standard Deviation 88.6 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 8 | 278 ng/mL | Standard Deviation 137 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 8 | 161 ng/mL | Standard Deviation 43 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 1 | 346 ng/mL | Standard Deviation 131 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 8 | 439 ng/mL | Standard Deviation 215 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 1 | 136 ng/mL | Standard Deviation 64.2 |
| LAM-002A Continuous Monotherapy - 100 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 1 | 263 ng/mL | Standard Deviation 168 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 1 | 90.0 ng/mL | Standard Deviation 58.6 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 8 | 383 ng/mL | Standard Deviation 225 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 1 | 281 ng/mL | Standard Deviation 125 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 1 | 207 ng/mL | Standard Deviation 82.4 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 1 | 144 ng/mL | Standard Deviation 92.5 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 8 | 234 ng/mL | Standard Deviation 173 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 8 | 122 ng/mL | Standard Deviation 81.7 |
| LAM-002A Continuous Monotherapy - 125 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 8 | 331 ng/mL | Standard Deviation 287 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 8 | 116 ng/mL | Standard Deviation 87.4 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 1 | 243 ng/mL | Standard Deviation 76.1 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 1 | 369 ng/mL | Standard Deviation 306 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 8 | 391 ng/mL | Standard Deviation 9.9 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 1 | 131 ng/mL | Standard Deviation 134 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 8 | 369 ng/mL | Standard Deviation 90.5 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 1 | 196 ng/mL | Standard Deviation 142 |
| LAM-002A Continuous Monotherapy - 150 mg BID | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 8 | 240 ng/mL | Standard Deviation 99.7 |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 8 | 140 ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 1 | 466 ng/mL | Standard Deviation 247 |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 1 | 207 ng/mL | Standard Deviation 135 |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5908 - Day 8 | 113 ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | STA-5944 - Day 8 | 260 ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 8 | 108 ng/mL | — |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | STA-6048 - Day 1 | 145 ng/mL | Standard Deviation 66 |
| LAM-002A Intermittent Monotherapy - 150 mg | Peak Plasma Concentration (Cmax) of LAM-002A | Apilimod - Day 1 | 280 ng/mL | Standard Deviation 135 |