Clinical trial NCT06211751: A Clinical Trial of TQB3909 Tablets Combined With TQB3702 Tablets in Patients With Hematologic Malignancy
Official title: A Phase Ib Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of TQB3909 Tablets Combined With TQB3702 Tablets in Hematologic Malignancy Subjects.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Hematologic Malignancy
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-18
Enrollment: 208
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 is an open, multi-cohort 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 safety and preliminary efficacy of TQB3909 tablets combined with TQB3702 tablets in hematologic malignancy subjects.


Eligibility criteria: Inclusion Criteria:

* Subjects voluntarily joined the study, signed informed consent form, and with good compliance.
* ≥ 18 years old, ≤75 years old (when signing informed consent form); Eastern Cooperative Oncology Group (ECOG) physical status: 0-2; at least 3 months expected survival period.
* Subject population:

  1. Dose escalation stage: non-Hodgkin's B-cell lymphoma;
  2. Dose expansion stage: non-Hodgkin's lymphoma, etc.
* At least 1 lesion / measurable disease 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 the completion of the study; 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 the completion of the study.

Exclusion Criteria:

* Patients has occured or is currently having other malignant tumors within 5 years. The following two conditions can be included: other malignant tumors treated with a single operation to achieved 5 consecutive years of disease free survival (DFS). Cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basal membrane)\] and papillary thyroid carcinoma.
* Burkitt lymphoma, lymphoblastic lymphoma/leukemia, etc.
* For cohort A and cohort B: Richter transformation occured.
* Subjects with central nervous system (CNS) aggression;
* Previously received allogeneic hematopoietic stem cell transplantation;
* For Cohort B/D/E: Received autologous hematopoietic stem cell transplantation within 3 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 ≥CTCAE grade 1 due to any previous treatment, excluding alopecia and fatigue;
* Major surgical treatment, open biopsy, and significant traumatic injury received within 28 days before the start of study treatment.
* Having active or uncontrolled primary autoimmune hemocytopenia, including autoimmune hemolytic anemia (AIHA), primary immune thrombocytopenia (ITP), etc.
* Patients with evidence or history of bleeding constitution; Or any bleeding event (such as gastrointestinal bleeding) greater than or equal to CTCAE level 3 within 4 weeks before the first dose;
* Subjects who had an arteriovenous thrombosis event within 6 months.
* Subjects who had a history of psychotropic substance abuse and are unable to abstain or have mental disorders;
* Subjects with any severe and/or uncontrolled disease.
* Within one weeks before the first dose, the subjects had received proprietary Chinese medicines with anti-tumor indications specified in the National Medical Products Administration (NMPA) approved drug instructions;
* 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 dose;
* 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: Dose limited toxicity (DLT)
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: Clinical laboratory abnormalities
timeFrame: Baseline up to 104 weeks
Secondary outcomes:
measure: Complete remission rate (CRR)/ Complete remission with incomplete bone marrow recovery rate (CRi)
timeFrame: Baseline up to 104 weeks
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to 104 weeks
measure: Undetectable measurable residual disease (U-MRD) ratio of peripheral blood and/or bone marrow
timeFrame: Baseline up to 104 weeks
measure: Duration of complete remission / complete remission with incomplete bone marrow recovery
timeFrame: Baseline up to 104 weeks
measure: Duration of Response (DOR)
timeFrame: Baseline up to 104 weeks
measure: Time to complete remission
timeFrame: Baseline up to 104 weeks
measure: Time to remission (TTR)
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: 2 years' PFS rate
timeFrame: Baseline up to 104 weeks
measure: 2 years' OS rate
timeFrame: Baseline up to 104 weeks
measure: Time to reach the maximum plasma concentration (Tmax)
timeFrame: Before the first dose of TQB3702 tablet and target dose of TQB3909 tablet. 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after the first target dose of TQB3909 tablet. The 4th /11th day before dosing with target dose of TQB3909 tablet.
measure: Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)
timeFrame: Before the first dose of TQB3702 tablet and target dose of TQB3909 tablet. 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after the first target dose of TQB3909 tablet. The 4th /11th day before dosing with target dose of TQB3909 tablet.
measure: Minimum steady-state plasma drug concentration during a dosage interval (Css-min)
timeFrame: Before the first dose of TQB3702 tablet and target dose of TQB3909 tablet. 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours after the first target dose of TQB3909 tablet. The 4th /11th day before dosing with target dose of TQB3909 tablet.
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
Study officials:
References: