Clinical trial NCT05610202: Tolerability and Pharmacokinetics Study of TQB3702 Tablets in Hematologic Tumor Subjects
Official title: Phase I Clinical Trial of Tolerability and Pharmacokinetics of TQB3702 Tablets in Hematologic Tumor Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hematologic Malignancy
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-11-09
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This project is an open, dose escalation and expansion phase I clinical study. The first phase is a dose escalation study, and the second phase is a dose expansion study based on the Maximum tolerated dose (MTD) / Recommended Phase II Dose (RP2D) obtained in the first phase. The purpose is to evaluate the tolerability and preliminary efficacy of TQB3702 tablets in hematological tumor subjects.


Eligibility criteria: Inclusion Criteria:

* Subjects voluntarily joined the study, signed informed consent form, and with good compliance.
* ≥18 years old and ≤ 80 years old; Eastern Cooperative Oncology Group (ECOG) physical status: 0-2; at least 3 months expected survival period.
* Clearly diagnosed recurrent / refractory hematological tumors that meet the WHO definition;
* At least 1 measurable lesion for efficacy evaluation.
* The function of main organs is normal.
* Female patients of childbearing age should agree to use contraceptive measures during the study period and for at least 6 months after study is stopped; a negative serum pregnancy test within 7 days prior to study enrollment and must be non-lactating subjects; male patients should agree to use contraception during the study period and for at least 6 months after study is stopped.

Exclusion Criteria:

* Patients has had or is currently having other malignant tumors within 3 years. The following two conditions can be included in the group: other malignant tumors treated with a single operation to achieved 5 consecutive years of disease free survival (DFS)s. Cured cervical carcinoma in situ, non-melanoma skin cancer, nasopharyngeal carcinoma and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\].
* Subjects with central nervous system aggression (CNS);
* Received allogeneic hematopoietic stem cell transplantation (allo-HSCT) or had active graft-versus-host disease (GVHD) requiring immunosuppressive therapy within 12 months before the first dose;
* Multiple factors that affect the absorption of oral medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction);
* Unrelieved toxicity of ≥CTC AE grade 1 due to any previous treatment, excluding alopecia and fatigue;
* Major surgical treatment, open biopsy, and significant traumatic injury were received within 28 days before the start of study treatment.
* The presence of active or uncontrolled primary autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP);
* Patients with evidence or history of bleeding constitution; Or any bleeding event (such as gastrointestinal bleeding) greater than or equal to CTC AE level 3 within 4 weeks before the first medication;
* Subjects had an arteriovenous thrombosis event within 6 months.
* Subjects have history of psychotropic substance abuse and are unable to abstain or have mental disorders;
* Subjects with any severe and/or uncontrolled disease.
* Within 2 weeks before the first treatment, the subjects had received proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions;
* Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage (investigator judgment);
* Study treatment related: subjects received live or mRNA vaccines within 4 weeks before the first treatment or were scheduled to receive live or mRNA vaccines during the study;
* Participated in clinical trials of other antitumor drugs within 4 weeks before the first treatment;
* According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are considered unsuitable for enrollment for other reasons.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Baseline up to 104 weeks
measure: Dose limited toxicity (DLT)
timeFrame: Baseline up to 104 weeks
measure: Recommended Phase II Dose (RP2D)
timeFrame: Baseline up to 104 weeks
Secondary outcomes:
measure: Time to Reach the Maximum Plasma Concentration (Tmax)-single dose
timeFrame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
measure: Time to Reach the Maximum Plasma Concentration (Tmax)-multiple dose
timeFrame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
measure: Maximum plasma concentration (Cmax)-Single dose
timeFrame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
measure: Maximum plasma concentration (Cmax)-Multiple dose
timeFrame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
measure: Elimination half-life (t1/2)-Single dose
timeFrame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72 hours after administration.
measure: Elimination half-life (t1/2)-Multiple dose
timeFrame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
measure: Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Single dose
timeFrame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
measure: Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Multiple dose
timeFrame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
measure: Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Single dose
timeFrame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
measure: Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Multiple dose
timeFrame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
measure: steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-single dose
timeFrame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
measure: steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-multiple dose
timeFrame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
measure: Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-Single dose
timeFrame: before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
measure: Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-multiple dose
timeFrame: before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to 104 weeks
measure: Complete Remission Rate (CRR)
timeFrame: Baseline up to 104 weeks
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to 104 weeks
measure: Duration of Response (DOR)
timeFrame: Baseline up to 104 weeks
measure: Progression Free Survival (PFS)
timeFrame: Baseline up to 104 weeks
measure: Overall Survival (OS)
timeFrame: Baseline up to 104 weeks
measure: Adverse events (AE)
timeFrame: Baseline up to 104 weeks
measure: Serious adverse events (SAE)
timeFrame: Baseline up to 104 weeks
measure: Bruton's tyrosine kinase (BTK) occupancy
timeFrame: Baseline up to 104 weeks
Other outcomes:
Locations:
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Jinan
country: China
facility: The Cancer Hospital Affiliated to Shandong First Medical University
state: Shandong
Study officials:
References: