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COMPLETEDPHASE1

Dose-Escalation Study of Oral Administration of LP-108 as Monotherapy and in Combination With Azacitidine in Patients With Relapsed or Refractory MDS, CMML, or AML

A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-108 as Monotherapy and in Combination With Azacitidine in Subjects With Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)

NCT04139434•Newave Pharmaceutical Inc

View on ClinicalTrials.gov

Summary

A Phase 1, Multicenter, Open-label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Clinical Activity of Orally Administered LP-108 as Monotherapy and in Combination with Azacitidine in Subjects with Relapsed or Refractory Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)

Detailed Description

The primary objectives are to assess the safety and tolerability profile, determine the maximum tolerated dose (MTD), and/or the recommended Phase 2 dose (RP2D) of LP-108 administered daily as a single agent dosed orally and in combination with azacitidine at 75 mg/m2 in adult subjects with relapsed/refractory MDS/CMML/AML; to characterize the pharmacokinetics (PK) profile of LP-108 as monotherapy and in combination with azacitidine in adult subjects with relapsed/refractory MDS/CMML/AML. Secondary objectives are to evaluate preliminary efficacy regarding the effect of LP-108 (monotherapy or combination therapy) on ORR for AML, MDS, CMML, PFS, DOR, and OS

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•A subject will be eligible for study participation if the subject meets the following criteria:
•Eligible subject must have an advanced hematologic malignancy including:
•* MDS with refractory anemia with excess blasts (RAEB; subtype RAEB-1 or RAEB-2) as defined by World Health Organization (WHO) 2016 revised criteria and/or MDS with high- or very high-risk (risk score \> 4.5) per the Revised International Prognostic Scoring System (IPSS-R) (Greenberg et al. 2012) that is relapsed or refractory to prior therapy for MDS, or the subject is intolerant to established therapy known to provide clinical benefit for their condition in the opinion of the Investigator; Or relapsed and/or refractory MDS subjects in whom the Investigators feel would benefit from Arm 2.
•* Relapsed and/or primary refractory AML as defined by WHO 2016 revised criteria; Or frontline older and/or unfit AML subjects in whom the Investigators feel would benefit from Arm 2.
•* CMML (with ≥ 5% blasts in bone marrow) as defined by WHO 2016 revised criteria that is relapsed and/or refractory and that, in the opinion of the Investigator, requires treatment or that has exhausted treatment options that would be considered standard of care.
•* Subject's prior therapies may include other BCL2 inhibitors and other HMA agents for Arm 2.
•Blast count ≤ 30 × 10\^9 cells/L at the time of initiating investigational therapy (hydroxyurea is allowed to control blast count prior to and during therapy).
•Subject must have adequate coagulation, renal, and hepatic function.
•* Activated partial thromboplastin time and prothrombin time not to exceed 1.5 × the upper limit of normal (ULN);
•* Calculated creatinine clearance (Cr Cl) ≥ 30 mL/min using 24-hour CrCl OR Cockcroft-Gault formula (using actual body weight)
+3 more criteria

Exclusion Criteria

•A subject will not be eligible for study participation if he/she meets any of the following criteria.
•Subjects with a diagnosis of promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA) or non-PML-RARA rearranged acute promyelocytic leukemia (APL).
•Subjects who have undergone hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of LP-108, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or with clinically significant graft-versus-host disease (GVHD). (Subjects in relapse after allogeneic transplantation must be off calcineurin inhibitors 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 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) of the previous therapy:
•* Any anti-cancer therapy including chemotherapy, hormonal therapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy \< 20 mg/day prednisone equivalent for \< 14 days at time of study treatment and hydroxyurea cytoreduction therapy according to institutional guidelines to treat disease associated symptoms are permitted).
•* Any investigational therapy.
•* There is 28-day washout period required for subject who have had prior CAR-T treatment if there is no evidence of cytokine release syndrome (CRS) or other adverse events related to the CAR-T treatment per discussion with the Medical Monitor.
•Subject has received the following medications or therapies within 7 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug:
•* Cytochrome P450, family 3, subfamily A (CYP3A4) strong inhibitors (see Appendix 10 for strong CYP3A4 inhibitors). In Phase 1b of this trial, the criterion regarding CYP3A4 strong inhibitors will be removed at time of amendment of the trial when Phase 1b is to be initiated. The amendment will include recommendations on concomitant dosing of LP-108 and strong CYP3A4 inhibitors such as azole antifungal agents, PK monitoring for the initial weeks on study, as well as closer safety monitoring for subjects.
•* Strong CYP3A4 inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.
+18 more criteria

Locations (7)

University of Michigan

Ann Arbor, Michigan, United States

University of Cincinnati

Cincinnati, Ohio, United States

Ohio State Comprehensive Cancer Center

Columbus, Ohio, United States

MD Anderson Cancer Center

Huston, Texas, United States

Institut Català d'oncologia - ICO Badalona

Badalona, Barcelona, Spain

Hospital San Pedro de Alcántara

Cáceres, Cáceres, Spain

Instituto de Investigación Sanitaria La Fe

Valencia, Valencia, Spain

Key Dates

Start Date

July 6, 2020

Primary Completion Date

December 19, 2025

Completion Date

December 19, 2025

Last Updated

January 23, 2026

Enrollment

ACTUAL participants

Conditions

AML/MDSCMMLRelapseRefractory Acute Lymphoblastic LeukemiaRelapse LeukemiaRelapsed Adult AML

Interventions

LP-108

DRUG

LP-108 and azacitidine

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 23, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Dose-Escalation Study of Oral Administration of LP-108 as Monotherapy and in Combination With Azacitidine in Patients With Relapsed or Refractory MDS, CMML, or AML

Inclusion Criteria

Exclusion Criteria

A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Daratumumab, and Dexamethasone Plus Pomalidomide in Multiple Myeloma

U69-CART-Cells For R/R T-ALL

A Study to Evaluate MK-1045 (CN201) in Participants With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma (MK-1045-001/CN201-101)

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