A Clinical Trial of TQB3909 Tablets Combined With TQB3702 Tablets in Patients With Hematologic Malignancy

Phase 1

Not yet recruiting

• Conditions: Hematologic Malignancy
• Interventions: Drug: TQB3909 tablets; Drug: TQB3702 tablets

• Registration Number: NCT06211751
• Lead Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-01
• Study Start: 2024-01
• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-09
• Last Update Submitted: 2024-01-09
• Study First Posted: 2024-01-18
• Last Update Posted: 2024-01-18
• Primary Completion: 2025-12
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 208

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TQB3909 tablets+ TQB3702 tablets	TQB3909 tablets	TQB3909 tablets combined with TQB3702 tablets, administered orally, 28 days as a treatment cycle.
TQB3909 tablets+ TQB3702 tablets	TQB3702 tablets	TQB3909 tablets combined with TQB3702 tablets, administered orally, 28 days as a treatment cycle.

Primary Outcome Measures

Name	Time	Method
Dose limited toxicity (DLT)	Baseline up to 104 weeks	DLT will be defined as toxicities that meet pre-defined severity criteria (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), and assessed as having a suspected relationship to study drug.
Serious adverse events (SAE)	Baseline up to 104 weeks	The occurrence of all serious adverse events (SAE).
Clinical laboratory abnormalities	Baseline up to 104 weeks	Incidence of participants with abnormal clinical laboratory test results.
Adverse events (AE)	Baseline up to 104 weeks	The occurrence of all adverse events (AE).

Secondary Outcome Measures

Name	Time	Method
2 years' OS rate	Baseline up to 104 weeks	The proportion of patients achieving overall survival in two years.
Complete remission rate (CRR)/ Complete remission with incomplete bone marrow recovery rate (CRi)	Baseline up to 104 weeks	The proportion of patients with tumor hat have a complete response or complete remission with incomplete bone marrow recovery after treatment.
Duration of Response (DOR)	Baseline up to 104 weeks	For all subjects whose best response was partial response (PR), Complete Response (CR), the time from the date of first achieving PR, CR to the date of first definite disease progression or death from any cause (whichever occurs first).
Time to reach the maximum plasma concentration (Tmax)	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.	Time to reach the maximum plasma concentration after dose
Progression Free Survival (PFS)	Baseline up to 104 weeks	The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first
Objective Response Rate (ORR)	Baseline up to 104 weeks	The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period.
Duration of complete remission / complete remission with incomplete bone marrow recovery	Baseline up to 104 weeks	The time from the date of first achieving CR or CRi to the date of first definite disease progression or death from any cause (whichever occurs first).
Time to complete remission	Baseline up to 104 weeks	The time from beginning the treatment to the first achieving complete remission/ complete remission with incomplete bone marrow recovery.
Overall Survival (OS)	Baseline up to 104 weeks	The time from start of study treatment to date of death due to any cause.
Undetectable measurable residual disease (U-MRD) ratio of peripheral blood and/or bone marrow	Baseline up to 104 weeks	Refers to the undetected residual lesions. Flow cytometry was used to detect less than 1 Chronic Lymphocytic Leukemia (CLL) cell (less than 10-4) in 10,000 white blood cells in peripheral blood and/or bone marrow.
Time to remission (TTR)	Baseline up to 104 weeks	Time from the beginning of treatment to the first recording of remission (PR or better remission), only the remission population will be analyzed.
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)	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.	Cmax is the maximum plasma concentration of TQB3909 and TQB3702
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)	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.	Cmin is the minimum plasma concentration of TQB3909 and TQB3702.
2 years' PFS rate	Baseline up to 104 weeks	The proportion of patients with progression free survival in 2 years.

Trial Locations

Locations (1)

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China