A Phase 1 Clinical Trail of NTQ2494 Tablets in Patients With Advanced Hematological Malignancies

Official title

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Preliminary Efficacy of NTQ2494 Tablets in Patients With Advanced Hematological Malignancies

Overview

NTQ2494 tablet, an anti-tumor molecular targeted drug, is an AXL kinase inhibitor. The objectives were to evaluate the safety and tolerability, PK characteristics and preliminary efficacy of NTQ2494 tablets in patients with advanced hematological malignancies.

Interventions

• Drug NTQ2494 tablet
  Drug: NTQ2494 tablet Part 1: Dose escalation, single and multiple doses of NTQ2494 with dose modifications based on tolerability criteria. For each dose level, a single dose of NTQ2494 tablets will be first administered orally, then continuous 28-day treatment will start (per cycle). Part 2: Dose expansion, recommended doses from Part 1. For each dose level, multiple doses of NTQ2494 tablets will be administered as 28-day treatment (per cycle).

Primary outcome measures

• Maximum tolerance dose (MTD) and dose limiting toxicity (DLT) [Time frame: 30 days]

Secondary outcome measures (12)

• Cmax of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• AUC0-t of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• AUC0-∞ of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Tmax of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• t1/2z of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Vz/F of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• CLz/F of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• λz of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• MRT0-t of single dose [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Rac of AUC and Cmax of first 28 days of multiple doses [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• DF of AUC and Cmax of first 28 days of multiple doses [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Css,max of first 28 days of multiple doses [Time frame: At the end of Cycle 1 (each cycle is 28 days)]

Eligibility criteria

Inclusion criteria

• ≥18 years in age, male or female.
• Relapsed/refractory AML patients.
• ECOG performance status score is 0 to 2.
• Life expectancy of at least 3 months.
• Adequate bone marrow and good organ function.
• Ability to understand the purpose and risks of the study and the willingness to sign a written informed consent document.

Exclusion criteria

• Receiving anticancer therapy including immunotherapy, targeted therapy, endocrine therapy, radiotherapy and chemotherapy within 2 weeks or 5 half-lives (whichever is longer) prior to starting study treatment.
• Receiving any other investigational agents within 4 weeks prior to starting study treatment.
• Having major surgery within 4 weeks prior to starting study treatment, or intended to undergo surgery during the trail.
• AML with any of the following: 1) acute promyelocytic leukemia; 2) AML with blast crisis of chronic myelogenous leukemia; 3) central nervous system leukemia.
• Prior or current other malignancy (except cured noninvasive basal cell or squamous cell skin cancer and/or other cured carcinoma in situ; except for other malignancies that have achieved clinical cure for > 5 years and have not recurred within 5 years).History of severe cardiovascular or cerebrovascular disease.
• Use of strong inhibitors or strong inducers of CYP3A4 or P-gp within 7 days prior to starting study treatment.
• Receiving (attenuated) live vaccines within 4 weeks prior to starting study treatment and/or planning to receive (attenuated) live vaccines during the trial.
• With unresolved clinically significant non-hematological toxicities from prior AML therapy (chemotherapy, targeted therapy, immunotherapy, radiotherapy and surgery), defined as any grade 2 or higher grade (CTCAE v5.0), alopecia and other events that are tolerable as judged by the investigator.
• Patients who have received previous allogeneic hematopoietic stem cell transplantation; or received autologous hematopoietic stem cell transplantation within 3 months prior to starting study treatment.
• Unable to swallow oral tablets, or other conditions seriously affecting gastrointestinal absorption judged by the investigator.
• Patients with uncontrolled infections unsuitable for the trail judged by the investigator.
• Known infection with hepatitis B, hepatitis C, HIV or Syphilis.
• Known alcohol or drug dependence.
• Patients with mental disorders or poor compliance.
• Patients with a previous history of severe allergy to any drug or food.
• Lactating or pregnant female, and females or males (or partners) who plan to pregnant and do not agree to use adequate contraception for the duration of the trail and up to 3 months after completion of the last study treatment.
• Other reasons judged by the investigator that the patients unsuitable for the trail.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Hematology Hospital of the Chinese Academy of Medical Sciences — Tianjin

Identifiers

NCT: NCT06049667 · NTQ2494-23101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗