Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS/MPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL.

NCT04771572 | Recruiting Phase 1 FDA Drug

• 1 other identifier: LP-118-US-I01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase 1, multi-center, open-label study with a dose-escalation phase (Phase 1a) and a cohort expansion phase (Phase 1b), to evaluate the safety, tolerability, and PK profile of LP-118 under a once daily oral dosing schedule in up to 100 subjects.

Conditions

Non Hodgkin Lymphoma; Richter Transformation; Multiple Myeloma; T-cell-prolymphocytic Leukemia; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Myeodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelofibrosis; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Chronic Myelomonocytic Leukemia-2; Myelodysplastic Neoplasm in Blast Phase

Keywords

Hematological Malignancies; Relapsed; Refractory

Outcome Measures

Primary Outcomes (5)

• Maximum Tolerated Dose (MTD)

  If 2 out of 6 subjects in an expanded cohort experience a DLT then this dose is considered the MTD.

  At the end of cycle 1 (each cycle is 28 days)

• Recommended Phase 2 Dose (RP2D) or Optimal Biological Dose (OBD)

  The RP2D pr OBD 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, and PK data. OBD is defined as the lowest dose providing the highest rate of efficacy while being safely administered.

  At the end of cycle 1 (each cycle is 28 days)

• Pharmacokinetic (PK) profile of LP-118: Maximum Plasma Concentration (Cmax)

  At Cycle 0 Day 1, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 (28-day cycles))

• Pharmacokinetic (PK) profile of LP-118: Area Under the Curve (AUC) of LP-118

  At Cycle 0 Day 1, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 (28-day cycles)

• Pharmacokinetic (PK) profile of LP-118: Time at Maximum Concentration (Tmax) of LP-118

  At Cycle 0 Day 1, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 1 Day 16, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 (28-day cycles)

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Approximately 36 cycles (each cycle has 28 days)

• Duration of Response (DOR)

  Approximately 36 cycles (each cycle is 28 days)

• Overall Survival (OS)

  Approximately 36 cycles (each cycle is 28 days)

Study Arms (2)

Dose Escalation Phase

EXPERIMENTAL

Phase 1a dose-escalation will begin with group 1 and proceed until DLT is observed and MTD is established, or until an RP2D is established. Subjects enrolled in the dose cohorts will follow the 3+3 study design, starting with an accelerated step-up dosing schedule (with a starting dose of 20 mg, 50 mg, 100 mg once daily) until they reach the designated target dose (50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg). Once the MTD or RP2D is established for group 1, the phase 1a dose escalation can proceed for group 2. The starting dose level for group 2 will be one dose level below the MTD or RP2D established for group 1.

Drug: LP-118

Dose Expansion Phase

EXPERIMENTAL

Additional subjects will be recruited to further explore the safety, tolerability, PK, and efficacy in specific subject subgroups. One or more RP2D may be explored. Definition of these cohorts will be accomplished by protocol amendment, and in light of emerging data from Phase 1a.

Drug: LP-118

Interventions

LP-118 DRUG

novel, oral, selective treatment for hematological malignancies tested through ascending dose levels

Dose Escalation Phase; Dose Expansion Phase

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, ≥ 18 years of age at the time of Screening with the following exception as outlined below:
• For T cell and B cell ALL subjects with age between 13 - 18 years, their body weight shall be ≥ 40 kg.
• Eligible subject must have an advanced hematologic malignancy including:
• Group 1:
• Group 1a
• Relapsed or refractory low risk tumor lysis CLL/SLL subjects (ALC \< 25 x 109 cells/L and all lymph nodes \< 5 cm) who have received at least two prior therapies. Subjects may also have slowly progressed on irreversible BTK inhibitors while on treatment with these agents.
• For CLL/SLL subjects who come off BCR antagonist treatment (BTK inhibitors, P13K inhibitors, etc.) allows 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).
• Group 1b
• Morphologically confirmed diagnosis of MF in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;
• Morphologically confirmed diagnosis of MDS/MPN, excluding juvenile myelomonocytic leukemia (JMML), in accordance with WHO 2016 revised criteria, that is relapsed and/or refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;
• Chronic myelomonocytic leukemia (CMML) with \<9% blasts;
• Or atypical chronic myeloid leukemia (aCML) with Hgb \> 10g/dL, WBC count \< 50 x 109 cells/L, \<10% immature circulating cells;
• Or MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) with Hgb \> 10g/dL;
• Or myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-UC)
• CMML-2 with 10-19% blasts as defined by WHO 2016 revised criteria that is relapsed and/or refractory to prior HMA therapy;

You may not qualify if:

• A subject will not be eligible for study participation if he/she meets any of the following criteria.
• Subjects who have undergone autologous/allogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Subjects 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 malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed with the Medical Monitor with the exception below.
• Subject with breast cancer or prostate cancer on endocrine therapy with stable disease;
• Continuation of maintenance therapy in patients with adequately treated malignancy
• 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.
• Cancer with expected survival of 2 years or more or that will not confound evaluation of LP-118 treatment
• Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of LP-118, or has not recovered to ≤ Grade 2 clinically significant AEs of the previous therapy (excluding neuropathy):
• Any anti-neoplastic therapy including chemotherapy, hormonal therapy, radiotherapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy \< 20 mg/day prednisone equivalent according to institutional guidelines to treat disease associated symptoms are permitted);
• For MF subjects who come off JAK2 antagonists, allow washout for 2 days as these subject's progress quickly after treatment discontinuation and remain eligible (steroids may be given during these two days to allow disease control).
• Subjects in need of immediate cytoreduction should be excluded.
• Any investigational therapy.
• Live vaccines

Sponsors & Collaborators

• Newave Pharmaceutical Inc: lead

Study Sites (8)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45229, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Multiple Myeloma; Leukemia, Prolymphocytic, T-Cell; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic-Myeloproliferative Diseases; Primary Myelofibrosis; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Leukemia, Prolymphocytic; Leukemia, Lymphoid; Leukemia; Leukemia, T-Cell; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site

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: The study will start at lower doses (20 mg) and adopt an "accelerated titration" design for these cohorts. Once the safety of the 20 mg dose level is established, we will continue dose escalation using a classic "3+3" design to establish DLT, MTD, and RP2D, starting also with an accelerated step-up dosing schedule.

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 25, 2021
• Study Start: May 8, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (8)