Brief Title
Study of Oral Administration of LP-168 in Patients With Relapsed or Refractory B-cell Malignancies.
Official Title
A Phase I, Multicenter, Open-Label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-168 in Subjects With Relapsed or Refractory B-cell Malignancies.
Brief Summary
This is a phase I, multi-center, open-label, dose-escalation study to evaluate the safety,
tolerability, pharmacokinetics and clinical activity of LP-168 in subjects with relapsed or
refractory B-cell malignancies. LP-168 is a small molecule inhibitor.
Detailed Description
The primary objectives for the study are to assess the safety and tolerability profile,
determine the maximum tolerated dose (MTD), and/or the recommended Phase 2 dose (RP2D) of
LP-168 administered once or twice daily as a single agent dosed orally in adult subjects with
relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL); and to
characterize the pharmacokinetics (PK) profile of LP-168 in adult subjects with
relapsed/refractory B-cell Malignancies (CLL/SLL, WM, FL, MCL, MZL, DLBCL, HCL).
Secondary objectives of the study are to evaluate preliminary efficacy regarding the effect
of LP-168 on progression-free survival (PFS), objective response rate (ORR), and duration of
response (DOR) in adult subjects with relapsed/refractory B-cell Malignancies (CLL/SLL, WM,
FL, MCL, MZL, DLBCL, HCL).
Once the MTD is declared and the RP2D is established, additional subjects will be enrolled in
a cohort expansion phase (Phase 1b).
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum Tolerated Dose (MTD)
Secondary Outcome
Progression-Free Survival (PFS)
Condition
CLL/SLL
Intervention
LP-168
Study Arms / Comparison Groups
Dose Escalation Phase
Description: Three to six subjects per treatment cohort will be assigned to receive sequentially higher oral doses of LP-168 on a once or twice daily schedule for 28 days, starting at a dose of 100 mg/day.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
July 19, 2021
Completion Date
July 2023
Primary Completion Date
July 2023
Eligibility Criteria
Inclusion Criteria:
A subject will be eligible for study participation if he/she meets the following criteria:
- Subjects are eligible with B-cell malignancies, WM, FL, MCL, MZL, DLBCL, HCL, CLL,
SLL, based upon 2016 updated WHO classification. Those subjects with WM, FL, MCL,
DLBCL, or HCL must have received at least 2 prior systemic therapies.
- Low-grade B-cell lymphomas as follicular Grade 1, 2, or 3A, marginal zone or small
lymphocytic lymphoma.
- Subject must have adequate coagulation, renal, and hepatic function, per local
laboratory reference ranges at Screening as follows:
- Activated partial thromboplastin time (APTT) and prothrombin time (PT) not to
exceed 1.5 × ULN
- Calculated creatinine clearance (CrCl) ≥ 60 mL/min using 24-hour CrCl OR
Cockcroft-Gault formula.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 ×ULN;
Bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome, who may have a
bilirubin > 1.5 × ULN, per discussion between the Investigator and the Medical
Monitor).
- Subjects must have adequate bone marrow independent of growth factor support per local
laboratory reference range at screening as follows:
- Absolute Neutrophil Count (ANC) ≥1000/uL;
- An exception is for subjects with an ANC<1000/uL and bone marrow heavily
infiltrated with underlying disease (approximately 60% or more) may use growth
factor to achieve the ANC eligibility criteria per discussion between the
Investigator and the Medical Monitor.
- Platelet count ≥ 50,000/µL - OR - Platelet count ≥ 20,000/ µL if thrombocytopenia
is clearly due to CLL disease under study (per Investigator discretion)
- Hemoglobin ≥8.0g/dL, and can be achieved by transfusion
Exclusion Criteria:
A subject will not be eligible for study participation if he/she meets any of the following
criteria.
- Subject has received any of the following therapies within 14 days or 5 half-lives
(whichever is shorter) prior to the first dose of study drug, or has not recovered to
≤ Grade 1 clinically significant adverse effect(s)/toxicity(s) of the previous therapy
(other than alopecia):
- Any anti-cancer therapy including chemotherapy, biologic or immunotherapy,
radiotherapy, etc;
- Any investigational therapy, including targeted small molecule agents.
- For CLL subjects who come off BCR antagonists (BTK inhibitors, PI3K inhibitors,
etc.) treatment, allow washout for 2 days as these subjects progress quickly
after treatment discontinuation and then remain eligible (steroids may be given
during these two days to allow disease control).
- Subjects who require immediate cytoreduction. However, subjects may receive up to two
days of steroids for symptoms of impending organ impairment and remain eligible.
- Subject has received the following medications or therapies within 7 days prior to the
first dose of study drug:
- Steroid therapy (at dosages equivalent to prednisone >20 mg/day) for
anti-neoplastic intent (except as noted in exclusion criteria #3);
- Cytochrome P450, family 3, subfamily A (CYP3A4) strong inhibitors and strong
CYP2C8 inducers/inhibitors.
- Potent CYP3A4 inducers such as rifampin, carbamazepine, phenytoin, and St. John's
wort.
- Subjects require treatment with systemic acid-reducing agents including H-2-receptor
antagonists and proton pump inhibitors with the following exceptions:
- Proton pump inhibitors should be discontinued at least 7 days prior and held
throughout the study
- If concurrent use of an H2 blocking agent is necessary, it must be administered
only between 2 and 3 hours after the dose of LP-168. If not taken during this
time, the dose of H2 blocking agents should not be taken again until 2-3 hours
after the next dose of LP-168.
- If concurrent use of a local antacid is necessary, it must be administered 2 or
more hours before and/or 2 or more hours after the dose of LP-168.
- Subject has significant screening electrocardiogram (ECG) abnormalities including. 2nd
degree AV block type II 3rd degree block, Grade 2 or higher bradycardia, and corrected
QT interval (QTc) ≥ 480ms.
- Serum amylase > 1.5 × ULN or serum lipase > 1.5 × ULN.
- Subject has any history of Richter's transformation for Phase 1a portion of the trial.
- Subjects who have undergone autologous/allogeneic hematopoietic stem cell
transplantation (HSCT) therapy within 90 days of the first dose of LP-168, or patients
on immunosuppressive therapy post-HSCT at the time of Screening, or currently with
clinically significant graft-versus-host disease (GVHD) as per treating physician
(Patients in relapse after allogeneic transplantation must be off treatment with
systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids
and/or up to 20 mg/day prednisone or equivalent systemic steroids for ongoing GVHD is
permitted.
- Subject has a history of other active malignancies other than B-cell malignancies
within the past 3 years prior to study entry, with the exception of:
- Adequately treated in situ carcinoma of the cervix uteri;
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the
skin;
- Previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent.
- Subject requires anticoagulation with Warfarin.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, (206) 335-3820, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04775745
Organization ID
LP-168-US-I01
Responsible Party
Sponsor
Study Sponsor
Newave Pharmaceutical Inc
Study Sponsor
, ,
Verification Date
October 2022