A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of TQB3217 Tablets in Subjects With Advanced Malignant Tumors

Official title

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of TQB3217 Tablets in Subjects With Advanced Malignant Tumors

Overview

This is the first-in-human clinical study of TQB3217, aiming to evaluate the safety, tolerability, and pharmacokinetic characteristics of TQB3217 in advanced solid tumors, and to preliminarily explore its efficacy in solid tumors.

Interventions

• Drug TQB3217Tablets
  TQB3217 Tablets are ubiquitin specific peptidase 1(USP1)-t inhibitor.

Primary outcome measures

• Dose Limiting Toxicity (DLT) [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• Maximum tolerated dose (MTD) [Time frame: At the end of Cycle 1 (each cycle is 21 days)]
• Recommended Phase II Dose (RP2D) [Time frame: Baseline up to 24 months]

Secondary outcome measures (12)

• Numbers of participant with Adverse events (AEs) and serious adverse events (SAEs) [Time frame: 30 days after the last administration]
• Time to Reach the Maximum Plasma Concentration (Tmax) [Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5，2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)]
• Peak concentration (Cmax) [Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5，2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)]
• Half-life (t1/2) [Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5，2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)]
• Area under the concentration-time curve (AUC [0-infinity] [Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5，2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)]
• Area under the concentration-time curve (AUC [0-t] [Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5，2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)]
• Apparent clearance (CL/F) [Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5，2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)]
• Apparent Volume of Distribution during the Terminal Phase [Time frame: Single dose day 1: pre-dose, at 0.5, 1, 1.5，2, 3, 4, 6, 8, 12, 24, 48, 72 hours post dose. Days 7, 14 and 21 of multiple dosing cycle 1: pre-dose. Day 21 of multiple dosing cycle 1: at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose (21 days a cycle)]
• Objective Response Rate (ORR) [Time frame: Up to 2 years]
• Disease control rate (DCR) [Time frame: Up to 2 years]
• Duration of Response (DOR) [Time frame: Up to 2 years]
• Overall Survival (OS) [Time frame: From start of study treatment up to die ，estimated at two years]

Eligibility criteria

Inclusion criteria

• Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study;
• Gender is not restricted; Age: 18 to 75 years old; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; expected survival period ≥ 3 months;
• Patients with histologically or cytologically confirmed advanced malignant solid tumors that have failed standard treatment (disease progression or intolerance) or for which there is no standard treatment plan;
• The main organs function well;
• Women of childbearing age should take effective contraceptive measures during the study and within 6 months after the end of the study; serum or urine pregnancy test must be negative within 7 days before enrollment, and they must be non-lactating subjects; men must agree to take effective contraceptive measures during the study and within 6 months after the end of the study.

Exclusion criteria

• History of other malignant tumors within 3 years prior to the first administration of the study drug;
• Has multiple factors affecting oral medication;
• Unalleviated toxicity ≥ grade 1 above CTCAE v5.0 due to any previous therapy, excluding hair loss;
• Major surgical treatment, open biopsy and obvious traumatic injury were performed within 28 days before the study, or have not fully recovered from previous surgery, or are expected to require major surgical surgery during the study period;
• Arteriovenous thrombotic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism;
• Patients who have epilepsy and need treatment or have a history of epileptic seizures, consciousness disorders or unexplained coma within the last 12 months;
• Have a history of psychotropic drug abuse and can not quit or have mental disorders;
• Subjects with any severe and / or uncontrolled disease;
• Has known symptomatic central nervous system metastases and/or cancerous meningitis;
• Presence of massive serous pleural/abdominal/pericardial effusion with clinical symptoms or requiring repeated drainage.
• Has participated in other clinical trials within 4 weeks before first dose;
• Receipt of chemotherapy or immunotherapy within 4 weeks before the first administration;, Receipt of radiotherapy or small molecule targeted drugs within 2 weeks, or are still within 5 half-lives of the drugs;
• Receipt of Chinese patent medicines explicitly indicated for anti-tumor use in their drug labels approved by National Medical Products Administration (NMPA) within 2 weeks prior to the first administration;
• According to the judgement of the investigators, Subjects who are at risk of active bleeding during the trial period.

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 · 1 center

• National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Uni — Beijing

Identifiers

NCT: NCT07291050 · TQB3217-I-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗