Assessing the safety and effectiveness of LP-108 with azacitidine for blood cancers

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LP-108, a BCL-2 Inhibitor, Combined With Azacitidine In Subjects With AML, MDS, CMML

This study is testing a new combination of LP-108 and azacitidine to see if it helps people with blood cancers like acute myeloid leukemia, myelodysplastic syndromes, or chronic myelomonocytic leukemia feel better and stay safe during treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 198 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 3 sites (Nanchang and 2 other locations)
• Trial ID: NCT05641259 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial evaluates the safety, tolerability, and pharmacokinetics of LP-108, a BCL-2 inhibitor, in combination with azacitidine for patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or chronic myelomonocytic leukemia (CMML). The study involves a multicenter, open-label design with dose-escalation and expansion phases to determine the recommended Phase 2 dose and to assess preliminary efficacy. Participants will undergo screening, treatment, and regular blood and bone marrow tests to monitor safety and response to the treatment. The trial aims to treat participants until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include adults with relapsed or refractory AML, MDS, or CMML who are ineligible for standard chemotherapy.

Not a fit: Patients with low performance status or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with difficult-to-treat blood cancers.

How similar studies have performed: Other studies have shown promise with BCL-2 inhibitors in hematological malignancies, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Subject must has a diagnosis of one of the following: relapsed or refractory (R/R) or untreated ineligible for treatment with a standard induction chemotherapy acute myeloid leukemia (AML) ; R/R myelodysplastic syndrome(MDS) or untreated MDS with excess blasts defined as ≥ 5% blasts in either bone marrow or blood or with high risk (high and very high-risk groups according to IPSS-R) ;CMML-1 or 2 by WHO, no requirements for prior therapy.
* ECOG performance status ≤ 2.
* Estimated survival ≥ 12 weeks.
* Baseline white blood cell count (WBC) ≤ 25 x 109/L.
* Subject must has adequate organ function as defined below: Aspartate transaminase (AST) and alanine transaminase (ALT)≤3 x ULN; Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin); adequate renal function as demonstrated by a creatinine clearance ≤1.5 x ULN ; calculated by the Cockcroft Gault formula; APTT ≤ 1.5 x ULN, INR ≤ 1.5 x ULN.
* Prior treatment-related toxicities must be grade 1 or baseline except for alopecia.
* If subject is sexually active, he/she must agree to carry out birth control throughout the study and 90 days after the last dose of LP-108. Subject must agree to have a negative serum β-HCG test result within 7 days prior to study drug.
* Subject must voluntarily sign and date an informed consent.

Exclusion Criteria:

* Subject is allergic to LP-108, Azacitidine or excipients, or with poor tolerance to Azacitidine.
* Subject has received prior therapy with a BH3 mimetic.
* Subject has acute promyelocytic leukemia.
* Subject has t(9;22) karyotype abnormality or positive BCR/ABL1 fusion gene.
* Subject has known and active CNS involvement.
* Subject has myeloid sarcoma but no bone marrow involvement.
* Subject has Acute unidentified leukemia.
* Subject has treatment related MDS or AML.
* Subject has AML/MDS/CMML with myelofibrosis ≥ grade 2.
* Subject has received allogeneic Hematopoietic Stem Cell Transplantation (HSCT) or autologous HSCT within 3 months prior to the first dose of study drug.
* Subject must be at least 4 weeks from antitumor therapy, major surgery, radiation therapy, or participation in other investigational trials.
* Subject has received a strong and/or moderate CYP3A inhibitor or inducer, P-gp inhibitor or CYP2C8 substrate within 14 days prior to the initiation of study treatment.
* Subject has received drugs with a potential to cause prolonged QT intervals or torsade de pointes.
* Administration or consumption of any of the following within 3 days prior to the first dose of study drug: Grapefruit or grapefruit products; Seville oranges (including marmalade containing Seville oranges); Star fruit.
* Subject has known malignancy within 3 years prior to the first dose of study drug, with the exception of: Adequately treated basal skin cancers, in situ carcinoma of the cervix uteri or breast, localized squamous cell carcinoma.
* Subject has serious and/or uncontrolled systemic diseases, in the opinion of the investigator, the subject is inappropriate for enrollment into this study (serious active infection with grade ≥ 2(based on CTCAE), high blood pressure that cannot be controlled by medication, diabetes, unstable angina, congestive heart failure, Respiratory diseases requiring continuous oxygen intake, severe vascular embolism, uncontrolled massive bleeding or bleeding from vital organs, severe liver, kidney or metabolic diseases, such as cirrhosis, kidney failure, etc.).
* Subject has myocardial infarction or stroke within 6 months prior to the first dose of study drug.
* Subject has a cardiac history including the following: History of CHF requiring treatment or Ejection Fraction \<50% or a cardiovascular disability status of New York Heart Association.
* Subject has uncontrolled and/or active systemic infection (viral, bacterial or fungal).
* Subject has difficulty to swallow pills or has conditions that affect drug absorption or pharmacokinetics.
* Strong and/or moderate CYP3A inhibitor or inducer and CYP2C8 substrate cannot be discontinued during the study.
* Vaccination with live, attenuated vaccines ≤4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study or 4 weeks after the last dose of study drug.
* Subject has an autoimmune disease that requires immunosuppressive therapy In the opinion of the investigator, the subject is inappropriate for enrollment into this study.

Where this trial is running

Nanchang and 2 other locations

• The First Affiliated Hospital of Nanchang University — Nanchang, China (Recruiting)
• First Affiliated Hospital of Soochow University — Suzhou, China (Recruiting)
• Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital — Zhengzhou, China (Recruiting)

Study contacts

• Principal investigator: Xudong Wei, PhD — Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital
• Study coordinator: Yue Shen, PhD

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia