Clinical Study to Evaluate the Tolerability and Pharmacokinetics of TQB2916 Injection in Patients With Advanced Malignant Tumors

Advanced Tumors Clinical Trial

Official title:

Phase I Clinical Study to Evaluate the Tolerability and Pharmacokinetics of TQB2916 Injection in Patients With Advanced Malignant Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05213767
• Other study ID #: TQB2916- I -01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: February 2022
• Est. completion date: July 2023

Study information

• Verified date: January 2022
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Yi Ba, Doctor
• Phone: 18622221230
• Email: bayi[@]tjmuch.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 safety, tolerability, and pharmacokinetic characteristics of TQB2916 injection in patients with advanced tumors, and to initially evaluate the antitumor efficacy of TQB2916 injection.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 190
• Est. completion date: July 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 1 Subjects with advanced malignant tumors clearly diagnosed by pathology and / or cytology, lack of conventional effective treatment methods, failure or relapse after treatment.

• 2 18-75 years old; Eastern Cooperative Oncology Group (ECOG) physical status: 0-1; at least 3 months expected survival period.

• 3 The function of main organs is normal.

• 4 Subjects must need to adopt effective methods of contraception.

• 5 Subjects voluntarily joined the study, signed informed consent form, and with good compliance.

Exclusion Criteria:

• 1 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 R0 resection without recurrence and metastasis. 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)].

• 2 The toxicity of previous antitumor treatment is not recovered to = grade 1 (Common Terminology Criteria for Adverse Events (CTCAE) 5.0).

• 3 Received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before treatment.

• 4 Subjects had an arteriovenous thrombosis event within 6 months.

• 5 Subjects occurred Evans syndrome within 3 months.

• 6 History of drug abuse, alcohol or drug abuse or mental disorder.

• 7 Subjects who suffered from Active tuberculosis within 1 year.

• 8 The subjects had any history of bleeding or coagulopathy.

• 9 Cirrhosis, active hepatitis.

• 10 The subjects was diagnosed with renal failure and required hemodialysis or peritoneal dialysis.

• 11 History of immunodeficiency, including positive human immunodeficiency virus (HIV) test or other acquired, congenital immunodeficiency disease, or history of organ transplantation.

• 12 Subjects who have epilepsy and require treatment.

• 13 Received the treatment of proprietary Chinese medicines with anti-tumor indications clearly stated in the National Medical Products Administration (NMPA) approved drug instructions within 2 weeks of starting treatment.

• 14 The symptoms of subjects with known central nervous system metastasis, spinal cord compression, meningeal metastasis, or leptomeningeal disease.

• 15 Vaccination history of live attenuated vaccine before 28 days of starting treatment, or planned vaccination of live attenuated vaccine during the study period.

• 16 History of severe allergy to macromolecule drugs or known components of TQB2916 injection.

• 17 Receiving any other investigational agent within 4 weeks before first dose.

• 18 According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subject or affect the completion of the study.

Related Conditions & MeSH terms

• Advanced Tumors
• Neoplasms

Intervention

Drug:
• TQB2916 injection
TQB2916 injection is a kind of Tumor necrosis factor receptor superfamily member 5 (CD40) agonist, which is a humanized immunoglobulinG2 (IgG2) monoclonal antibody targeting CD40. This product can bind to CD40 on target cells to activate downstream signaling pathways and generate anti-tumor immune responses. At the same time, it can promote the apoptosis of B-cell lymphoma Ramos cells.

Locations

Country	Name	City	State
China	Tianjin Cancer Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)	To evaluate MTD of TQB2916 injection in patients with advanced solid tumors	Baseline up to 52 weeks
Primary	Dose limited toxicity (DLT)	To evaluate DLT of TQB2916 injection in Chinese adult patients with advanced solid tumors	Baseline up to 52 weeks
Primary	Recommended Phase II Dose (RP2D)	To evaluate RP2D of TQB2916 injection in Chinese adult patients with advanced solid tumors	Baseline up to 52 weeks
Secondary	Adverse events (AE) , serious adverse events (SAE) and treatment-related adverse events (TRAE)	The occurrence of all adverse events (AE), serious adverse events (SAE) and treatment-related adverse events (TRAE)	Baseline up to 104 weeks
Secondary	Tmax	Time to reach maximum (peak) plasma concentration following drug administration	(-1 to 0 hour) (pre-dose), 0,1, 2, 4, 8, 24, 48,72,144,312,480 hours after intravenous injection of Cycle 1/3 Day 1; In 1 hour before intravenous injection on Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1 and Cycle 8 Day 1.
Secondary	Maximum (peak) plasma drug concentration (Cmax)	Cmax is the maximum plasma concentration of TQB2916.	(-1 to 0 hour) (pre-dose), 0, 1, 2, 4, 8, 24, 48,72,144,312,480 hours after intravenous injection of Cycle 1/3 Day 1; In 1 hour before intravenous injection on Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1 and Cycle 8 Day 1.
Secondary	Elimination half-life (t1/2)	t1/2 is time it takes for the blood concentration of TQB2916 or metabolite(s) to drop by half.	(-1 to 0 hour) (pre-dose), 0, 1, 2, 4, 8, 24, 48,72,144,312,480 hours after intravenous injection of Cycle 1/3 Day 1; In 1 hour before intravenous injection on Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1 and Cycle 8 Day 1.
Secondary	Area under the plasma concentration-time curve from time zero to time t (AUC0-t)	To characterize the pharmacokinetics of TQB2916 by assessment of area under the plasma concentration time curve from the first dose to infinity.	(-1 to 0 hour) (pre-dose), 0, 1, 2, 4, 8, 24, 48,72,144,312,480 hours after intravenous injection of Cycle 1/3 Day 1; In 1 hour before intravenous injection on Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1 and Cycle 8 Day 1.
Secondary	Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)	Cmax is the maximum plasma concentration of TQB2916	(-1 to 0 hour) (pre-dose), 0, 1, 2, 4, 8, 24, 48,72,144,312,480 hours after intravenous injection of Cycle 1/3 Day 1; In 1 hour before intravenous injection on Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1 and Cycle 8 Day 1.
Secondary	Concentration at the end of the dosing interval AUCtau,ss	To characterize the pharmacokinetics of TQB2916 by assessment of area The concentration at the end of the administration interval	(-1 to 0 hour) (pre-dose), 0, 1, 2, 4, 8, 24, 48,72,144,312,480 hours after intravenous injection of Cycle 1/3 Day 1; In 1 hour before intravenous injection on Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1 and Cycle 8 Day 1.
Secondary	Minimum steady-state plasma drug concentration during a dosage interval (Css-min)	Cmin is the minimum plasma concentration of TQB2916	(-1 to 0 hour) (pre-dose), 0, 1, 2, 4, 8, 24, 48,72,144,312,480 hours after intravenous injection of Cycle 1/3 Day 1; In 1 hour before intravenous injection on Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1 and Cycle 8 Day 1.
Secondary	Progress Free Survival (PFS)	Time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first	up to 96 weeks
Secondary	Disease control rate (DCR)	Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD).	up to 96 weeks
Secondary	Duration of Response (DOR)	The time when the participants first achieved complete or partial remission to disease progression.	up to 96 weeks
Secondary	Overall survival (OS)	the time from start of study treatment to date of death due to any cause	up to 96 weeks