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

A Phase Ib Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of TQB3909 Tablets Combined With TQB3702 Tablets in Hematologic Malignancy Subjects.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hematologic Malignancy
• Intervention / Treatment: Drug: TQB3909 tablets; Drug: TQB3702 tablets

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yanyan Liu, Doctor; Phone Number: +86-13838176375; Email: yyliu@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
      • Contact: Yanyan Liu, Doctor; Phone Number: +86-13838176375; Email: yyliu@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQB3909 tablets+ TQB3702 tablets; TQB3909 tablets combined with TQB3702 tablets, administered orally, 28 days as a treatment cycle.	Drug: TQB3909 tablets; TQB3909 is a protein inhibitor.; Drug: TQB3702 tablets; TQB3702 is a kinase inhibitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limited toxicity (DLT)	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.	Baseline up to 104 weeks
Adverse events (AE)	The occurrence of all adverse events (AE).	Baseline up to 104 weeks
Serious adverse events (SAE)	The occurrence of all serious adverse events (SAE).	Baseline up to 104 weeks
Clinical laboratory abnormalities	Incidence of participants with abnormal clinical laboratory test results.	Baseline up to 104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first	Baseline up to 104 weeks
Complete remission rate (CRR)/ Complete remission with incomplete bone marrow recovery rate (CRi)	The proportion of patients with tumor hat have a complete response or complete remission with incomplete bone marrow recovery after treatment.	Baseline up to 104 weeks
Objective Response Rate (ORR)	The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period.	Baseline up to 104 weeks
Undetectable measurable residual disease (U-MRD) ratio of peripheral blood and/or bone marrow	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.	Baseline up to 104 weeks
Duration of complete remission / complete remission with incomplete bone marrow recovery	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).	Baseline up to 104 weeks
Duration of Response (DOR)	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).	Baseline up to 104 weeks
Time to complete remission	The time from beginning the treatment to the first achieving complete remission/ complete remission with incomplete bone marrow recovery.	Baseline up to 104 weeks
Time to remission (TTR)	Time from the beginning of treatment to the first recording of remission (PR or better remission), only the remission population will be analyzed.	Baseline up to 104 weeks
Overall Survival (OS)	The time from start of study treatment to date of death due to any cause.	Baseline up to 104 weeks
2 years' PFS rate	The proportion of patients with progression free survival in 2 years.	Baseline up to 104 weeks
2 years' OS rate	The proportion of patients achieving overall survival in two years.	Baseline up to 104 weeks
Time to reach the maximum plasma concentration (Tmax)	Time to reach the maximum plasma concentration after dose	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.
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)	Cmax is the maximum plasma concentration of TQB3909 and TQB3702	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.
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)	Cmin is the minimum plasma concentration of TQB3909 and TQB3702.	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.

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Estimated): January 18, 2024

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: TQB3909-TQB3702-Ib -01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No