A Phase Ib Clinical Study to Evaluate the Efficacy and Safety of of TQB2618 Injection Monotherapy and Combination Regimen (With Penpulimab Injection ±Anlotinib Hydrochloride Capsules) in the Four or Later Lines of Treatment of Advanced Colorectal Cancer.
Overview
- Phase
- Phase 1
- Intervention
- TQB2618 injection
- Conditions
- Colorectal Cancer
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 75
- Locations
- 15
- Primary Endpoint
- Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase Ib clinical study to evaluate the efficacy and safety of TQB2618 injection as monotherapy and a combination regimen (with Penpulimab injection ± Anlotinib hydrochloride capsules) in the treatment of advanced colorectal cancer. 75 participants will be enrolled in the study. Objective response rate (ORR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 is the primary endpoint.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-1; Expected survival of more than 3 months;
- •Histologically/cytologically confirmed metastatic colorectal cancer;
- •The subjects should provide tumor tissues that meet the requirements for mismatch repair protein detection and Programmed cell death-Ligand 1 (PD-L1) expression level detection;
- •Advanced colorectal cancer that progresses or is intolerant after receiving ≥3 lines of standard therapy;
- •Failure of treatment with at least one of these drugs (TAS-102, Regorafenib, Fruquintinib);
- •Confirmed presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) criteria;
- •Body weight ≥40 kg and Body Mass Index (BMI) ≥18.5 kg/m\^
- •The function of the main organs is good, and the laboratory examination meets the requirements;
- •Female subjects of reproductive age should agree to use contraception during the study period and for 6 months after the end of the study; Male subjects should agree that contraception must be used during the study period and for 6 months after the end of the study period.
Exclusion Criteria
- •Have had or are currently suffering from other malignant tumors within 3 years;
- •Have any poorly controlled cardiovascular clinical symptoms or diseases;
- •Patients with ulcerative colitis and Crohn's disease; Patients with active inflammatory bowel disease within the first 4 weeks of enrollment;
- •Symptoms of hematemesis and hematochezia occurred within 6 months before screening, and the daily bleeding volume ≥ 2.5 mL;
- •The presence of unmitigated toxic reactions of grade 1 or above as assessed per Common Terminology Criteria for Adverse Events (CTC-AE) due to any treatment prior to first administration, excluding hair loss;
- •Patients who had received Programmed Death 1 (PD-1) or PD-L1 monoclonal antibody treatment and experienced ≥ grade 3 immune-related adverse reactions or stopped immune checkpoint inhibitor treatment due to immune-related adverse reactions;
- •Active or uncontrolled severe infection (≥CTC AE grade 2 infection);
- •Decompensated cirrhosis, active hepatitis;
- •Poor diabetes control (fasting blood glucose \> 10 mmol/L);
- •Patients with renal failure requiring hemodialysis or peritoneal dialysis;
Arms & Interventions
TQB2618 injection+Penpulimab injection +Anlotinib hydrochloride capsules
TQB2618 injection combined with Penpulimab injection and Anlotinib hydrochloride capsules, 3 weeks as a treatment cycle.
Intervention: TQB2618 injection
TQB2618 injection+Penpulimab injection +Anlotinib hydrochloride capsules
TQB2618 injection combined with Penpulimab injection and Anlotinib hydrochloride capsules, 3 weeks as a treatment cycle.
Intervention: Penpulimab injection
TQB2618 injection+Penpulimab injection +Anlotinib hydrochloride capsules
TQB2618 injection combined with Penpulimab injection and Anlotinib hydrochloride capsules, 3 weeks as a treatment cycle.
Intervention: Anlotinib hydrochloride capsules
TQB2618 injection+Penpulimab injection
TQB2618 injection combined with Penpulimab injection, 3 weeks as a treatment cycle.
Intervention: TQB2618 injection
TQB2618 injection+Penpulimab injection
TQB2618 injection combined with Penpulimab injection, 3 weeks as a treatment cycle.
Intervention: Penpulimab injection
TQB2618 injection
TQB2618 injection, 3 weeks as a treatment cycle.
Intervention: TQB2618 injection
Outcomes
Primary Outcomes
Objective response rate (ORR)
Time Frame: From first administration until disease progression or withdrawal due to other reasons, estimated to not exceed 8 months.
According to RECIST 1.1 or Modified RECIST 1.1 for immune based therapeutics, (iRECIST) criteria, the proportion of subjects whose confirmed tumor volume reduction reached the pre-specified value and maintained the minimum time-frame requirements, i.e., the proportion of subjects with complete response (CR) and partial response (PR).
Secondary Outcomes
- Duration of response (DOR)(From first administration to the time of disease progression or death from any cause, estimated to not exceed 12 months.)
- Anti-drug antibodies (ADA)(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, 30 days and 90 days after the last dose. Each cycle is 21 days.)
- Neutralizing antibodies (NaB)(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, 30 days and 90 days after the last dose. Each cycle is 21 days.)
- Progress free survival (PFS)(From randomization to the time of disease progression or death from any cause, estimated to not exceed 12 months.)
- Disease control rate (DCR)(From first administration to the time of disease progression or withdrawal from any cause, estimated to not exceed 12 months.)
- The incidence of adverse event (AE)(From first administration to 28 days after withdrawal or the start time of the new anti-tumor treatment, whichever comes first.)
- Overall survival (OS)(Baseline up to death, estimated to not exceed 12 months)