A Clinical Trial on the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TQB3019 Capsule in Subjects With Advanced Malignant Tumors

Official title

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TQB3019 Capsules in Subjects With Advanced Malignant Tumors

Overview

The trial was divided into two phases: dose escalation and dose expansion. The dosing regimens were single-dose study and continuous dosing study. A single-center, open, non-randomized, single-arm clinical trial design was adopted. Subjects with advanced malignant tumors were selected to take TQB3019 capsules orally to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of TQB3019 capsules.

Interventions

• Drug TQB3019 capsules
  TQB3019 capsule is a targeted protein degrader

Primary outcome measures

• Dose Limiting Toxicity (DLT) [Time frame: At the end of Cycle 1 (Each cycle is 28 days)]
• Maximum tolerated dose (MTD) [Time frame: At the end of Cycle 1 (Each cycle is 28 days)]
• Recommended Phase II Dose (RP2D) [Time frame: Baseline up to 24 months]
• Maximum assessed dose (MAD) [Time frame: Baseline up to 24 months]
• Adverse events (AEs) [Time frame: From the time the subject receives TQB3019 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years)]
• Serious adverse events (SAEs) [Time frame: From the time the subject receives TQB3019 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years)]
• Abnormal incidence of laboratory test indicators [Time frame: From the time the subject receives TQB3019 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years)]
• Overall response rate (ORR) [Time frame: From date of the first dose until the date of first documented progression or date of death from any cause, up to approximately 3 years]

Secondary outcome measures (12)

• Tmax [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle 1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Cmax [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Elimination half-life (t1/2) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Area under the plasma concentration-time curve from time zero to time t (AUC0-t) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Apparent clearance (CL/F) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Apparent volume of distribution (Vd/F) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Minimum concentration (Cmin) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Bruton's tyrosine kinase (BTK) protein levels [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Complete Remission Rate (CRR) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Disease Control Rate (DCR) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]
• Duration of Response (DOR) [Time frame: From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100weeks]
• Progression Free Survival (PFS) [Time frame: Single Day1/First dose: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 hours post dose Cycle1 Day 8, 15, 28: pre-dose; 0.5, 1, 2, 4, 6, 8, 12, 24 hours at days 28 post dose, each cycle is 28 days]

Eligibility criteria

Inclusion criteria

• Subjects voluntarily joined the study, signed informed consent form, and with good compliance.
• ≥18 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 World Health Organization (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 National Medical Products Administration (NMPA) approved drug instructions;
• Previously received treatment with drugs similar to TQB3019 capsules;
• Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage (investigator judgment)
• Study treatment related: subjects received live or messenger RNA (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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 15 centers

• Cancer Institute & Hospital.Chinese Academy of Medical Sciences — Beijing
• Nanfang Hospital of Southern Medical University — Guangzhou
• The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital — Zhengzhou
• Jiangsu Province Hospital — Nanjing
• The First Affiliated Hospital of Nanchang University — Nanchang
• The First Affiliated Hospital of Xi'an Jiaotong University — Xi'an
• Heze Municipal Hospital — Heze
• The Cancer Hospital Affiliated to Shandong First Medical University — Jinan
• … and 7 more centers

Identifiers

NCT: NCT06943677 · TQB3019-I-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗