Study of Oral Administration of LP-168 in Patients With Relapsed or Refractory B-cell Malignancies.

NCT04775745 | Recruiting Phase 1 FDA Drug

• 1 other identifier: LP-168-US-I01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

CLL/SLL; Waldenstrom Macroglobulinemia; Follicular Lymphoma; Diffuse Large B Cell Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Hairy Cell Leukemia

Outcome Measures

Primary Outcomes (5)

• Maximum Tolerated Dose (MTD)

  When more than 1 DLT occurs in ≤ 6 subjects in a dosing cohort, dose escalation will be stopped and this dose level will be identified as the non-tolerated dose. Doses between the non-tolerated dose and the preceding lower dose, where ≤ 1 DLT occurred, may be explored to more precisely define the MTD.

  Up to 24 months, each cycle is 28 days

• Recommended Phase 2 dose (RP2D)

  The RP2D may be as high as the MTD or a lower dose and will be selected in discussion with the Investigators and the Sponsor based on longer term safety data, preliminary efficacy data, and PK data.

  Up to 24 months, each cycle is 28 days

• Pharmacokinetic (PK) profile of LP-168

  Maximum Plasma Concentration \[Cmax\]

  At Cycle 1: Day 1, Day 2, Day 8, Day 9, Day 15, Day 22, Day 28; At Cycle 3: Day 28; At Cycle 6 Day 28; (each cycle is 28 days)

• Pharmacokinetic (PK) profile of LP-168

  Area Under the Curve \[AUC\]

  At Cycle 1: Day 1, Day 2, Day 8, Day 9, Day 15, Day 22, Day 28; At Cycle 3: Day 28; At Cycle 6 Day 28; (each cycle is 28 days

• Pharmacokinetic (PK) profile of LP-168

  Time at Maximum Concentration \[Tmax\]

  At Cycle 1: Day 1, Day 2, Day 8, Day 9, Day 15, Day 22, Day 28; At Cycle 3: Day 28; At Cycle 6 Day 28; (each cycle is 28 days

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Up to 24 months, each cycle is 28 days

• Objective Response Rate (ORR)

  Up to 24 months, each cycle is 28 days

• Duration of Response (DOR)

  Up to 24 months, each cycle is 28 days

Study Arms (2)

Dose Escalation Phase

EXPERIMENTAL

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.

Drug: LP-168

Dose Expansion Phase

EXPERIMENTAL

Additional subjects will be recruited to further explore the safety, tolerability, PK, and efficacy in specific subject subgroups.

Drug: LP-168

Interventions

LP-168 DRUG

For the dose escalation phase, LP-168 will be given once or twice daily at the following dose levels:100 mg QD,150 mg QD, 100 mg BID, 300 mg QD, 150 mg BID, 450 mg QD, 225 mg BID, 600 mg QD, 800 mg QD, and 1000 mg QD.

Dose Escalation Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Newave Pharmaceutical Inc: lead

Study Sites (4)

Duke Univerisity

Durham, North Carolina, 27708, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45221, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Hairy Cell

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Leukemia

Central Study Contacts

Anna Chen, MD, PhD

CONTACT

(206) 335-3820; yu@newavepharma.com

Stephen Anthony, DO

CONTACT

s.anthony@newavepharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A classic "3+3" design will be used to establish the dose-limiting toxicity (DLT), MTD, and RP2D. 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 (a "Cycle"), starting at a dose of 100 mg/day. Once all subjects in a given cohort have reached Cycle 1 Day 28, these data will be reviewed by the Safety Review Committee (SRC) for decisions on dose escalation for a new dose cohort. Subjects will receive once-daily or twice-daily oral dose of LP-168 until disease progression, unacceptable toxicity, or a clinical observation satisfying another criterion for withdrawal from treatment is noted.

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 1, 2021
• Study Start: July 19, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)